University of Ghana http://ugspace.ug.edu.gh DEPARTMENT OF POPULATION, FAMILY AND REPRODUCTIVE HEALTH SCHOOL OF PUBLIC HEALTH COLLEGE OF HEALTH SCIENCES UNIVERSITY OF GHANA DETERMINANTS OF ADHERENCE AND TREATMENT OUTCOMES AMONG ADOLESCENTS LIVING WITH HIV IN CAMEROON BY MBUWIR CHARLOTTE BONGFEN (10600726) THIS THESIS IS SUBMITTED TO THE UNIVERSITY OF GHANA, LEGON IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE AWARD OF PHD DEGREE IN PUBLIC HEALTH JULY 2019 University of Ghana http://ugspace.ug.edu.gh DECLAR\TIO' I hereby declare that this thesis is the product of my original independent resean:h wnuw:leJ in selected health facilities in the North West and South West Regions of Cameroon under the supervision of Professor Kwasi Torpey, Professor Augustine Ankomah, and Dr. John Ganle. I confirm that this thesis has not been published or submitted to any institution lor any academic award. All references made to other researchers' works have been duly acknowledged. Mbuwir Charlotte Bongfen 4.::f (D ~\ bl.Dt2D (PhD Candidate) Date Signature TEA,\1 OF Sl!PERVISORS Professor Kwasi Torpey (Principal Supervisor) Date Signature Professor Augustine Ankomah ( Co-Supervisor) Date Signature Dr Ganle john (Co-Supervisor) University of Ghana http://ugspace.ug.edu.gh DEDICATION This piece of work is dedicated to all adolescents who are HlV positive. It is also dedicated to my daughters Sunjo Brielle Kefiyki and Sunjo Kendra Vernyuy, my dear husband Dr. Tata Emmanuel Sunjo, my parents; Mbuwir Abel Kavwo and Yunkung Flora Bonglam, and my Sister; Mbuwir Brida Verwiyni. ii University of Ghana http://ugspace.ug.edu.gh ACKNOWLEDGEMENTS My heartfelt gratitude goes to my supervisors Professor Kwasi Torpey, Professor Augustine Ankomah, and Dr John Ganle, for their support and professional directives that have seen the completion of this work. My sincere gratitude also goes to the lecturers of the School of Public Health and the Department of Population, Family and Reproductive Health, in particular, for the knowledge and academic guidance I have received from them throughout my study period. I am also indebted to the European Union for their scholarship award through the Partnering for Health Professional Training in Africa (P4HPT) project. It is thanks to the financial assistance from this scholarship programme that I was able to enrol and complete the PhD programme in the School of Public Health at the University of Ghana. Special thanks to all the adolescents who participated in this study. I also acknowledge with profound gratitude my research assistants, Wam Joel and Bessong Sarriete. My gratitude also goes to Kidzeru Therese (Aunty Yaya), Banin Rosette, Atanga Anye Louis and Tankoh Marceline for their sacrifices and efforts throughout the data collection period. My appreciation also goes to my sister, Mbuwir Brida, for all her support throughout my study period. I also accord sincere thanks to my husband, Dr. Tata Emmanuel Sunjo; my children. Sunjo Brielle and Sunjo Kendra; my parents, Mbuwir Abel and Yunkung Flora, the Yunkungs Family, the Badzi's family and all my friends for their moral support throughout my study and stay in Ghana. Finally, I am most grateful to the Almighty God for all the wonderful things he has done and continues to do in my life. iii University of Ghana http://ugspace.ug.edu.gh TABLE OF CONTENTS DECLARATION ..................... . .............................. . ................................ DEDICATION ............................ ....... . ............................. . .. ............................. ii ACKNOWLEDGEMENTS ................................................ . . .................................. .iii TABLE OF CONTENTS ................... ····························· ..................................... iv LIST OF TABLES .............................................. . ................................... viii LIST OF ABBREVIATIONS ....................... .............. . .. ....................................... .x i DEFINITION OF KEY TERMS ............................. . . ................................... .x ii ABSTRACT ........................ · .... ·· .. ··· .. ·. ... · .. ·· .. ·· .. ····· ......................................... xiii CHAPTER ONE .......................................... ............ . ...................................... .. INTRODUCTION .............................................. . . ........................................................ 1 1.0 Background ...................................... . .......................................................... 1 1. I Problem Statement ........................... ········ .. ...................................................... 4 1.2 Research questions.......................... . ................................................................... 7 1.3 Objectives............... ....................... .. ..................................................... 7 1.3.1 General objective ...................... . .. ........................................................ 7 1.3.2 Specific Objectives....................... . .................................................... 8 1.4 Research Hypotheses ........................................ .................................................... 8 1.5 Justification ................................................................................................................ 8 1.6 Chapter summary and thesis outline ......................................................................... 10 CHAPTER TWO ................................................................................................................ 11 LITERATURE REVIEW ................................................................................................. 11 2.0 Introduction ............................................................................................................... 11 2.1 The concept of adolescence ...................................................................................... 11 2.2 HIV and adolescence ................................................................................................. 14 2.3 The Concept of Adherence ........................................................................................ 16 2.4 Adherence to ART .................................................................................................... 18 2.5 Consequences of Poor Adherence ............................................................................. 21 2.6 Adolescents living with HIV ..................................................................................... 22 2.7 Adherence to ARV among adolescents ..................................................................... 25 2.8 Treatment Outcomes ................................................................................................. 27 2.8.1 Viral load suppression ........................................................................................ 27 2.8.2 Lost to follow up (LTFU) .................................................................................. 29 2.8.3 Retention ............................................................................................................ 30 2.8.4 CD4 Counts ........................................................................................................ 30 2.8.5 Mortality ............................................................................................................. 31 2.9 Adolescents' perspectives on HIV and ART adherence ........................................... 33 2.10 Challenges to Adherence ......................................................................................... 34 2.10.1 Individual factors ............................................................................................. 35 2.10.2 Medication Factors ........................................................................................... 35 2.10.3 Health Service factors ...................................................................................... 36 2.10.4 Socio-economic Factors ................................................................................... 36 iv University of Ghana http://ugspace.ug.edu.gh 2.11 Detenninants of Adherence to Anti-Retroviral Therapy among adolescents ......... 37 2~. :1; ~T~:~?:~~.~~":~~· ..........· •• ·· · •• ·.•: •• • ·•·· ...••· .... .· •••• •••••••.•••••••.••..•• ~~ 2.11 .1 .4 Distance to Health Facility ......................................... ······························· 39 2.:i~21;~!i~~~~~:i·f~~~~;~·:::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::~: 2.11.2.1 Use of traditional medicines ..................................................................... .40 2.11.2.2 Beliefs in Spiritual Healing ...................................................................... .40 2.11.3 Health Services and System Factors ................................................................ 41 2.11.4 Patient factors ............................................................ ················ .. ······ .... · .. ·· .. ···· 41 2.11.4.1 Medication related side effects ................................... ··.·· ......................... 42 2.11.4.2 Internalized stigma .................................................................................... 45 2.11.4.3 Other illnesses or comorbid conditions ................................................... .46 2.11.5 Other factors ..................................................................................................... 47 2.11.5.1 Stigma ....................................................................................................... 48 2.11.5.2 Forgetting to take medications ................................................................. .49 2.11.5.3 Financial constraints ................................................................................ .49 2.11.5.4 Pill Burden ................................................................................................ 50 2.12 Care of adolescents and health facility preparedness towards providing ART services ............................................................................................................................ 51 2.12.1 Care of Adolescents with HIV at the facility level .......................................... 51 2.12.2 Health facility preparedness in Providing ART services to adolescents with HIV .............................................................................................................................. 55 2.13 Strategies to improve adherence to ART among adolescents ................................. 57 2.14 Global Response to the HIV epidemic among adolescents .................................... 68 2.15. Measurement issues in adherence research ............................................................ 69 2.15.1 Self-Reporting .................................................................................................. 70 2.15.2 Pill counts ......................................................................................................... 71 2.15.3 Phannacy Refill Records .................................................................................. 71 2.15.4 Therapeutic Drug Monitoring .......................................................................... 72 2.15.5 Composite Measures ........................................................................................ 73 2.16 Philosophical Underpinnings of the Conceptual Framework ................................. 73 2.17 Conceptual Framework ........................................................................................... 75 2.18 Chapter summary .................................................................................................... 77 CHAPTER THREE ............................................................................................................. 78 METHODS ......................................................................................................................... 78 3.0 Introduction ............................................................................................................... 78 3.1 Type ofStudy/Study design ...................................................................................... 78 3.2 Study Location/Area ................................................................................................. 78 3.2.1 Location of the study Area ................................................................................. 81 3.2.3 Socio-Demographic Characteristics ................................................................... 83 3.2.4 Economic Activities ........................................................................................... 84 v University of Ghana http://ugspace.ug.edu.gh 3.2.5 Healthcare Services and Infrastructure .............................................................. 85 3.7 Data Collection Methods and Tools ............................................... ········ ................... 92 3.7.1 Data collection methods ............................................................ ····· .................... 92 3.7.2 Data Collection tools ................................................................ · ......................... 93 3.83~~~~=:~~~::::c~~i~~~~·::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::: ~~: 3.8 2 Pre-testing of questionnaire ............................................................................. 105 3.9 Data entry and processing ......................................................... ·.·.·· .. · .... ·· ............... 105 3.10 Variables and measurement .................................................................................. 105 3.10.1 Adherence ...................................................................................................... 106 3.10.2 Treatment outcomes ........................................................... ··.· .. ···· .................. 10 6 3.10.3 Patient factors ........................................................................... ·· .................... 107 3. t 0.4 Health Service factors .................................................................................... 108 3.10.5 Socio-cultural factors ..................................................................................... 108 3.10.6 Demographic factors ...................................................................................... 108 3.10.7 Other factors ................................................................................................... 109 3.10.8 Statistical Methods ......................................................................................... 109 3.11 Ethical Considerations/Issues ................................................................................ 110 3.11.1 Administrative and Ethical Approval.. ........................................................... 110 3. t 1.2 Informed consent. ........................................................................................... 111 3.11.3 Informed ascent. ............................................................................................. 111 3.11.4 Confidentiality ............................................................................................... 112 3.11.5 Privacy ........................................................................................................... 112 3.11.6 Benefits .......................................................................................................... 112 3.11.7 Risks ............................................................................................................... 112 3.11.8 Right to withdraw ........................................................................................... 113 3.12 Chapter Summary .................................................................................................. 113 CHAPTER FOUR ............................................................................................................ 114 RESULTS ........................................................................................................................ 114 4.0 Introduction ............................................................................................................. 114 4.1 Demographic Characteristics of Participants .......................................................... 114 4.2 Clinical Characteristics ........................................................................................... 116 4.3 Trends in yearly enrolment of participants into treatment ...................................... 118 4.4 Distribution of Adolescents by Facility .................................................................. 119 4.5 ARV Adherence levels ............................................................................................ 120 vi University of Ghana http://ugspace.ug.edu.gh 4.5.1 Self- Report ARV Adherence .......................................................................... 120 4.5.2 Medication Possession Ratio (MPR) .............................................................. 120 4.6 Detenninants of Adherence .................................................. ·. ... ·· ............................ 122 4.6.1 Socio-demographic factors and Adherence ..................................................... 122 4.6.2 Health Service factors ...................................................................................... 125 4.3.3 Socio-cultural factors and Adherence .............................................................. 126 4.6.4 Patient Factors and Adherence ......................................................................... 128 4.6.5 Other factors of Adherence .............................................................................. 131 4.7 Multivariate analysis of the determinants of adherence ........................... · .......... ·· .. 132 4.8 Detenninants of both self-report and the Medication Possession Ratio adherence 135 4.9 Challenges of Adherence among Adolescents ........................................................ 135 4.10 Improving Adherence among Adolescents ........................................................... 137 4.11 Adolescents HIV Treatment Outcomes ................................................................ 139 4.11.1 Measures of viral load ....................................... · .. · ...... · .......... · ...... · .... """. ..... 139 4.11.2 Relationship between Adherence and Viral load ........................................... 140 4.12 CD4 Measurements ............................................................................................... 140 4.13 Retention rates .................................................................... · .. ·········· ...................... 141 4.13.1 Retention rates at six months ......................................................................... 142 4.13.2 Retention Rates at 12 months .......................................... · ...... · ...................... 143 4.13.3 Retention Rates at 24 months ......................................................................... 144 4.14 Facility Preparedness towards Care of Adolescents ............................................. 146 4.14.1 Adherence by Health Facility Score .............................................................. 149 4.15 Chapter Summary .................................................................................................. 150 CHAPTER FIVE ............................................................................................................... 151 DISCUSSION ................................................................................................................... 151 5.0 Introduction ............................................................................................................. 151 5.1 Clinical characteristics of participants .................................................................... 151 5.2 Adherence level among adolescents ....................................................................... 152 5.3 Detenninants of adherence among adolescents ...................................................... 154 5.4 Challenges of Adherence in adolescents ................................................................. 163 5.5 Adolescent's perspective on adherence .................................................................. 166 5.6 Improving adherence among adolescents ............................................................... 168 5.7 Treatment outcomes among adolescents with HIV ................................................ 170 5.8 Facility preparedness towards care of adolescents ................................................. 172 ~11~§~;£tl~~::::::::::::::::::::::::::··:···:::·::::::::::::::::::::::::::::::::::::::::::::: m ~~~~~::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::~~~ vii University of Ghana http://ugspace.ug.edu.gh LIST OF TABLES Table 1 Recommendations for starting ARVs in adolescents and Adults in Cameroon .... 55 Table 2 Number of Adolescents on treatment in the selected Health Facilities ................. 91 Table 3: Scoring Summary of the lSI Too!... .................................. ···.············ .................. 104 Table 4: The Kappa benchmark scale ............................................................................... 110 Table 5: Socio-demographic Characteristics of Participants ............................................ 115 Table 6 Clinical Characteristics of Participants by Sex .................................................... 117 Table 7 ARV drug types used by participants with their code names .............................. 118 Table 8 Relationship between Self-Report adherence measure and Medication Possession Ratio ., .................................................................................. 122 Table 9 Relationship between adherence and socio-demographic factors ........................ 124 Table 10: Health Service Factors and Adherence ............................................................. 126 Table II Relationship between Socio-cultural factors and Adherence among Adolescents. 127 Table 12 Relationship between Patient Factors and Adherence ....................................... 130 Table 13: Other Determinants of Adherence .................................................................... 131 Table 14 Relationship between Adherence and its Detem1inants in Multiple Logistic Regression Analysis .................................................................................... 133 Table 15: Determinants of both self-report and the Medication Possession Ratio adherence 136 Table 16 Challenges of Adherence faced by the Adolescents .......................................... 137 Table 18 Relationship between Viral load suppression and Adherence ........................... 140 Table 19 Relationship between Adherence and CD4 among adolescents ........................ 141 Table 20 Retention rates at 6 months ................................................................................ 142 Table 21: Retention Rates at 12 months ........................................................................... 143 Table 22: Retention Rates at 24 months ........................................................................... 145 Table 23: Health Facility Readiness to provide care to adolescents ................................. 147 Table 24: Health Facility Score and Interpretation of Score ............................................ 149 viii University of Ghana http://ugspace.ug.edu.gh LIST OF FIGURES Figure 1: New HIV infections globally 2000-2016 among Adolescents (1 0-19 years) ..... 23 Figure 2. Global distribution of number of adolescents aged 10-19 years living with HIV by country in 2014 ...................................................................................... 24 Figure 3. Proportion of adolescents aged 10 - 19 living with HIV. by selected high-burden countries 2014. ........................................................................................ 24 Figure 4: Total AIDS related deaths and deaths in adolescents .......................................... 31 Figure 5: Conceptual framework ........................................................................................ 76 Figure 6. Map of Cameroon showing North West and South West Regions ..................... 79 Figure 7: Map of the North West and South West Regions showing the Study Sites within the Health Districts .......................................................................................... 82 Figure 8: The distribution of adolescents by year enrolled into treatment ....................... 119 Figure 9: Participant distribution according to health facility .......................................... 119 Figure 10: Percentage distribution of participants by Self-Report Adherence ................. 120 Figure II: Adolescents Adherence levels using the MPR Measure ................................. 121 Figure 12: Participant's perspective on improving adherence .......................................... 138 Figure 13: Viral load suppression among Adolescents ..................................................... 139 Figure 14: Measures ofCD4 count ................................................................................... 141 Figure 15: Retention rates per Health Facility .................................................................. 145 Figure 16: Adherence by Facility Score ............................................................................ 150 ix University of Ghana http://ugspace.ug.edu.gh LIST OF APPENDICES Appendix I: Invitation to Participate in PhD Research .................................................... 202 Appendix 2: Participant Information Sheet for adolescents at least 18years .................... 203 Appendix 3: Written consent form for Adolescents at least 18years ................................ 204 Appendix 4: Infonnation sheet for Guardian .................................................................... 205 Appendix 5: Written Consent form for Guardian ............................................................. 207 Appendix 6: Information Sheet for adolescents less than 18years ................................... 208 Appendix 7: Written assent form for Adolescents less than 18years ................................ 210 Appendix 8: Questionnaire ............................................................................................... 211 Appendix 9: Data Extraction form for Adolescents on ARV treatment ........................... 218 Appendix 10: Research Approval Letter from the North West Regional Delegation of Public Health ......................................................................................................... 222 Appendix 11: Research Approval Letter from the West West Regional Delegation of Public Health ......................................................................................................... 223 Appendix 12: Ethical Approval Letter from Cameroon Baptist Convention Institutional Review Board ...................................................................................... 224 Appendix 13: Letter of Support for Ethical Clearance Application ................................. 226 x University of Ghana http://ugspace.ug.edu.gh LIST OF ABBREVIATIONS ACTG AIDS Clinical Trial Group ALHIV Adolescents Living with HIV ART Antiretroviral Therapy ARV Anti -retroviral BBH Banso Baptist Hospital BHM Baptist Hospital Mutengene BRH Buea Regional Hospital BUCREP Central Bureau of Census and Population studies CAMPHIA Cameroon Population-Based HIV Impact Assessment CASE Centre for Adherence Support Evaluation CBC Cameroon Baptist Convention CBOs Community Based Organisations CDC Centre for Disease Control and Prevention HIV Human Immunodeficiency Virus lAS International AIDS Society JSI John Snow Inc KDH Kumba District Hospital LRH Regional Hospital Limbe LTFU Lost to Follow Up MIS Management Information System MPR Medication Possession Ratio NACO National AIDS Control Organisation NBH Nkwen Baptist Hospital NGOs Non-governmental Organisation RHB Regional Hospital Bamenda RTG Regional Technical Group SARA Service Availability and Readiness Assessment UNAIDS United Nations AIDS Programme VCT Voluntary Counselling and Testing WHO World Health Organisation xi University of Ghana http://ugspace.ug.edu.gh DEFINITION OF KEY TERMS For the purpose of this study, the key terms have been operationally defined as follows: Adolescents: An individual who is aged between 10-19years. Young adolescence: A period of an individual's life when they are aged 10-14years. M idd Ie adolescence: A period of an individual's life when they are aged 15-17years. Late adolescence: A period of an individual's life when they are aged 18-19years. Self-Report Adherence: The proportion of the number of pills taken to the number prescribed within the past 30 days. Viral load suppression: Having a viral load count less than 1000copies/ml of blood. Determinants of adherence: The factors that undermine or facilitate one's ability to take prescribed medication. Medication Possession Ratio: The sum of the days of treatment supplied for all Anti- retroviral prescriptions filled, within the refill interval to the number of days during that same time interval. xii University of Ghana http://ugspace.ug.edu.gh ABSTRACT Background: Despite over three decades of HIV, its prevalence especially among adolescents remains a public health concern. In 2015, there were more than two million adolescents living with HIV, with a higher proportion coming from sub-Sahara Africa. In Cameroon, there are over 40,000 adolescents living with HIV and there are still concerns about the provision of care to them as adolescents are trapped between paediatric and adult services which are unable to address their specific needs. However, there are limited studies in Cameroon that have examined adherence to antiretroviral treatment and associated factors as well as treatment outcomes among adolescents. It is therefore essential to clearly understand the detenninants of adherence oft hese adolescents and their treatment outcomes. Objectives: The main objective of the study was to assess the determinants of adherence to Anti-Retroviral Therapy and treatment outcomes among adolescents living with HIV in Cameroon. Methods: The study was an analytical cross-sectional sStudy with a record review component. A total of 460 respondents were recruited from nine health facilities. A systematic random sampling procedure was used to select the required participants. Pre- tested questionnaires were administered to participants to collect data. The main outcome of interest (adherence) was measured in two ways: self-report adherence, and medication possession ratio (MPR). Three treatment outcome measures that were assessed included viral load suppression, retention in treatment, and CD4 counts. Finally, health facility readiness towards care for adolescents on ARV was assessed using the John Snow Inc. (JSI) tool. Descriptive (frequencies and proportions) and inferential (chi square and multivariate logistic regression) statistical analyses methods were used to analyse the data. Statistical significance was set at p<0.05 at a 95% confidence level. xiii University of Ghana http://ugspace.ug.edu.gh Results: A total of 455 questionnaires were retained and this gave a response rate of 99%. The average age of the adolescents was 14.8years (SD= ±2.9years). There were more females (55%) than males (45%) in the study. A larger proportion of the respondents were on first line treatment (77%) and had been on treatment for an average of five years. Self- report adherence was 83% while MPR was 73%. The difference in adherence between self- report and the Medication Possession ratio was not statistically significant (p=0.97). Regarding the determinants of adherence, 12 out of 30 independent variables examined showed significant statistical association with adherence at the bivariate level. In multivariable logistic regression analyses however, only two variables significantly predicted adherence, namely experiencing side effects (AOR= 2.63; 95%CI=1.14, 6.09; p = 0.02) and internalized stigma (AOR=2.51; 95%CI =1.04, 6.04; P = 0.04). The major challenges to adherence were stigma (59%) and forgetfulness to take medications (59%) while sending reminder messages and having friendlier health providers were the main suggestions to help improve on adherence. In terms of treatment outcomes, 70% of the respondents had their viral load suppressed. The retention rates were observed to decrease over time: 88%, 72% and 58% at 6months, 12 months and 24 months respectively. All the selected facilities were shown to be ready to receive adolescents into treatment as 7 out of the 9 facilities were in stage 5 of the facility readiness assessment. Conclusion: The determinants of adherence among adolescents are more psychological than the physical characteristics that differentiate them. There is therefore a need for more individual-targeted counselling for adolescents and their guardians to improve adherence levels among adolescents on antiretroviral treatment. Keywords: Adolescents, adherence, determinants, Anti-retroviral, treatment outcomes, stigma, side effects, viral load suppression, retention. xiv University of Ghana http://ugspace.ug.edu.gh CHAPTER ONE INTRODUCTION 1.0 Background The 2l't Century has witnessed several epidemics on a global scale; yet HIV has been one of the longest and severest health challenges facing public health programmes. The United Nations AIDS (UNAID) estimates that in 2018, there were over 37.9 million people living with HIV worldwide (UNAIDS, 2019). The virus has claimed millions of lives and many more are infected every day. UNAID (2016) notes that despite the declining figure of new infections, the number of people living with HIV has continued to rise given that, many of the individuals living with the virus are able to lead longer and healthier lives, mostly as a result of effective antiretroviral therapy (ART). At first, HIV was considered to be a disease of adults, especially those with high risk sexual behaviours (horizontally transmitted) until it was realized that mothers could pass it on to their babies (vertical transmission). The prevention of mother-to-child transmission of HIV interventions became accessible in most countries in Africa around 2004 (Lowenthal et af., 2014). From 2004 to 2017, the cohort of children who were infected through vertical transmission and survived together with many more who acquired the infection through risky sexual behaviours are now Adolescents Living with HIV (ALHIV). Until the early 2000s, the assumption was that, most children born to HIV positive mothers will not live beyond five years (Ferrand et al., 2009). Nevertheless, a cohort study revealed that at least 13% of these children could survive to age 10 years, with more recent estimations showing that 17% of them will survive up to 15 years of age (ibid). Moreover, due to improvements in HIV treatment, mortality in perinatally infected children has University of Ghana http://ugspace.ug.edu.gh declined, thus making it possible for them to live up to adolescence even in the face of the challenges of taking ARVs (Palladino et aI., 2009; Edmonds et a/., 2011). Worldwide, there are over 3 million children infected with HIV and their survival to adolescence indicates that a significant number of them adds to the number of adolescents living with HIV (Lowenthal ef aI., 2014). UNICEF estimates that 700 adolescents are infected with HIV daily and if current trends remain constant, the world will be hosting over 1.9 million adolescents living with HIV by 2030 (UNICEF. 20IS). Generally, young people and adolescents have been more susceptible to HIV infection. By June 2018, it was estimated that, out of the 37.9 million people living with HIV (PLHIV) worldwide, more than 90% were in the global south, with 1.7 million of them being aged less than ISyears (UNAIDS, 2019). Furthermore, in 2013, there were over 6300 new HIV infections everyday globally and about 2S00 of these were adolescents and young people between the aged IS-24years (WHO, 20l3a). In Cameroon, there are 6S,37S youth (IS- 24years) living with HIV and this gives a prevalence of 1.4% among this age group (PEPFAR, 2018a). Therefore, adolescents and youth remain susceptible to having the HIV infection, especially those living in settings with a generalised HIV epidemic (WHO, 2013a). The prevalence ofHIV among adolescence in Cameroon was estimated to be 2% in 2015, with about new 4200 infections and 1900 deaths (UNICEF, 201S). As of2016, a total of about 40,000 adolescents were living with HIV in Cameroon (UNAIDS, 2017b). In spite of this, adolescents are an underserved group in global and national responses to the HIV pandemic. Global declarations, commitments and targets have not given attention to their particular needs (MacPherson et al., 2015; UNICEF, 2015). With the launching of the 2 University of Ghana http://ugspace.ug.edu.gh SDGs, much of the world has focused its attention towards achieving the targets of the Sustainable Development Goals (SDGs), however, the HIV epidemic among adolescents is also a call for concern and it is imperative to hasten up efforts to curbing the epidemic. This is a necessary step focused on ending the HIV epidemic and ensuring that all adolescents have the opportunity to live on (UNICEF, 2015). Adolescence is a time of vibrancy. exploration and self-discovery; it is also a time of rapid and sometimes confusing physical, psychological and emotional changes (UNICEF., 2002). When this is further complicated by an infection like HIV, the adolescent may face more challenges than a non-infected peer. With the high number of adolescents living with HIV, it is imperative to understand the determinants of adherence and the treatment outcome. Adherence is an individual's ability to follow treatment plans, take medications at designated times and frequencies and follow restrictions regarding food and other medications correctly (Sahay, Reddy, & Dhayarkar, 2011a). Moreover, adherence could also be an individual's ability to follow-up all clinic visits (WHO, 2010). Globally, adherence has been estimated to be lower in adolescents than in other age groups (Sung-Hee, Gerver, Fidler, & Ward, 2014). A systematic review by Sung-Hee and others in 2014, reported adherence in adolescents to be 62.3% (Sung-Hee et al., 2014). The treatment of HIV is long and could even last a life time and adherence to medication has been shown to reduce with time. All HIV patients are on daily medication and the process is difficult and monotonous such that after six months, adherence to the medications begin to drop as shown in a study by Nsheha and others in 2014 (Nsheha, Dow, Kapanda, Hamel, & Msuya, 2014). Worldwide. issues of adolescent health are gradually attracting concern and in the case of ALHIV, health facilities are preparing to have the adequate resources to enable them provide 3 University of Ghana http://ugspace.ug.edu.gh care to these HIV positive adolescents. Scaling up of HIV care in developing countries is usually very challenging as it requires increases in terms of infrastructure, human resources and limited drug management systems (Mapunjo, 2007). These factors could possibly affect adherence especially in the case of adolescents who need to be given special attention. Generally, non-adherence increases the chances of virologic failure by 50%, and viral resistance also reduces the effectiveness of treatment, thereby causing the disease to advance and may decrease treatment options in the near future as well as increase the possibility of disease transmission as a result of unsuppressed viral loads (Roux et ai., 2011). Hence, optimal adherence, that is, greater than 95% of pills taken is the key to success in HIV infected children and adolescents who are on long term treatment (Shah, 2007; Arage, Tessema, & Kassa, 2014). It is for this reason that the current study aimed to assess treatment adherence, and the factors that determine treatment adherence and outcomes among adolescents living with HIV in Cameroon. 1.1 Problem Statement Despite over three decades of HIV, its prevalence especially among adolescents remains a public health concern. By 2017, there were over 250,000 new HIV infections among adolescents globally with a higher proportion living in sub-Sahara Africa (UNAIDS, 2019). In Cameroon, UNICEF estimated over 4200 new HIV infections in adolescents by 2015 and by 2016, there were over 40,000 adolescents who had HIV (UNICEF, 2018). In 2012, the prevalence of HIV among adolescents in Cameroon was 2%, and 4000 new infections are anticipated to OCcur annually (UNICEF, 2015). The rising number of HIV positive adolescents is perhaps due to the increase in incidence of horizontally acquired HIV as well as increase in the survival rates of children who acquired the virus through mother to child transmission of HIV (Maskew et al., 2016). 4 University of Ghana http://ugspace.ug.edu.gh Adolescents at their age are faced with challenges that are cognitive and developmental, emotional and sometimes family dysfunction (UNICEf., 2002). Adolescents have for some time been trapped between child and adult services, which do not meet up their particular needs. such as HIV status disclosure, adherence support mechanisms, issues of stigma and discrimination, sexual and reproductive health. mental healthcare, legal and social support (Ferrand et aI., 2009). The situation is not very different in Canleroon where there are thousands of adolescents living with HIV. As a result, adhering to ART treatment has become an important subject. Recent treatment protocol requires early initiation of antiretroviral treatment (ART) with adolescents increasingly being the most initiators of ART (MacDonell, Naar-King, Huszti, & Belzer, 2013). Evidence from research done on adherence to ART among adolescents has shown that. HIV adherence is lower than in adults (WHO, 2013a; Sung-Hee et al., 2014). Adherence among adults in Cameroon is above 90% (Mbuagbaw et al., 2011). However, adherence among adolescents in Cameroon is unknown and hence the need for the present study. Worldwide. there was a 50% rise in HNIAIDS related deaths among young people and adolescents between the age 1O-24years, and this indicates the need for improvements in HIV treatment. care and retention among this age group (Lall, Lim, Khairuddin, & Kamarulzaman. 2015). However, ART drugs are known for their complications with special dosing requirements and side effects (Brogly et al., 2005). Adolescents with HIV face different barriers to adherence from adults (Buchanan et al., 2012). Such barriers (Ibid) include health facility issues, demographic and socio-cultural factors as well as difficulties at the individual level. Moreover, adolescents with HIV have a higher potential for non- adherence to ART due to their biological development which is characterized by reduced 5 University of Ghana http://ugspace.ug.edu.gh inhibition, increased risk-taking, and reduced support from parents or caregiver (Reisner et al., 2009). The PEPF AR strategic report for Cameroon indicates that there are 17,557 youth receiving ARV drugs with an estimated viral load suppression of 69% (PEPFAR, 2018b). This lower viral load suppression is an indication that there are issues relating to adherence to ARV. In this regard, this study sought to assess some of the predictors of adherence, especially as they relate to adolescents with HIV and their adherence to ART in Cameroon. Some scholars have identified health service characteristics as one of the many set of factors that could affect ART adherence (Sung-Hee et al., 2014). In line with these scholars (Ibid), one of these relates to the fact that adolescent's access to health facilities is always limited and they are sometimes marginalised from mainstream healthcare provision. Generally, there is a standard level of quality of care required for the delivering antiretroviral therapy (WHO, 2004b: Gilks et al., 2006) and this is not different for adolescents. In fact, adolescents need to be given special attention. Some of the indicators that are used to measure how prepared a facility is in providing care for living HIV positive persons and in this case adolescents, include organization ofHIVI AIDS care within the facility, availability of human resource and protocols, clinical HIV/AIDS care and treatment services, records keeping and reporting system, facility preparedness for HIV I AIDS care and treatment, laboratory and pharmacy services (Mapunjo & Urassa, 2007). Given that issues of adolescents' health in sub-Sahara Africa especially relating to HIV have only recently been brought to the lime light, many health facilities particularly HIV treatment centres may still be preparing their facilities to adequately receive adolescents with probably limited knowledge about adolescent care. Generally, adhering to ART improves treatment outcomes. Yet, few studies have investigated treatment outcomes in adolescents. For example, lost to follow up could mean the patient has stopped treatment which could lead to disease progression or drug resistance 6 University of Ghana http://ugspace.ug.edu.gh in some cases and worse still death (Nabukeera-Barungi el al., 2015). In addition, retention in ART is one of the main target of HI V treatment programmes; however, it has been sho\W that adolescents are experiencing extremely poor ART outcomes compared to adults; this is resulting in increased mortality, loss to follow-up, and lower rates of viral load suppression in adolescents compared to other age groups (Bygrave et ai., 2012). Earlier studies in Cameroon have been focused on adults and treatment outcomes among HIV positive adolescents have been rarely reported (Fokam, el al., 2017). There was therefore the need to conduct this study to assess adherence to anti-retroviral treatment among adolescents in Cameroon with emphasis on the determinants, challenges and outcomes of treatment adherence. 1.2 Research questions 1. What is the level of adherence among HIV positive adolescents on treatment? 2. What are the determinants of adherence among HIV positive adolescents? 3. What are the challenges adolescents face adhering to treatment? 4. What is the level of facility preparedness towards care of adolescents? 5. What are the treatment outcomes of adolescents living with HIV? 1.3 Objectives 1.3.1 General objective The general Objective of the study was to assess the determinants of adherence to Anti- Retroviral Therapy and treatment outcomes among adolescents living with HIV in Cameroon 7 University of Ghana http://ugspace.ug.edu.gh 1.3.2 Specific Objectives The specific objectives were to: 1. Detennine the level of adherence among HIV positive adolescents who are on treatment. 2. Assess the detenninants of adherence to ART among HIV positive adolescents who are on treatment. 3. Investigate the challenges of adherence and strategies to improve adherence. 4. Assess the level of facility preparedness towards care of adolescents with HIV. 5. Evaluate treatment outcomes of adolescents living with HIV. 1.4 Research Hypotheses This study was guided by the following hypotheses. 1. The level ofa dherence among HIV positive adolescents who are on treatment is low. 2. Adherence to ART among HIV positive adolescents who are on treatment is detennined by demographic and socio-cultural, health service factors. 3. There are significant challenges to adherence to ART among HIV positive adolescents on treatment. 4. The level offaciJity preparedness towards care of adolescents with HIV is low. 5. ARV Treatment outcomes of adolescents living with HIV are low. 1.5 Justification This study assessed adherence and its detenninants as well as treatment outcomes among adolescents living with HIV. Adherence to ART has been shown as one of the most significant barriers for improving health outcomes in adolescents living with HIV (Haberer & Mellins, 2009). Aside the therapeutic effects of ARVs, it also offers HIV prevention benefits, delays drug resistance, and reduces the risk ofHIV transmission to others. Factors 8 University of Ghana http://ugspace.ug.edu.gh affecting adherence among this age group were studied and recommendations have been made, which could be used to improve treatment outcomes. The study also determined adolescents' views on improving adherence. This provided information about their expectations, beliefs and suggestions as far as their care and issues of adherence to ARVs are concerned. This information could be used to guide policies related to enhancing healthcare provision to ALHIV for better outcomes. Treatment outcomes among HIV positive adolescents were also measured. The treatment outcomes for the study included: retention, viral load suppression, CD4 response and lost to follow-up. This information could help bridge the gap in relation to knowledge about treatment outcomes in adolescents as data is unavailable for adolescents in Cameroon. This could further be used to inform decision making pertaining to adolescent's care. In addition, the study assessed facility preparedness towards care of adolescents living with HIV. Health facilities providing HIV services to adolescents must be adequate in terms of the material and human resource capacity and also the conditions in which care is provided such as infrastructure, equipment and staff. These include optimal patient-provider interactions, diagnosis, treatment, follow up and prevention activities (Donabedian, 2002). The study assessed the availability of space, trained personnel, treatment guidelines and organization of activities for adolescents with HIV. This information could be used to enhance decision-making given the importance of maximizing treatment outcomes of HIV in this age group. Finally, the findings of the study have identified gaps for further research in this area. 9 University of Ghana http://ugspace.ug.edu.gh 1.6 Chapter summary and thesis outline This chapter presents an introduction of the study with a background on adherence both at the global and local level. The chapter also provides a statement of the problem and the need for this study in Cameroon. The general and specific objectives of the study are also presented in this chapter. The other sections of the thesis are organised as follows: Chapter two presents literature review of published works on adherence and its determinants among adolescents. adherence measurement and treatment outcomes. The chapter also explains the conceptual framework of the study. Chapter three describes the methods and procedures of data collection and analysis; chapter four presents the study's findings, while chapter five discusses the results. The final chapter concludes and makes relevant recommendations. 10 University of Ghana http://ugspace.ug.edu.gh CHAPTER TWO LITERATURE REVIEW 2.0 Introduction This chapter presents a review of published material on adherence to ARV treatment among adolescents. It first describes the concept of adolescence, the effect of HIV on adolescence, the concept of adherence and the determinants of adherence. The chapter also provides an understanding of the adherence situation globally, regionally and in the Cameroonian context. Likewise. literature on mortality among adolescents with HIV as well as facility readiness towards care of adolescents is also reviewed in this chapter. The last aspect of the review looks at adherence measurements in various studies across globally. 2.1 The concept of adolescence Adolescence, a transitional phase of growth between childhood and adulthood is defined in physical and cultural contexts. Whereas age defines the physical maturation, cultural perspectives of adolescence vary from one context to the other (UNICEF, 20 11). According to the World Health Organization (WHO) an adolescent is as any person between the ages 10 and 19. This age range is a subset to the WHO's definition of young people as individuals between ages 10 and 24(WHO, 2013a). Most cultures regard the cycle of physical changes resulting in reproductive maturity as adolescence. These societies define adolescence as the period between ages 12 and 20 (Sawyer, Azzopardi, Wickremarathne, & Patton, 2018). Adolescence experience is unique for each individual and is largely dependent on the individual's growing up with differences in physical development, emotional experiences, cognitive maturation as well as the environment (Cieslik & Pollock, 2017). There are varied views on the various stages of the adolescence. Whereas some 11 University of Ghana http://ugspace.ug.edu.gh authors suggest a two stage division(UNICEF. 2011), others suggest tbree(Blum, Mmari, & Moreau, 2017). However, the various suggestions are all within the age limit for the stage of adolescence. The stage of adolescence can be categorized into two phases; early adolescence and late adolescence (UNICEF, 2011) or into three; early, middle and late stages ofadolescence(Blum et al., 2017). Early Adolescence The period of early adolescence begins from age 10 to age 14. Physical development generally begins at this stage. Development is characterized by a growth spurt at the initial phase and then it is continued by the development of the sex organs and other secondary sexual features. It is early adolescence that girls and boys are more conscious of their gender than they were as children, and they begin making modifications to their lifestyles in order to adjust or meet up with the societal or perceived norms. In the process, the adolescent experiences either a burst of anxiety or pride at this stage of physical development (Curtis, 2015; Taghizadeh Moghaddam, Bahreini. Ajilian Abbasi, Fazli, & Saeidi, 2016). The internal changes in the individual, although not as visible as the physical, equally overwhelms the adolescents (Lule & Rosen, 2009). According to UNICEF, 2011, the adolescent at this stage is vulnerable to taking risk, succumbing to peer pressure and being perplexed about their own individual and sexual identity(UNICEF, 2011). Middle Adolescence The middle adolescence is the second stage of adolescents' development. This spans from age 14 to 16. Adolescents at this stage are cautious of their looks. In addition, risk taking among them increases with the adolescence being extremely vulnerable to peer influences. Many of the adolescents' behavior and patterns of thought that develop during this period may extend into their adult life(Sawyer et al., 2018). The adolescent at this stage show more 12 University of Ghana http://ugspace.ug.edu.gh signs of physical and psychological maturation. Hormonal changes most adolescents could cause feelings relating to sex, irritability, agitation. resentment and tension (Malin, Liauw, & Damon, 2017). Late Adolescence The age of 17 commences this phase of adolescents' development and ends at age 19. There are major physical advances at this stage with a lot of the physical features maturing. The adolescent's brain continues to develop, and they become analytical and reflective in thought. Vulnerability to peer opinions continues at this stage of development. However, it decreases as the adolescents gain increased understanding and boldness in their own identity and judgments (Curtis, 2015; Maliye & Garg, 2017) The concept of adolescent is dynamic and varies from one context to the other. In addition to the visible physical processes that the individual undergoes, other factors such as the psychological, social and cultural factors come to play in defining adolescence. The environment also plays a major role in the development process of the adolescent. Whereas an adolescent in a developed country will have access to their basic needs of life and intormation on their developmental needs, others in the less developed countries could have limited access (Taghizadeh Moghaddam et al., 2016). Lack of education, limited access to infonnation. culture and poverty predisposes adolescents, especially those in poor countries to risky behaviours. These behaviors include early marriages, trans-generational sex, and sex trading. In conclusion, programs targeting adolescents cannot be designed in isolation. The stage of the adolescents and the context all playa major role in programming for adolescents (Maliye & Garg, 2017). 13 University of Ghana http://ugspace.ug.edu.gh As of2018, Cameroon had a total population of25, 914, 285 people and over 7million of these were youth and adolescents age 1O-24years(BUCREP, 2019). The HIV epidemic has not spared adolescents in Cameroon as there are over 40,000 living adolescents with HIV in Cameroon(UNICEF, 2015). Statistics from the World Health Organisation showed that, a total of 1200 adolescents died from HIV/AIDS related causes(WHO, 2017). This study will hence focus on HIV among Cameroon adolescents, with emphasis on unveiling the determinants related to their adherence and treatment outcomes. 2.2 HIV and adolescence Adolescence (10-19 years) is a stage of physical growth and maturation that is characterised by sexual development and creation of intimate relationships (Naswa & Marfatia, 2010). mv positive children who live up to the adolescence, have challenges living up to their expectations as their normal lives are usually made complex by the presence of the HIV virus. (Vranda & Mothi, 2013). Hence. the adolescent mY/AIDS epidemic has its uniqueness and required to be managed cautiously and differently from the adults (ibid). This is so because adolescents who have the virus have to face the challenge of adhering to life-long medications and other adolescent issues especially those relating to their sexuality. HIV affects the lives of adolescents both socially, psychological, physically and health wise. Ont! characteristic that distinguishes HIV from other the other chronic illness is the stigma involved hence. adolescents and their families are faced with this stigma and the adolescent has to deal with it for a life time (Embree, 2005). In most cases, the adolescent and family live in a system of silence and shame which is linked with the disease (Vranda & Mothi, 2013). This stigma could be from home, schools, hospitals and sometimes from the media. Stigma has been shown to determine an adolescent's ability to live positively with HIV as it is associated with shame, social isolation and depression (WHO, 2013a). 14 University of Ghana http://ugspace.ug.edu.gh HIV positive adolescents are exposed to a number psychological factors over long periods oftime(WHO, 2013a). These could partly be attributed to status disclosure, thoughts about financial strains, adherence and other issues which can cause mental. A study by Gauhan and others in 2004 showed that HIV positive children and adolescents have a high burden of mental diseases (Gaughan et al., 2004). The mental issues are bound to happen as adolescents begin thinking of the future and how to live on. These thoughts could be worsened if they are not offered adequate psychosocial support and counselling. Health wise, adolescents with HIV are faced with the challenge of adhering to ARVs by taking medications on daily basis. They are also supposed to keep to hospital appointments which could sometimes affect their schooling and day to day activities. Furthermore, some of the ARV drugs could cause side effects which may be a reason for them to skip school in severe cases. Some studies have shown that HIV is one of the commonest cause of hospitalisations among adolescents. One of such is the prospective cohort study in Zimbabwe which showed that hospitalisations were higher among HIV positive adolescents (Ferrand et aI., 2010). Another study in Southern Africa had similar findings as adolescents were reported to contribute significantly to hospital admissions (Gray, 2010). Additionally, some HIV infected adolescents are supposed have to support and sick parent, take of their finances and that of siblings. This could be worse if the adolescent has lost one or both parents and does not have adequate parental support(Smith Fawzi et al., 2010). All these complicates the life of the adolescent especially coupled with the HIV condition they are already battling with. In summary, the adverse effects of HIV on the growth and maturation of adolescents could cause numerous difficulties for them as they sail through their teenage age (Vranda & Mothi, 2013). Hence, as HIV infected children become adolescents, they need adequate 15 University of Ghana http://ugspace.ug.edu.gh support in other to manage the complex issues of the disease, their sexuality and development(WHO, 2013a). Adolescents with HIV will need supportive advice which will inform their decisions and choices in life about their health, HIV disclosure to family and friends and their sexuality (Vranda & Mothi, 2013). This is important as this will prevent high-risk behaviours among the adolescents and promote safe healthy sexual behaviours (ibid). 2.3 The Concept of Adherence There are varied definitions of adherence. A number of authors consider adherence to mean an individual's ability to follow treatment as planned, take medications at prescribed times and frequencies, and follow restrictions regarding food and other medications (Taddeo, Egedy, & Frappier, 2008; Sabay, Reddy, & Dhayarkar, 2011b). From another perspective, it has been defined as the extent to which an individual's behaviour of taking medication, following a diet, adjusting habits and attending clinics coincides with medical or health advice (Touchette & Shapiro, 2008; Chakrabarti, 2014). Moreover, adherence also refers to the ability of the patient to act in accordance with the prescribed interval and required dosage of the treatment (Cramer et 01., 2008). Adherence has also been considered as the degree to which a person uses a medication following the required medical prescription, including timing, dosing, and consistency (Chaiyachati, et 01.,2014). From these definitions, the common theme across them is the fact that, the patient has to take medications as per the prescriber's advice. Regardless of the definition, the associated benefits of treatment adherence can only be obtained if the individual follows the treatment prescription meticulously (Osterberg & Blaschke, 2005). Generally, the concept of adherence is similar in both developed and developing countries. However, in some places, compliance might be used for adherence, but in places like the 16 University of Ghana http://ugspace.ug.edu.gh UK, the tenn concordance to treatment is preferred (Home et al., 2005). Compliance is the degree in which the individual's behaviour ties with recommendations of the prescriber. As for concordance, it is defined as a mutual relationship between the individual and the prescriber, where issues relating to treatment are discussed and an agreement is reached as to the treatment of choice which is acceptable to both the patient and the prescriber (Kane &, Robinson, 2010). Similar to concordance, adherence also means the act of involvement and active participation in the plan of care for a patient. The meaning of the concept of adherence is broader compared to compliance which is the extent to which an individual is able to go according to instructions which in the long run signifies commitment, understanding and agreement to his or her plan of care (Kane &, Robinson, 2010). These includes readiness to continue a peculiar program of care which details appointment for meetings, counseling and tests. An adherence of 95% or more is described as near perfect adherence. According to Bangsberg, the newer HIV regimens are more forgiving hence an adherence rate lower than 95% could still cause viral load suppression (Bangsberg & Deeks, 2002). However, this does not pennit patients to fall short of adhering properly to their medications. Hence efforts are on the rise to increase acceptor rates of ARVs among HIV populations from governments and other organizations. However, there is the need for more specific initiatives and patient-oriented strategies to ensure correct use and increased adherence to ARVs at all levels (Nsimba, 2010) Compliance, however, has been criticised and rarely used as it means sticking to medications without any considerations of the patient's social and personal issues (Lutfey &, Wishner, 1999). Persistence is also another related tenn and it is defined as the sustained adherence over time to the medication prescribed (Kane & Robinson, 20 I 0). Adherence has 17 University of Ghana http://ugspace.ug.edu.gh been generally used as it goes beyond compliance since the patient has to agree with the recommendations from the prescriber. With adherence, the patient is actively involved or is even seen as a partner as far as decisions regarding their care is concerned. Adherence is a complex and diverse issue that can change with time and with factors varying among patients and changing with time also (Kane & Robinson, 2010; Roux el ai., 2011). However, in cases of chronic illness, adherence could change over time and hence the term persistence may perhaps be used. In any case, regardless of which word is preferred or used, the impact of treatment can only be obtained if patients take their medications accordingly (Osterberg & Blaschke, 2005). From the literature, however, adherence is most widely used than any of the related terms. It is to this effect that the term is preferred and indeed used in the context of this study. 2.4 Adherence to ART The number of people living with HIV and receiving ART has risen by a third since 2013 and this is thanks to global efforts in improving access to ARV drugs (Heestermans, Browne, Aitken, Vervoort, & Klipstein-Grobusch, 2016). By 2015, there were 17million people receiving ARVs globally and there are expectations of further increases as per the UNAIDs target (ibid). Treatment and management of chronic diseases and conditions entails a system of medication which is usually based on long period of continuity, with failures resulting into sup-optimal medication outcomes, re-hospitalization, increased cost of care as well as more time lost. The World Health Organization has documented non-adherence to medication and treatment regimen for chronic diseases and conditions highly problematic with non- adherence rates varying from 15-39%, and 50% as an average (WHO, 2003). Various factors 18 University of Ghana http://ugspace.ug.edu.gh determine adherence to treatment among diverse populations. The factors range from social to economic factors, health system related and individual-related factors (Kalogianni, 2011). HIV has remained a chronic disease affecting many people across the globe especially in countries of Sub-Saharan Africa. However, there has been significant improvement in treatment especially with the use antiretroviral treatment (ART). The introduction and use of ART has transformed the HIV disease to a chronic illness in which patients remain on treatment for a life time (Chaiyachati et ai., 2014). Certainly, the introduction and use of ART since the 1990s has significantly increased the survival of HIV infected persons especially in Africa. Although ARVs do not cure the virus, they control viral levels and can substantially reduce the viral load so that in some cases it becomes undetectable in blood samples as long as the patient can adhere to treatment (Laing & Hodgkin, 2006). According to the World Health Organisation, ARTs do not only prolong life but can also reduce HIV transmission to others (WHO, 20 13b). However, it requires the patient to adhere critically to medications because an increase in adherence is usually accompanied by a reduction in the viral load. A study by Cohen showed that, poor adherence to medication is a predisposing factor for the development of drug-resistant HIV strains (Cohen et al., 20 11). This was further confirmed by N garina and others that revealed that, low levels of adherence were associated with high viral loads and replication of drug resistant viruses which may require more complicated treatment regimen as well as increased cost of care (Ngarina M. Popenoe R, 2013). Furthermore, adherence to ARVs prevents the e of AIDS, other opportunistic infections as well as emergence of drug-resistant strains of the virus. Hence improvements of adherence is a one of the key strategies to reduce and possibly end HlV/AIDS. 19 University of Ghana http://ugspace.ug.edu.gh In order to improve access to ARVs, the WHO launched the "3 by 5" initiative which was aimed at treating 3 million HIV positive persons by 2005 (WHO, 2004a). According to this initiative, WHO aimed at providing ART to 3 million people by 2005 in low and middle income countries however, only 43% of this target was achieved as only 1.3million people received ART by 2005 (Hardon e/ al., 2006). This initiative was closely followed at the end of 2005 by another target, which aimed at universal access to treatment by 2010 for all people with HIV (ibid). The commitment of universal access to treatment was done by the 08 countries and was aimed at having all persons living with HIV on treatment by 2010 (08,2005). The commitment towards universal access to treatment was, however, not achieved although some progress was made as more people were enrolled into treatment. Recently, the WHO declared the 90-90-90 target for HIV by 2020, with the aim to getting 90% of all people to be aware of their HIV status, 90% of all HIV -positive persons having access to treatment, and achieving 90% viral suppression for all on treatment(Levi et al., 2016). According to UNAIDS, some countries have made substantial progress towards achieving the 90-90-90 target. For example, Australia has achieved the first and second 90 target and is near achieving the third. Some African Countries like Botswana, Zambia, Zimbabwe and Algeria have achieved the second 90 while countries like Nigeria, Ethiopia and Mozambique are nearly achieving the second 90 (UNAIDS, 2017a). According to the progress made so far, Cameroon has not achieved and is not near achieving any of the 90- 90-90 targets. The use of ART has changed the HIV disease from being deadly into a chronically treatable condition for a greater proportion of people living with it; the worry with ART is how to maintain people on these medications given they have to take them for a life time (DHHS, 20 University of Ghana http://ugspace.ug.edu.gh 2016). Initially, this was partly because the drug regimens were complex, demanding and with multiple side effects and this caused a reduction in retention rates and adherence over time (Hansana el al., 2013). However, from 2016, there has been a lot of changes in regimens to friendlier and less toxic regimen, such as TenolamlEFV (TLE) and the recent shift to TenolamlDolutegavir (TLD) (Ibid}. Generally, adherence levels are lower in SSA compared to the developed world; it ranges from 60% to about 85% (Pefura-Yone, Soh, Kengne, Balkissou, & Kuaban, 2013; Letta, Demissie, Oljira. & Dessie, 2015). A study by Hawkins and others reported adherence levels in the UK to be 92% among adolescents(Hawkins el al., 2016). In Cameroon, adherence to ARV in adults was reported to be 73% after one month of ART initiation and this later dropped to 61 % 24 months later in 2011(Roux et al., 2011). These findings confirm the need for continuous assessment of adherence and its determinants as they change over time. Levels of adherence start declining in individual patients as they stay longer on treatment. Also, the need to maintain patients on treatment for a lifetime calls for the need for a long term perspective on adherence to ARVs. 2.5 Consequences of Poor Adherence Adherence to the ARV drugs is necessary to obtain the whole benefit of treatment (Chesney, Morin, & Sherr, 2000). A major concern with ART is the development of viral resistance, which is has been attributed to poor adherence. Antiretroviral therapy reduces morbidity and mortality; however, these are dependent on the patient's ability to sustain adherence over time (Tiyou, Belachew, Alemseged, & Biadgilign, 2010). Evidence has shown that missing above 5-10% of doses is associated with increased CD4 counts, high viral loads, disease progression and in death in extreme (Machtinger & Bangsberg, 2006). It also increases the risk of viral transmission to others. 21 University of Ghana http://ugspace.ug.edu.gh Moreover, poor adherence could cause a an increase in the replication rate of HI V with more susceptibility to mutations in the process, which has been associated with the development of new strains with reduced sensitivity to antiretroviral drugs (Walsh, Mandalia, & Gazzard, 2002; Chaiyachati et al., 2014). It is thus necessary to pay attention to adherence to treatment because non-adherence adversely affects treatment outcomes and could cause more undesirable effects. This should therefore be an important component and priority of public health efforts in improving and sustaining ART adherence. 2.6 Adolescents living with HIV Adolescents with mv can be classified into two groups: those that acquired the infection through mother-to-child-transmission also called vertical transmission (perinatally infected) and those that acquired horizontally, sexually or through blood transfusion (Denison, Koole, cl a/., 2015). An estimated 64% of all newly diagnosed HIV infections among adolescent in 2014 (140,000 out of 220,000) were reported in adolescents of Sub Sahara Africa and 71% of new adolescent infections in this region (98,000) were among girls (UNICEF, 2015). There are a substantial number of HIV positive adolescents live many parts of Africa who do not know their HIV status and are not opportune to counselling and testing services and hence some of them continue to be a source of new infections without their knowledge (Adejumo, Malee, Ryscavage, Hunter, & Taiwo, 2014). Although most of the new infections that are diagnosed in children and adolescents daily are mainly attributed to mother to child transmission, there is a small proportion of infections that are transmitted sexually (WHO, 2013a). Both have mUltiple, complex, overlapping, and different challenges to adherence (Sung-Hee, McDonald, Kim, Foster, & Fidler, 2015). From Figure 1, the incidence of global HIV infection among adolescents was very high around the year 2000 and started declining. 22 University of Ghana http://ugspace.ug.edu.gh 500000 450000 400000 350000 300000 250000 200000 Figure I: New HIV infections globally 2000-2016 among Adolescents (10-19 years) Source: (UNAIDS, 2019) The incidence was particularly high between 2000 and 2002 because children born to HIV + mothers from the late 80s had survived to adolescence. The significant drop from 2000 was probably because of the Prevention of Mother to Child Transmission (PMTCT) of HIV programmes which were introduced and scaled up and thus significantly reduced transmission to children. Even though enonnous efforts made by the global community championed by WHO and other partners to scale down HIV infection and to improve on HIV treatment which have all lead to substantial reductions in HIV morbidity and mortality, Africa especially South of the Sahara still lags behind in adequately responding to the public health problem. Figure 2 shows HIV prevalence by country in Africa among adolescents. Although Cameroon is not one of the highest hit countries, the number is still very high: between 20,000 and 49,999 adolescents were infected with HIV by 2014. In addition. over 50% of all the adolescents with HIV live in 20 countries, with South Africa taking the lead. These countries are known as the high burden countries and Cameroon is one of these as shown in Figure 3. 23 University of Ghana http://ugspace.ug.edu.gh Figure 2, Global distribution of number of adolescents aged 10-19 years living with HI V by country in 2014 Source: (UNICEF, 2015) TOTAL 2,000 Bralt! 31000 1,\ '...fe-·;lCf"a!IC~Jt U,,,,,,,;,1IIg< 36,000 1'11. Umted RepublIc nf Tanzama 110,000 Figure 3, Proportion of adolescents aged 10 - 19 living with HIV, by selected high-burden countries 2014 Source: (UNICEF, 2015) 24 University of Ghana http://ugspace.ug.edu.gh 2.7 Adherence to ARV among adolescents Generally, the goal of Anti-Retroviral therapy is to suppress the virus to the lowest level for a long time, preserve or restore the body's immune function, improve as well as prolong the life of the patient taking the treatment (Elaine Gross, 2004). According to the World Health Organization as cited in Nachega et aI., 2009, the number of adolescents on ART continues to be on the rise (Nachega et al., 2009). This reflects major improvements in antiretroviral therapy (ART) availability and access as well as a successful treatment ofperinatally infected children (ibid). It could also be due to newly acquired HIV infections through high-risk behaviour during early adolescence (Evans et al., 2013). In 2016. ART coverage among children below IS years in sub-Saharan Africa was only 43% compared with 54% in adults (15 years and older) (Kasedde, Kapogiannis, McClure, & Luo, 2014). As the number of adolescents on ART continue to increase, the challenge of obtaining and maintaining adherence over time for this age group has been difficult and pose a problem for survival and further disease spread (Hudelson & Cluver, 2015). According to the HPTN052 study, the paradigm shift in HIV prevention strategies to reduce HIV transmission and improve viral suppression must include risk groups like adolescents and adults living with HIV otherwise the global agenda will not be achieved(Cohen et aI., 20 II). Therefore, the subject adherence among adolescents is of utmost importance as they are also part of the global 90-90-90 UNAIDS target for HIV by 2020. Adolescents are at risk of suboptimal adherence and have challenges in suppressing viral replication, and this increases the chances of viral progression and the occurrence of opportunistic infection, transmission to sexual partners and viral resistance (Hudelson & Cluver, 2015). Moreover, fmdings from a study by Adjumo and others are of the view that 25 University of Ghana http://ugspace.ug.edu.gh horizontally-infected adolescents are more at risk of poor adherence compared to their perinatally infected peers (Adejumo el al., 2014). Sub-Sahara Africa has 85% of all the adolescents with HIV (Kasedde, Luo, McClure, & Chandan, 2013). About 1.3 million of the adolescents with HIV in Sub-Saharan Africa are in Eastern and Southern Africa, with an estimated 390,000 of them living in West and Central Africa (Idele et al., 2014). With this significant proportion of ALHIV, it is necessary to discuss their adherence. However, few studies have measured adherence among adolescents around Africa, although adherence has been reported to be lower than that of other age categories (ldele et al., 2014; Maskew et al., 2016). Adherence among adolescents in Africa has been reported by Kim et aI., 2014 to be 62.3%. This result was obtained from a meta-analysis. The results suggested that adolescents in Africa were adhering more compared to those in areas like North America where adherence is as low as 54% (Sung- Hee et ai., 2014). Despite this higher adherence among African adolescents, there is still a need to improve on it given that Africa has more of the ALHIV. By the end of 2015, an estimated 7,100 children and adolescents less than 15years were recruited to treatment, although the proportion was expected to increase due to the universal access to ART for children program that was initiated nationwide (Fokam et al., 2017). A study in Yaounde, Cameroon, reported adherence to be 36% in 2017 among adolescents (Fokam et ai., 2017). Despite the significant number of adolescents already enrolled into treatment, little research has been done on the determinants of adherence in Cameroonian adolescents. With this huge number and the expected increase in the prevalence of HIV, there is the need to ensure adolescents are retained in treatment so as to achieve optimum adherence and hence clinical success. 26 University of Ghana http://ugspace.ug.edu.gh 2.8 Treatment Outcomes Prior to ART and even in untreated cases today, HIV infection leads to gradual deterioration of the immune system (that is, AIDS), which could cause morbidity and even mortality (Enriquez and McKinsey, 2011). However, the use of antiretroviral (ARV) treatment has changed the disease to a life time infection which can be managed if the treatment is taken properly (Bor et al., 2017). Generally, adherence to ART improves treatment outcomes. Studies have shown for example that, majority of the patients adhering to treatment are retained in care (Babatunde et al., 2015). The treatment outcomes range from viral load suppression, retention in care, CD4 counts, mortality and morbidity. 2.8.1 Viral load suppression Several studies have shown that the goal of HIV treatment success is suppression of HIV viral load (Enriquez and McKinsey, 2011). This entails that HIV -infected patient should have full access to treatment and take daily for a lifetime (DHHS, 2016). The reduction of the HIV RNA to below 400copies/ml of blood is termed viral load suppression (Geretti e/ al., 2008). Two successive viral loads conducted with results above 1000copies/ml indicates that treatment has not been successful (WHO, 2016a). However, reduction in viral load does not necessarily imply the person is cured but indicates that the virus has been controlled. The major objective of antiretroviral therapy is to reduce replication of the virus to an acceptable level. This is because viral load suppression catalyses restoration of the immune system and substantially reduces the chances of disease spread (Chhim et al., 2018). Furthermore, a reduction in viral load is also essential for reducing morbidity and mortality(UNAIDS, 2017a). Consequently, the World Health Organization (WHO) in 2013 introduced viral load suppression monitoring as a gold standard to follow up the treatment success (WHO, 2013a). Given the importance attributed to viral load suppression, UNAIDS 27 University of Ghana http://ugspace.ug.edu.gh made viral load suppression as one of the targets to achieve by 2020 among HIV patients wherein, 90% of all HIV positive patients are expected to have suppressed their viral loads. The Centre for Disease Control(CDC) released a report in 2014 showing that only 57.9% of all HIV positive persons had suppressed viralloads(CDC, 2014). According to UNAIDS data for 2016, viral load suppression among HIV positive persons was 19%(UNAIDS, 2016a). However, a recent study in Cameroon reported a viral suppression of 72% among patients who had been on treatment between 12-24months and 67% among those who have been on treatment for at least 48months (Tchouwa et al., 2018). Although these results show an improvement from the report of UNAIDS in 2016, it still fall shorts of the global expectation of 90% for viral load suppression. Generally, viral load suppression for adolescents should be comparable to adults initiating similar regimens. However, some cohort studies have shown otherwise with suppression lower in adolescents compared to adults, with rates from 28% to 78% compared to 90% for adults on similar regimens (Agwu & Fairlie, 2013). Normally, with appropriate adherence to therapy, viral load suppression is expected to occur in 6 months of ART initiation. The use of viral load measurements is also important as it offers the opportunity to monitor progress towards the third 90 of the UNAIDS 90-90-90 target, with an ambitious target of having 90% of all the receiving antiretroviral therapy suppress their viral loads by 2020. In Cameroon adolescents have been reported a lower viral load surpression compared to adults. A longitudinal cohort study by Fokam and others in Yaounde reported a suppression of 52% among vertically infected adolescents (Fokam et al., 2017). This is lower than the suppression of reported in adults of 72% reported among adults in Cameroon(Tchouwa et al., 2018). The study by Fokam among adolescents is one of the few in Cameroon that has reported viral load surpression among adolescents and this was done in Yaounde (Centre 28 University of Ghana http://ugspace.ug.edu.gh Region). The present study is therefore adding to this but assessing this treatment outcome in another part of Cameroon-North West and South Regions. 2.8.2 Lost to follow up (L TFU) Lost to follow up (L TFU) is defined as patient missing clinic days and refill for more than 90 days since the last clinic visit and has not been registered as a transfer case or death (Chi et a/., 2011). Although there have been significant improvements in ARV treatment, there are still cases of treatment dropout along the treatment (Berheto, Haile, & Mohammed, 2014). Lost to follow up has been shown to accounts for almost 56% of all attrition (Babatunde et al., 2015). Studies carried out in some parts of Sub-Saharan Africa have shown that about SOOAl of the people who test HIV -positive are lost and 32% of the people considered eligible for ART are sometimes do not end of making themselves available for treatment (Wools-Kaloustian et al., 2006). Findings from a study by Bertho and others 2014 indicated that the mean retention for people on ARVs reduces with time, from an estimated 86% at 12 months to 72% by five years (Berheto et a/.. 2014). Some studies from Sub-Saharan African countries have estimated that about 20% to 40% of patients on ART are lost to follow-up (ibid). Loss to follow-up (LTFU) causes non-adherence which could lead to an increase in morbidity, hospitalizations and sometimes mortality (Taiwo, 2009). Some predictors of lost to follow up are; decreased CD4 counts, occurrence of opportunistic infections such as tuberculosis, unreliable services, drug side effects. younger age like the case of adolescents and advanced stage of disease (Wools-Kaloustian et al., 2006). The chances of attrition are always seen to increase as patients stay longer in treatment (Berheto et al., 2014). 29 University of Ghana http://ugspace.ug.edu.gh 2.8.3 Retention Retention in HIV care can be defined as the continuous engagement to a full package of care aimed at preventing, treating and supporting the patients immediately they are initiated into treatment (Babatunde et al., 2015). It also includes the patient's ability to stick to important aspects of the treatment, perform requested laboratory exams and follow-up clinic appointments as per the national standards or based on the advice of the practitioner (Patel, Hirschhorn, Fullem, Ojikutu, & Oser, 2010). Retention can be defined at 3months, 6months, 12months. 24months and even 36months. Globally, retention rates stand at 94% and 83% at 6 and 12 months respectively (Fox & Rosen, 2017). In Sub-Sahara Africa, retention rates have been reported to range from 50 to 70% at 2years (Babatunde et aI., 2015). For paediatric HIV patients in low and middle income countries, retention has been reported to be 88% at 12 months, 72% at 24months and 67% at 36 months (Fox & Rosen, 2015). Retention in care decreases HIV related deaths and morbidities, as well as the incidence of new infections and emergence of HI V resistant strains (WHO, 2012). Some factors that reduce retention include advanced illness, stigma, unregistered transfer outs, provision of inaccurate personal information by patients and financial issues (ibid). Retention in care can be improved by offering ART care immediately (Bor et af., 2017). 2.8.4 CD4 Counts CD4 counts measures the number of CD4 cells in the body. CD4 cells are a class of white blood cells known as T-cells. They are used to monitor immune response to infection. The normal CD4 count ranges from 500 to 1000 cells. When the CD4 count drops to below 200, it is considered as the advanced stage of the disease otherwise known as AIDS (Wood et al., 2003). Evidence has shown that ARVs improve CD4 cell counts, which in leads to decreases 30 University of Ghana http://ugspace.ug.edu.gh morbidity and mortality in HIV-infected persons (Wood et aJ.. 2003). Generally. as viral load increases. CD4 count decreases; therefore a low CD4 count is a consequence of virologic failure (Bisson el al., 2008). Hence, the higher the CD4 count, the better for the patient on treatment and this suggests that CD4 counts could be al so be a way of monitoring patient's response and compliance to treatment. 2.8.5 Mortality Mortality refers to deaths, and in this case, HIV related deaths. A review by kasedde and others in 2014 showed that, there \\as a decrease in HIV-related between 2005 and 2012 by 30% in other age groups. However. deaths among adolescents was rather seen to increase during this time by 50% (Figure 4) (Kasedde et al., 2014). T_oU.I adolescent AIDS-related deaths Total AIDS-related deaths -2!iOO-ooo- ---------- ~~=~~ 1_000 -300-00- -----_._------ 21. !iOOooo lIa ,0 ___0_ __ 2001 2lI02 2003 2004 2OD!> 2006 2007 20GII ..... 211\1 21111 2001 2002 2003 2004 2005 200II 2007 2008 2008 2010 2011 I igure 4: Total AIDS related deaths and deaths in adolescents Source: (Kasedde et al., 2014) HIV currently ranks as the second leading cause of adolescent deaths globally but ranks first among African adolescent girIs(UNAIDS. 2016c). In young adolescent boys, HIV is the third leading cause of death as of 2016(ibid). The observed rise in adolescents mortality from HIV w as attn' bu te d to lack of appropn.a te adolescent services to take care of the specific needs of the adolescents ranging from treatment to support services that could 31 University of Ghana http://ugspace.ug.edu.gh enable adolescents adhere to medication and hence improve their treatment outcomes(WHO. 2013a; Lall et al., 2015). Quality life among HIV positive adolescents The initiation and use of Anti-retroviral therapy (ART) in HIV management has seen a reduction in morbidity and mortality among people living with HIV. Furthermore, ARVS also increase life expectancy and quality oflife for most people living with HIV at the same time reducing the HIV transmission risk (Garcia de Olalla et al., 2002; Sethi, 2003; Samji, 2013; Bukenya, 2019). Furthermore, early treatment has increased the life expectancy of HIV patients to near normal. The primary goals of antiretroviral therapies (ARTs) are to control HIV replication, restore and preserve the immune system, decrease HIV transmission and infections, reduce complications caused by HIV and improve quality of life and survival (Garcia de Olalla et aI., 2002). The World Health Organization has defined Quality oflife as an individuals' view of their state in life within the context of the culture and value systems in which they live and relate to their goals, standards, expectations and worries(WHO, 1998). The patient's quality oflife also impacts the capacity to adhere to ARV treatments as well as treatment outcomes(Cooper, Clatworthy, Harding, & Whetham, 2017). Quality of life is measured using the WHO quality of life score tool which contains six domains namely; physical, psychological, level of independence, social relationships, environment and spirituality (WHO 1998) in (Dewan, GK, & Jiloha, 2009). Given the developmental stage of adolescents, measuring quality of life among them is imperative because it provides a more detailed monitoring of the physical, mental and social well-being of children and adolescents within their own stage (Lea, Gortmaker, McIntosh, Hughes, & Oieske, 2006). With increase access and availability of ARV drugs, the quality 32 University of Ghana http://ugspace.ug.edu.gh of life of HIV positive adolescents has increased (Aurpibul, Oberdorfer, Choeyprasert, & Louthrenoo, 2016). This study further affirms that the increased availability of ARVS has given a chance to children who were infected with HIV from mother to child to live to adolescents (Aurpibul et al., 2016). In Cameroon, a few studies have assed depression, and other psychological factors that can impact adherence (Gaynes et al., 2012; Fonsah et al., 2017). The quality of life of HIV patients which is also key to their adherence as well as treatment outcomes has not been studied in Cameroon. 2.9 Adolescents' perspectives on DIV and ART adherence Adolescents are gradually gaining prominence in the response to HIV as seen in the efforts of UNA IDS and other partners launching projects targeting adolescents (Armstrong, Rachel, Jane, Anke, & Liezel, 2013). Evidence also show that the number ofHIV related deaths are reducing in other age groups but, however increasing in adolescents(UNICEF, 2015). Given the situation, it is imperative to understand their perspective on HIV and ART adherence. According to the UNAIDS guidelines, it is necessary to partner with adolescents, understand their perspective and hence offer HIV care to them that is adequate and acceptable (UNAIDS,2016b). Perception is about an individual's beliefs that they can exert control over their own motivations, thought processes, emotional states and behaviour patterns (Wasti, Simkhada, Randall, Freeman, & Van Teijlingen, 2012). When these perceptions especially in the case of ARVs are negative, adherence is poor. Adolescents, like adults, vary in their opinion about adherence. While others deny the existence of the disease or perceived side effects, some believe that feeling better could mean the disease has been cured (Dahab et al., 2008). Adolescents also find health workers, peers and partners as significant others who can help 33 University of Ghana http://ugspace.ug.edu.gh improve on adherence and often feel that judgmental attitudes from health care providers negatively influences adherence (Armstrong et 01.,2013). In addition, inadequate social support for taking medications, break from medications, failing to understand the importance of drugs, beliefs of being able to stay healthy without HIV medications are some perceived factors reported to be related with poor medication adherence (MacDonell et 01.,2013). Health care providers also have their own views on ARV and they believe that long waiting time, work pressure on them, language barriers and insufficient time spent with adolescents are some barriers to adherence (Weiser et 01.,2003). The challenges of adherence are discussed below. However, a the believe in the value of treatment also helps adolescents to adhere to treatment (Dahab et 01., 2008). In addition, adolescents also believe that if other HIV positive adolescents who are adherent to treatment are used as models to share life experiences on how they live with the virus, it could help boast adherence among them (Armstrong et ai., 2013). 2.10 Challenges to Adherence The use of ARV medications has significantly scaled down morbidity and mortality from HIV globally(CDC, 2014). However, the ability of treatment to increase the quality of life depends on the extent of adherence. A number of studies have shown some of the factors that could hinder the patient's ability to adhere to medications as per prescription (Wools- Kaloustian et 01.,2006; Jayaweera et 01.,2009). As previously discussed, adolescents with HIV have been found to have lower retention in care compared with adults on a global scale and this can be attributed to a number of individual, social and health system related issues (Willis et a/., 2019). In spite ofthe global effort made to improve adherence in adolescents, ALHIV, their guardians or parents are still unable to access adolescent-specialised services which can enable them manage the disease (Denison, Banda, et 01., 2015). 34 University of Ghana http://ugspace.ug.edu.gh Among adolescents, the simple thought process makes it challenging for them to understand and accept the need to take lifelong medications especially when they have no symptoms and not sick (Elaine Gross, 2004). This is the case when the treatment is taken every day like in the case of ARVs. Adhering to ARV treatment comes with challenges which vary among adolescents. Enriquez & McKinsey, in their review, identifies a number of barriers or challenges as well as facilitators of ARV therapy adherence (Enriquez & McKinsey, 2011). These barriers to HIV treatment adherence as identified by the authors can be group under several major categories and include individual, socio-economic factors, health service factors and medication related issues. 2.10.1 Individual factors Adolescents who are HIV positive go to school, work, play or carryout routine domestic activities just like their counterparts who may be free of the virus. These activities may thus hinder adherence and as a result, many adolescents are discouraged from taking medications because they do not want others to learn about their HIV status especially due to the stigma attached to HIV (Murphy et al., 2003). Recently diagnosed adolescents have difficulties accepting the situation, and some could resort to drug use and alcoholism, which also impede adherence to ARV s (Shubber et al., 2016). For some adolescents, being out of home, fear of stigma, using of traditional medicines and denial of status, that is refusal of the HIV positive status are some of the individual barriers adolescents face while taking ARVs (Dahab et al., 2008). Likewise, psychosocial factors, such as despair, guilt and safe have been seen to hinder adherence (Lall et al., 2015). 2.10.2 Medication Factors Adolescents face medication related side effects like insomnia, hallucinations, lipodystrophy (redistribution of body fat), rashes or discoloration of the skin, that change 35 University of Ghana http://ugspace.ug.edu.gh their physical appearance and act as barriers to adherence (Merten et al., 2010; Sung-Hee et al., 2015). Pill burden. severity of HI V as a disease and low perceived need for medication are some challenges of medication adherence in young people (Buchanan et al., 2012). In addition, medication frequency, taste and treatment fatigue are also some factors that make adherence to ARV difficult (Sung-Hee et al., 2015). Feeling well after taking medication is also another reported barrier since there is the temptation to stop medication (Dahab et al., 2008). 2.10.3 Hcalth Service factors Health service factors are factors related to provision of care and availability of adolescent friendly services. These factors include long waiting time for drugs, laboratory tests and other clinic services, which take long and hence discourage adolescents from keeping to their appointments (Dahab et al., 2008). Long distance to clinic, poor quality of care, transportation costs and inconvenient clinic hours for adolescents are some of the barriers adolescents face as they take ARVs (Hudelson & Cluver, 2015). Also, poor communication and little or no trust in health care providers also impede adherence as there is no forum for discussion especially when adolescents encounter difficulties with their medications (Dahab el al., 2008). Impaired access to healthcare services together with smaller services and small staff numbers have been shown to also impede adherence (DagH-Hernandez, Lucchetta, de Nadai, Galdur6z, & de Carvalho Mastroianni, 2016) 2.1 0.4 Socio-economic Factors Infected adolescents face a number of life stressors which range from poverty, unstable family, movements or transfers to new environments. These factors which can also impede their access to ARVS and hence and adherence (Havens, Mellins, & Hunter, 2002). In the case of poverty, they might need to pay clinic fees, transport and other hospital expenses. 36 University of Ghana http://ugspace.ug.edu.gh Sometimes proper feeding and schooling becomes difficult in cases of poverty and this makes adherence quite challenging (Abanem & Bongfen, 2017). 2.11 Determinants of Adherence to Anti-Retroviral Therapy among adolescents The determinants of adherence are those factors that undermines/supports an individual's ability to adhere to treatment. The maximum benefits of ARV s which are desirable treatment outcomes can only be obtained when patients adhere to treatment(Lyimo et al., 2012). The task of adhering to medication is not easy and has been seen to be affected by a number of determinants. They are many and range from socio-demographic, socio-cultural and patient to health service factors as discussed below. 2.11.1 Socio-demographic Factors Socio-demographic factors can determine patient's adherence. Some of the demographic factors include age, sex, literacy level, place of residence, religion, distance to health facility living and with parent/guardian 2.11.1.1 Age The relationship between age and adherence is complex. While some studies show age to significantly influence adherence others show otherwise. One systematic review for example revealed a positive relationship between age and adherence: younger age was shown to be associated with good adherence (Hudelson & Cluver, 2015). Findings from South Africa in a qualitative study also reported younger age to significantly influence adherence while older age was a barrier (Dahab et al., 2008). However, a study carried out by Dagli-Hemandez et a1. (2016) found age not to have any significant relationship with adherence. In addition, findings from Uganda in a mixed method study showed age to have no significant association with adherence (Nabukeera-Barungi et al., 2015). A survey in Kenya also reported age group 15-24 to be associated with poor adherence (Mukui et al., 37 University of Ghana http://ugspace.ug.edu.gh 2016). Further, results from a mixed method study in Tanzania revealed that age had no relationship with adherence (Nyogea el al., 2015). Given the complexity of age and adherence as reported in previous studies. the present study will therefore asses the nature of the relationship in the Cameroon context. 2.11.1.2 Sex A review of literature showed the relationship between sex and adherence to be inconclusive just like in the case of age. According to Nyogea et al., 2015 in a mixed method study, sex does not have any significant relationship with adherence. Also, findings from (Mukui et aI., 2016) showed sex to have no association with adherence. A Ugandan study by Nabukeera et aI. (2015) as well as a study by Dagli-Hemandez et al. (2016) showed similar findings with sex having no relationship with adherence. However, being male was significantly related with adherence in a study among Ugandan adolescents as males reportedly had higher adherence compared to female (Wiens et al., 2012). However, the same male gender was significantly associated with poor adherence in a study in Botswana (Ndiaye el al., 2013). Given these differences in relationship between sex and adherence, this study will also evaluate this relationship. 2.11.1.3 Educational level Literacy level of adolescents has also been shown in literature to determine adherence; the nature of the relationship is however complex as the relationship is often bi-direction. A study by Hubrich and others in Brazil showed no significant association between educational level and adherence (Haubrich et al., I 999). Further studies by Nyogea et al. (2015) and Hudelson et al. (2015) showed similar findings with no significant relationship with adherence. However, studies by Dahab (2008), Zao (2009), Mukui and others (2016) showed that a higher level of education is significant predictor of good adherence (Dahab et aI., 2008; Zou et al., 2009; Mukui et al., 2016). Nevertheless, a study in Nigeria found 38 University of Ghana http://ugspace.ug.edu.gh higher level ofeducation to be significantly related with non-adherence (Uzochukwu el al., 2009). 2.11.1.4 Distance to Health Facility The other demographic variables like distance to health facility have also been shown to affect adherence in some studies. A study in rural Zambia showed that despite long distance to health facility, patients were still very adherent (Carlucci el al., 2008). However, another study in Zambia in 2012 showed long distance to health facility to be associated with non- adherence(Yuri el al., 2012). A study in Zimbabwe also revealed that patients who have to travel longer distances of over 10km from home to health facilities were having sub-optimal adherence compared to those who were closer to the health facilities (Gonah & Mukwirimba. 2016). Furthermore, results from a study in Nepal found that long distance to health facility was significantly associated with non-adherence (Wasti ef aI., 2012). 2.11.1.5 Religion Religion is another demographic variable that can affect adherence and its impact on adherence has been shown in a few studies. A study in Uganda showed that belonging to certain religions was associated higher adherence. According to the findings of this study, Christians of the Pentecostal denomination as well as Muslims had a higher adherence compared to the others (Kisenyi, Muliira, & Ayebare, 2013). Conversely, a study by Wambugu and others in Kenya showed that religious affiliations did not have any association with adherence to ARVs (Wambugu, Peter, Mbuthia, Joshua, & Ndwiga, 2018). 2.11.2 Socio-cultural factors The most common reported socio-cultural barriers to medication in both low and high Income countries include; use of traditional medicines, beliefs in spiritual healing, fear of disclosure, inadequate social support, interpersonal violence and alcohol use (Merten el al., 39 University of Ghana http://ugspace.ug.edu.gh 2010). Alcohol use especially during festive periods, stigma and lack of family have particularly been sho'wn to hinder adherence in HIV positive patients in Nepal in a mixed method study (Wasti et a/., 2012). 2.11.2.1 Use of traditional medicines Traditional medicines which in some cases are referred to as complementary and alternative medicine generally include herbs, spiritual beliefs, acupuncture, acupressure, chiropractic care, massage therapy, meditation, visualization, therapeutic touch and micronutrients such as vitamins, minerals and multivitamins (Heestermans et af., 2016). Some studies have shown that traditional and complementary medicines is widely used by HIV patients (Babb el al., 2007). Although in great use, the effect of these medicines on medication adherence to treatment has been similar across studies. For example, a study in South Africa reported that, the use of herbal remedies among HIV positive patients was causing their adherence to ARV to decrease over time (Peltzer et al., 2011). Furthermore, results of Peltzer's study in South Africa showed that the use of herbal medicines was associated with non-adherence. A study in Ethopia by Legesse also had similar findings as the use of traditional medicines had a significant association with adherence (Legesse & Shewamene, 2015). Additionally, Dahab showed that an individual's belief and preference for other traditional systems of medicines also negatively affect adherence as they sometimes prefer these traditional medicines to ARVs (Dahab et al., 2008). 2.11.2.2 Beliefs in Spiritual Healing Beliefs in spiritual healing is another socio-cultural determinant of adherence. Given the complexity surrounding spiritual issues, its relationship with adherence to ARV has not been given a lot of attention, however, few studies have reported on its effect on ARV adherence among people with HIV. A study by Thielman in Tanzania showed that beliefs in spiritual 40 University of Ghana http://ugspace.ug.edu.gh healing was linked with lower adherence(Thielman et al., 2014). However, findings from a study by Zou et al showed that adherence to ARV was not significantly associated with the belief that prayer could cure HIV or with other religious factors (Zou et aI., 2009). These results were similar to those of another in Zimbabwe where religious beliefs had no effect on adherence (Gonah & Mukwirimba, 2016). 2.11.3 Health Sen'ices and System Factors Health service factors that may predict adherence in adolescents include waiting time, clinic hours, doctor-patient relationship and service delivery. For the purpose of this study, the health system factors considered are waiting time and attitude of health service staff. While some studies report these factors to have negative impact on adherence, others say otherwise. Long waiting for instance was long waiting time showed no significant association with adherence in a study in Zimbabwe by Gonah and his team (Gonah & Mukwirimba, 2016). For the attitude of health service staff, findings from Mozambique indicate that poor attitude of staff could cause poor adherence (Marega, Pires, & Samuel, 2017). Whereas, a study by Kalichman et aI., 1999 showed that attitudes ofheaIthcare providers had no relationship with adherence (Kalichman, Ramachandran, & Catz, 1999).Similarly, poor staff competences and concerns about confidentiality are linked with non or poor adherence (Sanjobo, Frich, & Fretheim, 2008). 2.11.4 Patient factors Adherence to ARV can also be influenced by patient factors. These factors among others include side effects, internalized stigma, losing pills, being busy, other illnesses or comorbid conditions, waking up early and not understanding treatment regimen. 41 University of Ghana http://ugspace.ug.edu.gh 2.11.4.1 Medication related side effects Like most drugs, AR Vs also come with related side effects. Some of these side effects decline over time although in some cases might cause a change in medications taken (Hardon et 01., 2006). The World Health Organisation defines drug side effect as a "a response which is toxic and unintended and which could occur at doses normally used in humans for the prophylaxis, diagnosis, treatment of disease or for the modification of physiological function (WHO, 2013b). Some of the common experienced side effects are nausea, headache, vomiting, anaemia and gastrointestinal tolerance (Negesa, Demeke, & Mekonnin,2017). Medication related side effects could also be visible for example, body changes, excessive perspitation, skin darkening, loss of hair, skin swelling gaining weight and rashes on skin (Li et 01., 2017). These visible side effects can cause low self-esteem, stigmatisation and hence lead to poor adherence to medication(Abel & Painter, 2003). These authors further noted that, in cases where the side effects persist, the patient might even quit taking medications for some time or completely. ARV drugs can also cause neuropsychiatric adverse reactions, examples include delusions, intense body heat, anxiety, dizziness and nightmares (Castro, Gonzalez, & Perez, 2015). All these side effect affect patient's ability to take medications. Some studies have shown that adverse drug reactions have an effect on adherence; a study in Malawi by Mckinney showed that adverse drugs reactions affected adherence (McKinney, Modeste, Lee, Gleason, & Maynard-Tucker, 2014). Similar findings were also reported by a study in China where side effects with the mediating role self-efficacy was shown to affect adherence(McKinney et aI., 2014). The present study will hence asses the relationship between adherence to ARVs and medication related side effects in the study area. Some of the HIV medications and their possible related side effects are as follows; 42 University of Ghana http://ugspace.ug.edu.gh Nucleotide Reverse transcriptase Inhibitors (NRTIs): These drugs function to stop reverse transcriptase, which is an enzyme that HIV virus requires to make copies of itself. Examples of NRTIs molecules are Abacavir, Didanosine, Emitricitabine, Lamivudine, Stavudine, Tenofovir and Zidovudine (Esser, Helbig, Hillen, Dissemond, & Grabbe, 2007). The related side effects of the drugs are as follows; - Abacavir, the relate side effect is hypersensitivity reaction. -Didanosine is noted to cause diarrhoea, abdominal discomfort, neuropathy, nausea, vomiting and pancreatitis. - Emitricitabine can cause rashes on skin and darkening, numbness and tickling sensations -As for Lamivudine, can cause the patient nausea, vomiting, stomach discomfort, diarrhoea, fatigue, body weakness, headaches and sleeplessness in some cases -Stavudine could cause the patient to develop peripheral neuropathy, headache, chills, fever, diarrhoea, nausea, losing of body fat around the face and sometimes on arm -Tenofovir can cause undesirable effects such as vomiting, appetite loss, stomach upset and mild nausea - Zidovudine related side effects are anaemia, nausea and vomiting (Esser et al., 2007) Non-Nucleotide Reverse transcriptase Inhibitors (NNRTIs): These are drug molecules that work by binding to and later altering reverse transcriptase which is an enzyme HIV needs to make copies of itself (Esser et al., 2007). These drugs also have associated side effects as follows - Efavirenz which causes vivid dreams, anxiety, rash, nausea and sometimes insomnia -Nevirapine which is known for kin rash, fever, headache, nausea and also diarrhoea - Rilpivirine that causes depression, difficulty sleeping, headache as well as rashes (Esser et al., 2007) 43 University of Ghana http://ugspace.ug.edu.gh Protease Inhibitors (PIs): Protease Inhibitors function by blocking protease, which is an enzyme used by the HIV virus to make copies of itself (Flexner, 1998). Examples of Pis are -Atazanavir: it causes side effects such as increased levels of bilirubin in blood, nausea, headache, skin rash, stomach upset, vomiting, diarrhoea and even changes in heart beat -Fosamprenavir which is associated with nausea. diarrhoea, vomiting, skin rash, numbness aroWld mouth and abdominal upset -Lopinavir can cause diarrhoea, fatigue, headache, nausea, weakness, rash and insomnia -Nelfinavir could cause diarrhoea, nausea, abdominal pain, weakness, rash, anaemia and joint pains in some cases -Ritonavir causes side effects such as nausea, vomiting, diarrhoea, changes in taste, headache. body weakness and skin rash -Tipranavir causes an increase in liver enzymes and cholesterol levels. It can also cause diarrhoea. rash, nausea, vomiting, stomach pain, fatigue and headache -Durunavir could cause some side which range from diarrhoea, nausea, headache and skin rash(Flexner. 1998). Fusion Inhibitors (FIs): These are the drug types that act by preventing the virus from binding to the cellular membrane of the host cell and hence blocking the entry of the virus (Trevor. 2006). The common fusion inhibitors is Enfuvirtide which can cause multiple side effects such as body itches, sleeplessness, depression, diarrhoea, mild nausea, body weakness, muscle pain, loss of appetite, weight loss and flu-like symptoms(ibid) Entry Inhibitors: These class of drugs inhibit the virus before it gets into the host cell. fheir mode of action is different from the fusion inhibitors (Qian, Morris-Natschke, & Lee, 2009) . The common example is Maraviroc which possesses the following possible side effects; cough, stomach pain, tiredness and dizziness especially when standing (Qian el af., 2009). 44 University of Ghana http://ugspace.ug.edu.gh Integrase inhibitors: Integrase inhibitors prevents the HIV virus from making copies of itself by blocking a key protein that allows the virus to insert its DNA into a healthy cell (Lataillade & Kozal, 2006). Examples of integrase inhibitors are; -Dolutegravir causes side effects such as headache and insomnia _ Elvitegravir could possibly cause diarrhoea, nausea and headache _ Raltegravir causes headache, nausea, dizziness, tiredness and insomnia (Lataillade & Kozal,2006). 2.11.4.2 Internalized stigma Internalised stigma in HIV care is a self- stigma in which an individual expresses negative thoughts or feelings about their HIV status(CDC, 20 IS). It is also known as imagined or feIt or perceived stigma (UNAIDS, 2006). Usually, the individual feels because they are ashamed, guilty or feel worthless about a particular health condition (Kalichrnan et aI., 2009). It is different from the normal stigma which is from comes from other sources. HIV/AIDS-related internalised stigmas can cause declines in physical and mental health (Rael & Hampanda, 2016). Internalised stigma is usually measured using six questions developed by kalichman. These are; -It is challenging to tell people about my HIV positive status - My HIV positive status makes me feel dirty -I feel guilty because I am HIV positive -My HIV positive status makes me ashamed - I sometimes feel worthless because I am HIV positive -I hide my HIV positive status from others. According to CDC 2018, a patient who answers yes to any of the above questions is considered to be experiencing internalised stigma. In the United states, SO% of HIV patients 45 University of Ghana http://ugspace.ug.edu.gh reported experiencing internalised stigma(CDC, 2018). This form of stigma was shown by Simbayi et af to affect adherence among HIV patients (Simbayi et al., 2007). Findings from Whitnney and others also showed similar results as internalised stigma was negatively associated to adherence (Rice et al., 2017). Another study revealed that, internalised stigma caused depression, anxiety and hopelessness which were associated with poor adherence to ARVs (R. Lee, Kochman, & Sikkema, 2002). The UNAIDS report on internalised stigma explains that this form of stigma Can affect family members and care givers who may also have internalised feelings of shame, fear or blame (UNAIDS, 2006) and this may consequently affect adherence especially in the case of adolescents who need care giver support. 2.11.4.3 Other illnesses or comorbid conditions In all age groups, people living with HIV have an increased chance of chronic complications and comorbidities, such as non-communicable diseases and mental, nervous and substance- use disorders(WHO, 2011). This WHO write-up further explains that, these conditions may be pre-existing, HIV -associated or due to ageing. A study by Gallant showed that 6.7% of patients on treatment had developed cardiovascular events while 31 % had hypertension(Gallant, Hsue, Shreay, & Meyer, 2017). These comorbidities affected ARV treatment choices and adherence to the medications. A study by Cantudo revealed that the concurrent use of ARV medications with other drugs to treat comorbid conditions affects adherence to ARVs(Cantudo-Cuenca, Jimenez-Galan, Almeida-Gonzalez, & Morillo- Verdugo, 2014). A major opportunistic infection associated with HIV is tuberculosis. It has been shown that, among people living with HIV, the probability of contacting TB is increased (Clumeck, Pozniak, Raffi, & Committee, 2008). Evidence shows that ARV treatment can have a 46 University of Ghana http://ugspace.ug.edu.gh significant toll on HIV and TB related morbidity and mortality in co-infected patients; as the simultaneous treatment of both ailments increases the pill burden (Dean et al 2002) in (Gebremariam, Bjune, & Frich, 2010). As a result of these complexities with medications and the added pill burden, HIV patients who are on TB treatment may experience lower adherence to treatment of both ailments. Given that adherence to ARV drugs, TB treatment and other opportunistic infections is key in achieving treatment success, it is necessary to assess how the presence of these comorbid conditions could affect adherence among adolescents. One of the patient factors that could affect adherence is losing the pills. The pills could be lost in travelling or as patients struggle to hide them in order to ensure their privacy. Loosing pills has not been widely studied as a determinant given that existing literature on this subject was rare. This study has therefore assed the effect of pills lost as a determinant of adherence. The other patient factors are being busy, waking up early and not understanding treatment regimen. These factors have also not been widely studied and their effect on medication adherence among adolescents were given a chance of assessment in this study. 2.11.5 Other factors Adherence is a complex issue and has a litany of factors that affect it. Having discussed factors relating to the patient, health system, socio-cultural and demographic determinants, there are still other factors that could also determine how an adolescent adheres to treatment. Some other factors that could influence adherence include pill burden, being aware of HIV status, no overall improvements in health, financial constraints, forgetting to take medications stigma and discrimination. These have been discussed below. 47 University of Ghana http://ugspace.ug.edu.gh 2.11.5.1 Stigma Stigma has been defined as a negative reaction to a situation which could be for example a physical deformity, a group of signs or symptoms as well as a behaviour in an individual that is believed to be undesirable or discrediting in a social setting (Goffman 1963 in (Martinez el 01.,2012). HIV related stigma is consist of all undesired attitudes, perceptions, negative beliefs attached to people who have HIV I AIDS as well as toward their families, friends and networks (Martinez el 01., 2012). A lot of the existing studies have noted that stigma remains a major fact of life for people living with HIV I AIDS in sub-Saharan Africa and referred it as "the central to the global AIDS challenge" as the HIV disease (Mann 1987) in (Fido. Aman, & Brihnu, 2016). People experiencing HIV stigma report a range of negative effects. such as losing their source of livelihood or job, segregation from their normal communities and being unable to fully participate as a productive member of the community (Visser, Kershaw, Makin, & Forsyth, 2008). This in some cases causes anger, the zeal to revenge and depression which can cause the individual not adhere to treatment(Fido et 01., 2016). Amongst HIV positive patients, those reporting stigma have a higher chance of non- adherence compared with those who are not faced with stigma (Rintamaki, Davis, Skripkauskas, Bennett, & Wolf, 2006). A similar study among youth also showed that the fear taking drugs in the presence of family, friends to avoid rejection also negatively affected adherence(Rao. Kekwaletswe, Hosek, Martinez, & Rodriguez, 2007). Furthermore, findings from a study by Martinez also had stigma predicting poor adherence and in this case among adolescents(Martinez et 01., 2012). In a related study in Nigeria, stigma was shown to influence adherence significantly, as patients experiencing stigma and discrimination reported lower adherence levels (Omosanya, Elegbede, Agboola, lsinkaye, & Omopariola, 2014) . In addition • sti gma, dlsc·nm·m·a·tlO n and disclosure were also shown in Uganda to 48 University of Ghana http://ugspace.ug.edu.gh correlate with suboptimal adherence (Nabukeera-Barungi et al., 2015). Kahema and his team in Northern Tanzania revealed that patients experiencing stigma had a higher odds (2.16) of non-adherence (Kahema, Mgabo, Emidi, Sigalla, & Kajeguka, 2018). However, other studies have reported otherwise showing that stigma does not affect adherence to medications(Mao, Li, Qiao, Zhou, & Zhao. 2017). 2.11.5.2 Forgetting to take medications Simply forgetting to take medications is a reported problem of many HIV patients as shown by a systematic review study(Mark, 2017) where it was the main factor affecting adherence as shown in majority of the studies. Additionally, forgetting to take medications also hinders adherence as was reported in a study in Ghana (Ankrah el al., 2016). A study among pregnant women also showed that forgetting to take medications was related with poor adherence (Zahedi-Spung, Young, Haddad. & Badell, 2018). Similarly, HIV patients on ARV treatment in Ghana indicated that, not being reminded or having a method of drug reminders was causing them to forget medication and this was shown to significantly affect adherence (Prah, Hayfron-Benjamin, Abdulai, Lasim, & Nartey, 2018). The authors of this study advocate the use of medication prompts among HIV positive patients in a bit to improve on adherence. 2.11.5.3 Financial constraints Globally, HIV drugs are given free of charge. However, there other associated cost of treatments as patients have to frequently visit the hospital for drug refills, perform routine laboratory exams and follow advice regarding their diets accordingly (Abanem & Bongfen, 2017). According to Wasti and others, associated treatment costs of HIV have a significant effect on adherence (Wasti et al., 2012). Another study in the Niger Delta in Nigeria 49 University of Ghana http://ugspace.ug.edu.gh reveaJed that the associated costs ofHIV treatment was associated with a reduced adherence (Nwauche, Erhabor, EjeJe, & Akani, 2006). 2.11.5.4 Pill Burden ARV drugs are taken on a daily basis and this is expected to be lifelong. Antiretroviral therapy (ARn is a combination treatment containing three or more antiretroviral molecules(Sutton, Ahuja, & Magagnoli, 2016). Multiple tablet regimens require two or more tablets per day and the higher pill burden is associated with lower adherence (Bangsberg, Ragland, Monk, & Deeks, 2010). This has been further shown in a number of studies where adherence is higher in patients with once daily and single tablet regimens (Fielden et 01.,2008; Juday, Gupta, Grimm, Wagner, & Kim, 2011). According to a meta- analysis of randomised control trials by Nachega and others, adherence was significantly associated with once daily regimen. However this was not shown to translate into better treatment outcomes (Nachega et 01.,2014). Similar findings were observed in a study by Carter 2014 as adherence was higher in patients taking one daily regimen compared to those on twice daily regime. There was however no difference treatment outcomes comparing one daily to h\;ce daily regimens(Carter, 2014). Furthermore, some findings suggest that, the simplification of treatment regimens could also help improve adherence to ARV treatment (Langebeek et 01.,2014). The other factors of treatment adherence; being away from home and improvements in overall health are also possible factors that can affect adherence. These factors have been assessed in this study to ascertain their role in mediating adherence among adolescents. The determinants of adherence discussed here appear to be interwoven as one adolescent can experience a multitude of these factors at a time. The determinants of adherence have 50 University of Ghana http://ugspace.ug.edu.gh been seen to vary from context to context and may even vary across age groups. Although the determinants of adherence to ARV have been given global attention as seen in the literature of published articles, there exist a paucity of information as to the determinants of adherence in the selected study area especially among adolescents. 2.12 Care of adolescents and health facility preparedness towards providing ART services 2.12.1 Care of Adolescents with HIV at the facility level The developmental stage of adolescents makes caring for them challenging and because the adolescents approach to the disease is different, their care is also supposed to be different form that offered to adults(Elaine Gross, 2004). The World Health Organisation (WHO, 2013a) has defined standards for quality healthcare for adolescents. The purpose of the national guidelines for the quality of health care delivery is to enable stake holders in health to improve the quality of care offered to adolescents so that the care is made accessible and available to these adolescents to improve on their general well-being (WHO, 2013a). The following steps are recommended guidelines from NACO 2013 for ALHIV(NACO, 2013); Step I: Establish rapport and relationship of trust with the adolescent. This can be done by: - Encourage peer involvement and help to identify treatment support buddies. - Encouraging disclosure. - Developing an individualised treatment plan for ARV that fits into the individual's lifestyle as well as identifying possible reminders. - Assessing individual's readiness for ART. This could be rated in terms of the individual's preparedness or ability to attend clinic regularly and not skipping appointments as well as taking other treatments such as cotrimoxazole and TB treatment S1 University of Ghana http://ugspace.ug.edu.gh _ In cases where the adolescents has challenges in adhering to regular doses adherence counselling should be reinforced. The possible challenges to adherence could be listed and strategies developed together with the adolescent to overcome these barriers _ Dietary requirements with ARV drugs should be adequately explained as some of the drugs are taken with or without food and some may need more water for intake - The possible medication related medication side-effects of the drugs have to be properly explained and understood by the patient before beginning the ART treatment - The use of other drugs such as herbal or traditional medications, could interact with ARV s. There is therefore the need for adequate counselling on the possible consequences of some of the traditional medicines on the health of the patient as they might have antagonistic properties with the ARVs they are taking - The patient should be educated on the need of regularly attending scheduled clinic visits adherence monitoring and other factors relating to treatment - The facility should have a proper follow-up system where patients can be called to be reminded of their hospital visit. In cases where a patient failed to meet up with an appointment, they should be called or visited at home Step 2: Counselling - which is should be in one or more individual sessions -The patient should be helped to explore their feelings. The patients have a varied number of social issues ranging from family, to relationships, job which can hinder adequate adherence. These should be discussed, and possible solutions suggested on the way forward -Issues relating to privacy should also be discussed. Some of the patients lack privacy and may not even have a proper and safe place to keep medications at home. Given that the fear of others knowing status is a possible reason for poor adherence, challenges relating to privacy should be identified and recommendations made to enable the patient to manage the situation. 52 University of Ghana http://ugspace.ug.edu.gh -The patient should have a significant other whom he/she can confide in as they may need encouragement and support from these when need -The health care provider should also asses the fmancial status of the patient as lack or inadequate finances may cause some patients to skip hospital appointments. If possible, the patient could be assisted to develop secondary support systems for themselves Step 3: Solving practical problems and creating a treatment plan Some of the common questions that could be asked include; -Where will the medication be kept at home? -At what time will the medication be taken? -What will make the remember to take medication or who will be there to remind himlher to take medications in case it is forgotten -What will happen in situations where the normal routine is interrupted? This could happen for example during travel. All these issues must be carefully addressed in a one on one counselling session with adolescent and guardian. In some cases, these concerns may not be sorted in a single session and will hence require multiple counselling sessions till the adolescent is comfortable with the desired treatment plan. Generally, studies have shown that adolescents generally avoid health services if they are not adapted to be adolescent friendly (Atuyambe, Mirembe, Annika, Kirurnira, & Faxelid, 2009). Adolescent friendly health services (AFHS) according to the WHO standards should be characterized as follows: Equitable: for all adolescents without any exceptions and they are expected to have access to the health services that are essential for them Accessible: Adolescents are able to have the services that are provided for them. Acceptable: The health services are offered in ways that meet the desires of adolescents. 53 University of Ghana http://ugspace.ug.edu.gh Appropriate: The proper health services that adolescents need are provided. Effective: The right health services are provided properly, and have a positive impact on the health of adolescents (WHO, 2015). Apart from having adolescent friendly health services, health care system are often lacking in the equipment needed to provide appropriate and effective care that meets the needs of these adolescents especially those with HIV(WHO, 2015). In many countries of Africa in particular, there is inadequate training and experience for health workers who care for adolescents as some of them become judgemental especially in issues relating to sex and this could hinder rapport with the adolescent and even cause them not to attend the facility subsequently (WHO, 20 13a). There is therefore a need to empower health workers and provide them with the necessary tools to care for ALHIV to improve their treatment outcomes. According to the National Guidelines on the Management of HIV in Cameroon (2015), disclosure can begin at age 10 years but if the adolescent encounters difficulties in adapting, it is better to wait until it is more comfortable to do so. The guideline gives recommendations for starting ART in adolescents according to the WHO 2016 guidelines (Tablel). 54 University of Ghana http://ugspace.ug.edu.gh Table I Recommendations for starting ARVs in adolescents and Adults in Cameroon 151 Line Alternatives -Tenolam Efavirenz -Duovir Nevirapine (TDF 13TCIEFV) (AZT/3TCINVP) -Duovir Efavirenz (AZT/3TCIEFV) -Tenolam Nevirapine (TDF/3TCINVP) 2nd Line Atazanavir-ritonavir (AZT/3TCIA T V Ir) 3rd Line Darunavir!DolutegravirlEtravine (2INT !DR V! DTGIETV) 2INT/DRVI RALIETV Source: National Guidelines for the Prevention and Management of HIV in Cameroon 2016 2.12.2 Health facility preparedness in Providing ART services to adolescents with HIV Globally, health care systems are still making progress towards having adolescent friendly health services to provide quality care for adolescents. Most of the HIV services provided are insufficient and do not meet the needs of adolescents (WHO & UNAIDS, 2015). In Cameroon there is a National Treatment Guideline for ART, which was first published in 2001, simplified in 2003 and later updated in 2006 and 2010. It was updated in 2015 to include the WHOs' 2013 recommendations and include a section on management of adolescents. The present guideline, which was updated in 2017, includes the WHO 2016 recommendation, test and treat strategy for all or treat all, and is recommended for use in all health facilities in Cameroon providing HIV treatment and care. According to the WHO guidelines for HIV services, adolescent friendly comers in health facilities should be secured, private and a away from sources of stigma so that adolescents and health care providers can have proper interactions that allow them offer health that is 55 University of Ghana http://ugspace.ug.edu.gh acceptable, effective and desirable for the adolescent (Aditi, Teltschik, & Davies, 2015). From these guidelines therefore, health facilities providing ART to adolescents are expected to have a separate adolescent comer and a written and regularly reviewed adherence strategy for adolescents (WHO, 2007). Facility preparedness towards care of adolescents on ARV can be accessed using the John Snow Inc (lSI) (2003) tool, which is the standard tool at the moment. The JSI tool looks at \arious aspects of care such as leadership, management of ARV drugs, programme protocols, experience and staffing and laboratory capacity. For leadership, the health facility should have a leader with vision and some experience in health care management. It also looks at the model of care which has been identified for use in the facility. In the case of management of ARV drugs, the facility ought to have staff with experience or training on ART, comprehensive services, physical space for drugs and for consultations with confidentiality and community involvement. For ART protocols, the health facility should own and use the National treatment protocol, a management information system and a system for monitoring and evaluation. For experience and staffmg, the health facility should have experience staff and should also have a plan for training and retention of staff. Finally, lor laboratory capacity, the facility should provide access for minimum laboratory test as per the WHO or national protocol guidelines. The laboratory should also maintain quality standards with a system for quality assessment. In Cameroon, there are treatment guidelines for HIV treatment which are inclusive of adolescents. Some health workers have also received training for care of adolescents to improve care but there is sometimes lack of continuity of care especially when the trained focal person is transferred (Ako-Egbe, 2018). Adolescents seeking HIV care deserve standard care which appeals to them and gives them more reason to always return to the S6 University of Ghana http://ugspace.ug.edu.gh health facilities. This is the case because adolescents are more likely to be adherent and present with better treatment outcomes if they returned in care through provision of quality services (Babatunde et al., 2015). There has been very little literature assessing the level of facility preparedness towards care of adolescents in Cameroon. Given the peculiar importance of standard of care as it may affect adherence to ARV s in adolescents, this study has examine the level of facility readiness to receive HIV positive adolescents. 2.13 Strategies to improve adherence to ART among adolescents Studies from both high and low income countries show that health services delivery for adolescents has gaps, is inconsistent and with varying quality standards (WHO & UNAIDS, 2015). It is therefore the role of health care providers to make more efforts in providing appropriate and adequate care to adolescents that helps them to overcome some of the challenges and barriers they face as they the take medications. The providers should also encourage and enable adolescents to make a commitment to treatment 0 as to improve treatment outcomes. Despite the modest progress made in HIV treatment, there is certainly the need to scale up adherence by identifying and mitigation barriers to adherence. Even though there are mUltiple strategies to enhance adherence depending on the setting, these authors offer varied suggestions that health care providers could consider. These approaches include: The patient should always be as sed of readiness to begin treatment before treatment I started and should be closely monitored. In case of treatment failure a possible substitute could be made • The health care provider together with the patient should identify the possible barriers to medication adherence and hence support the patient to identify possible solutions to the problems identified. The patient could also be helped to have social support network or system 57 University of Ghana http://ugspace.ug.edu.gh • Drugs should always be provided as per the treatment guidelines and where it permits, once daily regimens should be given preference over the others • Social factors such as drug abuse and alcohol should be discussed as well as the consequences on the health of the patient • Patients should be monitored for depression and other mental illnesses and offered adequate support as required. From another perspective, a recent study carried out in Rural Zimbabwe assessed the effectiveness of community adolescent treatment supporters (CATS) in improving linkage to care, retention rates, adherence to ART and mental well-being. A randomised trial among adolescents 10 to 15 years old living with HIV was conducted (Willis et al., 20 I 9). Based on a randomised trial, the study reported a significant increase in the factors of adherence such as confidence, self-esteem, self-worth and quality of life in the intervening group showing 3.9 times adherence higher than in the control arm (Ibid). It was revealed in this study that participants receiving the intervention showed a substantial improvement in adherence to ARV from 44.2% at baseline to 71.8% at the end of the study period According to these authors, the observed difference in adherence was a result of the use of the treatment supports in the community. Furthermore, the involvement of CATS with the health care providers offered adolescents the opportunity of expressing their worries and even make proportions of solutions to some of these problems. The community treatment supporters are well trained to support adolescents on ARVs. In this respect, the study recommends that community interventions that are managed by other adolescents should be used as means to improve on adherence among them. This should, however, be done after a similar study is carried out in other areas to ascertain these contributions of CATS. 58 University of Ghana http://ugspace.ug.edu.gh Furthermore, the initiation and use of adolescent friendly health services has improved acceptability and retention rates for adolescents especially those living v"ith HIV (WHO 2015). According to Asire and others in 2017, the use of adolescent friendly comers in health facilities that offer services at acceptable hours making provision for other health delivery settings such as schools and social centres, and mobile services that insure confidentiality can adequately improve their adherence ability (Asire. 2017). Similarly. attractions such as accommodating and friendly health workers, entertainments such as Television screens, motivations like snacks and transport reimbursement also impact adherence positively (ibid). Furthermore. the use incentives has also been shown as a means of improving adherence. A randomized control trial done in California by Sorenso and others revealed that the use of incentives to motivate HIV positive patients improved adherence. In this study, the participants were randomly assigned to two groups, control and intervention. The control group received health education on adherence and vouchers each time they took medications while the control received only health education. After 12 weeks, adherence was compared between the two groups and the intervention group had 78% compared to 56% in the control group (Sorensen et 01.,2007). Another strategy that has been tried to improve adherence is the use of psycho-education. One of such interventions was carried out by Tudra and to assess the effect of Psycho- education on medication adherence. The intervention arm received counselling relating to dealing with psychological issues while the control group received the normal routine counselling from health care providers. After 48 weeks, adherence was measured between the two groups and the intervention group reported an adherence of 94% compared to 69% in the control group (Tuldra et al., 2000). 59 University of Ghana http://ugspace.ug.edu.gh Additionally, the use of SMS (short message services) has also been shown as a means of improving adherence to ARVs and even other medications like tuberculosis treatment (Bediang, Stoll, Elia, Abena, & Geissbuhler, 2018; Sherman et al., 2018). One of such interventions is the randomised control trial by Bediang in Cameroon that used SMS as an intervention to assess its impact on adherence. The patients in the intervention arm received daily reminders to take medications while those on the control arm did not receive any. The results of this randomized controlled trial indicated an improved treatment adherence among patients who received reminder messages during their treatment for tuberculosis (TB) than those who did not(Bediang et ai., 2018). Additionally, in a qualitative study among patients receiving treatment for HIV in the United State of America, those who received daily reminder messages adhered more to treatment than those who did not(Sherman et al., 2018). Another randomized control trial by Pop-Eleches and others in Kenya also suggested SMS as an important tool for improving adherence in resource limited settings in Africa(Pop- Eleches el al., 2011). Moreover. a systematic review by Amankwa et ai., 2018, revealed that, scheduled messages to patients on ARV treatment made them adhere better than those who received no reminder messages (Amankwaa, Boateng, Quansah, Akuoko, & Evans, 2018). However, the use of SMS in adherence has not had consistent findings. A study by Mbuagbaw in Cameroon 2011 had contradictory findings. In this study adherence to ARV was compared between two groups- one group receiving weekly SMS reminders to take medications and the other group did not receive any reminders. Adherence was compared between the two groups at 6months and there was no difference in adherence (Mbuagbaw et al., 2011). 60 University of Ghana http://ugspace.ug.edu.gh Despite the existence of the above factors in mitigating the barriers to ART adherence, Scanlon and Vreeman (2013) in their study on "Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings" however, explains that individuals living with HIV continue to face challenges as they adhere to treatment. This is justified by the fact that there are still few evidence based interventions that can inform healthcare professionals and stakeholders who are at the forefront of adolescent care. (Vreeman, Gramelspacher, Gisore, Scanlon, & Nyandiko, 2013) The limited strategies to mitigate barriers to adherence is more common among vulnerable groups including women, children and adolescence and other high risk popUlations. Given that the strategies to improve on adherence vary within contexts, there is the need for the current study explore ways, among others, through which adherence can be scaled-up especially among adolescence that constitute a vulnerable group of persons especially in a developing country like Cameroon. Social support services for adolescents with HIV HIV support services are the are non-clinical services and the treatment of co-morbid conditions that are used together with ARVs to improve quality of life and reduce HIV and AIDS deaths (UNAIDS, 2016d). According to this report by UNAIDS, treatment support is necessary for the following reasons; support adherence to treatment as a means of improving viral load suppression and other treatment outcomes, for improved well-being and preventing further diseases spread; to also prevent the occurrence of other illnesses and properly manage them if they occur and coping the difficulties of living with the virus. Social support in HlV care is also defined as the assistance people receive, or perceive to have received from their social links (Matsumoto et al., 2017). The types of social support vary and range from emotional support which could be offered in terms of empathy, 61 University of Ghana http://ugspace.ug.edu.gh informational support which could be given through suggestions and advice and other physical support in terms of fmancial assistance and sometimes food or other materials (Cohen 1994) in (Matsumoto et al., 2017). According to these authors, social support could come from, family members, friends, neighbours and colleagues. Evidence from some studies have shown that social support systems improve AR V treatment outcomes among HIV positive persons on ARVs (Umberson & Karas Montez, 2010; Maman, van Rooyen, & Groves, 2014; Rouhani et al., 2017) According to the International AIDS Society (lAS), adolescent peer support models have demonstrated outcomes of improving retention, virological suppression and resulting in good psychosocial well- being (lAS, 2016). FurthernlOre, a study among HIV infected adolescents in Kenya showed that the use of a support group improves on the treatment outcomes(Levy et al., 2016). In Cameroon, a few studies have been done to assess the role of social support services in HIV care. One of such is a study in the Muyuka district that showed that community participation improved retention rates of HIV positive persons (Constance, Ngouakam, Thomas, & Nsagha, 2019). Another study in Cameroon also revealed that the decentralisation of HIV care to involve social support networks could improve quality care and adherence to ARV treatment(Boyer et aI., 2011). The role of the Care giver in adolescent care As indicated in the background of this thesis, there have been significant advances in the treatment ofHIV the world over, thus transforming the disease into a life time infection that can be managed. Most of these advances are attributed to the improvements in anti-retroviral treatments. One of the increasingly recognized contribution to enhanced adherence to HIV treatment is related to the quality of caregiving. This is particularly important especially with HIV infected children and young adolescence whose adherence to ART can be 62 University of Ghana http://ugspace.ug.edu.gh significantly determined by the caregivers' beliefs in necessity of treatment (Abongomera et al., 2017). Despite the potentials of caregivers to enhance HIV patients' adherence to medication, Mokwele and Strydom indicate that experiences of and barriers encountered by volunteers and community workers involved in HIV care to ensure that patients adhere to treatment has not been adequately documented. (ARn (Mokwele & Strydom. 2019). Nevertheless, some authors have equally underscored the importance of caregiving in HIV adherence in general and children, adolescence and youth in particular (Gichane et al., 2018) In an earlier study, Beals et al. examine the role played by women in promoting adherence to HIV medication among HIV -infected person in general and husbands and older sons in particular (Beals, Wight, Aneshensel, Murphy, & Miller-Martinez, 2006). In this study, caregivers are understood to be important in the patients' treatment adherence as they constantly remind them to take medications and to attend clinics as well. Other roles observed to have been played by caregivers in this study are; indicating when the patient has difficulties with medications such as side effects, treatment failure and other issues relating to the patient's ability to adhere to medications. In some other context where HIV stigma is still rife as in some parts of sub-Saharan Africa, caregivers are largely involved in dealing with stigma in order to improve adherence of family members especially young people. McHenry et al., in a study in Kenya among care givers of children and adolescents with HN gives the challenges they face especially relating to HIV stigma (McHenry et al., 2017). The study reports the negative and wrong perceptions about HIV held by community members about HIV transmission and prevention. This often gave rise to stigma which causes reduced or loss of social networks, economic support and could even give a chance to depression, mental illness or internalised 63 University of Ghana http://ugspace.ug.edu.gh stigma. According to the findings of the study, stigma was the main reason for non- disclosure of status, poor adherence depression and other psychological problems. In or order to establish the importance of enhancing effective caregiving, some authors have sho\\;n that social support is an vital aspect that could be used to improve on the physical and psychological health of caregivers and children affected by HIV I AIDS, especially in areas of the world where the disease is endemic such as in the developing world (Casale & Wild, 20(3). In a critical review aimed to empirically determine the evidence of the effects and processes linking support to caregiver health among HIV/AIDS-affected Care-Child dyads, these authors (Ibid) show the importance of social support for health among this population. However, the lack of evidence on the effects of social support on caregiving and patients in developing world makes it challenging to generalisations based on this study. As indicated by these authors, there is equally a need for further research on the psychosocial factors explaining the observed results. Gichane. el al. (2017) also note that youth living with HIV in sub-Saharan Africa are confronted with numerous adherence challenges. As many of these youths acquired the virus vertically, many of them are now orphans, making home-based care giving a daunting challenge as well. In their qualitative study of HIV infected orphans aged between 13 and 24 in Tanzania, the authors noted significant variations between paternal orphans cared for by their biological mothers on the one hand and maternal orphans cared for by their grandmothers on the other hand. Key adherence supports for these groups of orphans were centred on assisting the infected orphans in taking medication and attending clinic. However, double orphans in this study did not report support to adherence, indicating the lack of home care giving (Gichane et al., 2018). The understanding of this kind offamily context of orphans living with HIV is thus imperative in efforts to improve ART adherence. 64 University of Ghana http://ugspace.ug.edu.gh In a phenomenological study on the challenges and views of community caregivers with regard to antiretroviral treatment, Mokwele and Trydom emphasize that as a contribution to dealing with the effects of HIV and AIDS which have had a devastating effect on some communities in South Africa and recommended an improvement in the social support structures for patients who are on ARV (Mokwele & Strydom, 2017). This can be done by exploring the challenges experienced by community caregivers in order to benefit from their views (from their everyday life and experiences) and hence design community-based interventions aimed at improving adherence of patients to ART. This study explored and described the perspectives of three established community caregivers' organisations in Potchefstroom, South Africa, namely, Bambanani Youth Project, Baptist Children's centre and Hospice Emanuel Loving Angels. Most of the care to HIV and AIDS patients are done by these community health givers who were the key participants in the study. Much of caregiving to HIV infected persons often done by relatives and this is detennined by a range of factors such as care givers' income, gender, and age among other factors. Generally, those without steady occupations have been observed to be the principal caregivers to HIV infected persons. In a cross-sectional study on adherence to antiretroviral therapy among Brazilian HIV-infected children and their caregivers in Salvador, Ricci and his team indicated that caregivers were largely women who did not have a fixed salary, had formal education of less than four years, and were mostly relatives of the children between I to 12 years considered in the study (Ricci, Netto, Luz, Rodamilans, & Brites, 2016). These socio-demographic and economic characteristics of caregivers were observed to be significantly associated to 4-day children's adherence ~ 95% (p < 0.05). The role of caregivers is particularly fundamental to children and younger adolescence given that successful treatment ofHIV-positive children also needs an adherence level of at least 95% as is the case in adults. In the circumstances therefore, caregivers are often expected to 65 University of Ghana http://ugspace.ug.edu.gh pharmacy refill on behalf of the children, taking them to clinic as well as improving on nutrition. A similar study among caregivers ofHIV children and adolescents in Ethiopia reported that the main characteristic of the caregivers which had an effect on patients' adherence were their marital status and age (Eticha & Berhane, 2014). According to the testimonies and experiences of caregivers in this study, children whose caregivers were unmarried and married had a higher chance of adhering to their ART treatment more than those whose caregivers were divorced/separated. In like manner, children whose caregivers' were between age 25 and 44years also showed a higher adherence compared to the others. The care givers reported medication related side effects, pill burden, difficulty in swallowing the pill and depression as some the difficulties that could cause the children to miss medications. Tht: importance of caregiving to HIV treatment adherence is further justified by the fact that caregivers (given that they are adults) are the ones who can best present the physiological, social and economic determinants of HI V treatment adherence by children and adolescence. In their study on the "Factors related to antiretroviral therapy adherence in children and adolescents with HIVIAIDS in Cuba,"{Castro et al., 2015) explained the challenges faced by caregivers which could potentially undermine adherence if not addressed. As reported by caregivers in this study, poor adherence was attributed to social and psychological factors including the fact that the caregivers were overburdened especially if they were also sick, insufficient family support and in some cases untreated mental issues. The care givers in some situations even allow the children to their own medications even when they are not matured enough to take over the treatment responsibilities. The study hence shows the vital role of the caregiver and family support for treatment success in children and adolescents living with HIV/AIDS. 66 University of Ghana http://ugspace.ug.edu.gh Transitioning adolescents to adult mv care Health care transitioning in HIV care is defined as the purposeful movement of an adolescent from child-centred to adult centred-care(Tanner e/ al., 2016). The treatment outcomes of adolescents in adult care are largely dependent on how well they are prepared for transitioning to adult services. The adolescents are supposed to be empowered and supported to acquire individual self-management skills in order to adapt to the change (Yi et al., 2017). Some studies have revealed that, moving to adult care is a critical determinant of adherence to ARVs and treatment outcomes(S. Lee & Hazra, 2015). Evidence also has it that, transitioning to adult HIV care is associated poorer treatment outcomes such as loss to follow up, high viral loads and reduced immune recovery (Judd, Sohn, & Collins, 2016). Therefore, the transition process among adolescents should be informed by the contextual issues facing the adolescents while focusing on the social support system that will enable the adolescent transition successfully (Yi et al., 2017). According to the World Health Organization, moving an adolescent to adult care should be done when the done when the individual is aware of the status, has basic knowledge on this health care, understands the disease and the regimen and has acquired skills to manage their own health. (WHO, 2013a). Transitioning to adult care is linked with a number of barriers which could be from the individual or from the health facility. Some of the individual barriers include; stigma, drug abuse, mental diseases, attachment to a paediatric healthcare provider and phobia for adult clinics. The health facility factors range from inadequate training and experience of staff in adolescent health issues and a gap in communication between children and adult HIV care services (Straub & Tanner, 2018). In other to have a safe transfer from adolescent to adult care, there is the need for detailed and context specific guidelines that can bridge the gap between paediatric/adolescent and 67 University of Ghana http://ugspace.ug.edu.gh adult clinics to provide care that is not only of quality but continuous and desirable for the new adult who is being transitioned as this likely to make treatment outcomes better (Tanner el al., 2017). Moreover, this study reiterates that, adolescent and adult clinic involvement is necessary given that it reduces gaps in care, provides continuous care that is well coordinated and supports the new adult to adapt to the adult services. Transitioning to HIV care can also be facilitated by developing formal, written transition policies (involving both paediatric and adult teams) . training staff in adolescent development, employing strategies (depending on the context) to ease physical connection of adolescents with adult care services, providing support to children and adult clinics, empowering the adolescents with life skills and health management tips to support adherence to medication and open discussions between paediatric and adult health staff (Straub & Tanner, 2018). 2.14 Global Response to tbe HIV epidemic among adolescents Earlier on. adolescents were either part of the children or adult health services but recently it has been recognised that their health requirements are different from those children or adults (Armstrong el al., 2018). The prominence of adolescents in the health response is seen in recent global health and HIV programs (ibid). Some of these include the United Nations Global Strategy for women, Children and adolescents. This Global Strategy for 2016-2030 seeks to achieve the right to the highest attainable standard of health for all women. children and adolescents. It is believed that by 2030 this target would have been achieved. In addition, another fast track agenda was developed in 2015 jointly by UNAIDS, PEPF AR. WHO. UNICEF and the Elisabeth Glacier foundation. This one was called start free, stay free and AIDS free. It has a number of objectives; 68 University of Ghana http://ugspace.ug.edu.gh _ Eliminating incidence ofHIV infections in children (aged 0-14) by reducing the number of children newly infected yearly to less than 40 000 by 2018 and 20 000 by 2020. _ Providing ARV treatment to 95% of all HIV positive pregnant women by 2018. -Decreasing the incidence of HIV infections among adolescents and young women aged 10-24 to less than 100 000 by 2020. _ Increase voluntary medical circumcision for HIV prevention to 25 million men by 2020, with a focus on young men aged 10-29. _ Provide antiretroviral therapy to1.6 million children (aged 0-14) and 1.2 million adolescents (aged 15-19) living with HIV by 2020 (P. UNAIDS, WHO, UNICEF, Elisabeth Glacier Foundation 2015). Furthermore, another project was launched by UNAIDS and UNICEF in February 2015, called "ALL IN" to end adolescent HIV by 2030. This program was launched in a bit to stimulate global action towards HIV and a population that were largely neglected in the global AIDS response, that is, adolescents. It is focused on the 28 countries that contribute to 86% of all adolescent HIV and seeks to bring adolescents into the limelight as the struggle to end adolescent HIV continues (U. UNAIDS, 2016). The ALL In project has three main objectives: • Reduce incidence of HIV infections among adolescents by at least 75 % • Reduce AIDS-related deaths among adolescents by at least 65% • End stigma and discrimination 2.15. Measurement issues in adherence research Inadequate adherence to antiretroviral treatment leads to therapeutic inefficacy for patients and programmes and clinical failure as well as emergence and transmission of resistant viruses (Kouanfack et al., 2008). Accurate measurement of antiretroviral adherence is therefore essential for targeting and monitoring interventions to increase adherence and 69 University of Ghana http://ugspace.ug.edu.gh prevent emergence of drug resistant viruses (Berg & Amsten, 2006). There are varied methods of measuring adherence with advantages and disadvantages depending on the context and the time. In the absence of directly observed therapy (DOTS), the levels of adherence can only be estimated using other available measures (Gill, Hamer, Simon, Thea, & Sabin, 2005). Some of the available indirect methods of measuring adherence include; self-reports, electronic drug monitoring (EDM), pill counts and pharmacy refill records to obtain medication possession ratio(Berg & Amsten, 2006). Adherence can also be measure directly by measuring metabolites including detection of drugs in plasma. These are reviewed below (ibid). 2.1S.1 Self-Reporting Self-report is the most frequently used adherence measure in both clinical and research settings because it is easier, flexible, affordable with reduced respondent burden and also safes time (Berg & Amsten, 2006). In this method, respondents are usually asked to recall the number of doses skipped within a defined period and adherence is then calculated (Simoni el at., 2006). It may also include qualitative estimates of overall adherence, reporting the number of days of perfect adherence in the past week or month, recalling when the participant or patient last missed a pill and determining the number (or proportion) of doses (or pills) missed (or taken) over a chosen recall period. The disadvantage of this self-report is the ceiling effect, which is usually due to question misunderstanding and recall bias. For instance, a participant could be asked about the number of pills missed and helshe understands to pills, this way adherence will be o\erestimated (ibid). Furthermore, it easier to remember accurately events that happened than those that were forgotten hence there is a chance for adherence to be over-estimated due to recall bias, (Joslyn, Loftus, Mcnoughton, & Powers, 2001). The use of Computer 70 University of Ghana http://ugspace.ug.edu.gh Assisted Self-Interview (CASI), which can may have an audio attachment to accommodate those with low literacy levels, has been shown to improve self-reported adherence. However, there is no evidence to proof the impact of this method on validity or response rate (Johnson et al., 2001). 2.15.2 Pill counts Pill count (counting the pills of patients) is another method of measuring adherence. Pill counts is measured based on number of pills taken to the pills prescribed. Hence, if an individual is prescribed a medication to be taken as 2 tablets 3 times a day for a week, but takes only 2 tablets a day for 2 days, his !her adherence would be 8 / 42 = 19% (Haynes, Ackloo, Sabota, McDonald, & Yao, 2008). There are two types: announced and unannounced counts. Announced pill counts is done during scheduled patient visits as they are asked to bring medication bottles. the pills are counted, and the adherence is calculated with reference to the correct start date. The weakness of announcing is "pill dumping", that is throwing some pills away. Also, if the start date cannot be determined then it will be difficult to calculate the adherence rate. Unannounced pilI counts can be used but some patients may view pill counting as intimidating and indicative of mistrust in their self- reported adherence. Pill count is also very time consuming (Berg & Amsten, 2006). 2.IS.3 Pharmacy Refill Records Pharmacy refill records are used to measure adherence especially in situations where the drugs are provided by a single payer. Adherence rates from pharmacy refill records are calculated either by comparing actual to expected refill dates or by identifying "medication gaps," defined as periods of time during which the patient's supply of medication is assumed to have been over (Inciardi & Leeds, 2005). Pharmacy refill records can be used to measure 71 University of Ghana http://ugspace.ug.edu.gh adherence through the medication possession ratio (MPR) and proportion of days covered (PDC). MPR is calculated as the sum of the days of treatment supplied for all ART prescriptions tilled. within the retlll interval divided by the number of days during that same time period (Kabore el 01 .• 2015; J. Kim. Lee. Park, Bang. & Lee. 2018). A MPR >95% is usually considered adherent. MPR could be more than 100% if patients refill before the medications run out (Jamie, 2010). PDC measures the number of days "covered" by a prescription divided by the number of days in the measurement period (Wang, Huang. & Traubenberg, 2013). The Proportion of days covered takes each day in the interval to see if the patient has the prescribed drug on-hand (ibid). The PDC provides a more conservative measure compared to MPR and avoids double counting days of medication coverage because a day is only counted if all medications are available on that day (Jamie, 2010). The advantage of using pharmacy records to measure adherence is that, the patients are not involved in the measurement and the process takes less time. The main disadvantage is that patients can collect drugs but alone does not equal to taking them. Furthermore, pharmacy retills are not done on time, patients might be missing doses (Berg & Arnsten, 2006). 2.1 SA Therapeutic Drug Monitoring This is another measure of adherence that measures the level of drug in serum (Berg & Amsten, 2006). Low drug level is indicative of non-adherence and virologic failure (ibid). It is not ·.. .. idely used as it is expensive and has challenges with standardization. Therapeutic Drug Monitoring also measures drug level within 24hrs and hence if announced patients can then take their pills and hence the method will over estimate adherence (Paterson, Potoski. & Capitano, 2002). 72 University of Ghana http://ugspace.ug.edu.gh 2.15.5 Composite Measures Some authors have suggested that using composite measures improves sensitivity of adherence measurements (Liu et al., 2001; Lam & Fresco, 2015). This implies that two or more methods can be used to assess adherence in the same population. The difficulty here is which of the methods to combine, how many and even when and where to combine them (Lam & Fresco, 2015). Adherence could also be measured through Electronic Drug Monitoring (EDM), which uses monitoring devices, such as the Medication Event Monitoring System (MEMS). According to Gill and others (Gill et al., 2005), EDM is the best surrogate measure of adherence. In summary, it is clear from literature that the measurement of adherence is still elusive in both clinical and research settings as there are no ideal measures (Adejumo et al., 2014). Self-report is most common and easiest to use. It could be improved upon to increase its sensitivity and specificity. 2.16 Pbilosopbical Underpinnings of tbe Conceptual Framework Health behaviour theories and models have been used in health programs and interventions aimed at improving health outcomes. There are several models that can used to explain and describe interventions in HIV care. Some of these models that are widely used include; the Social Cognitive Theory (SCT), Health Believe Model (HBM), Beliefs about Medicine (BAM) model, the Trans-theoretical model and the theory of reasoned action or planned behaviour. The framework for this study was based on the theory of reasoned action or planned behaviour. The theory of reasoned action was developed by Fishbein and Ajzen in 1975 (Munro, Lewin, Swart, & Volmink, 2007). This theory was first known as the theory of reasoned action (TRA) and later modified to the theory of planned behaviour. The TRA predicts 73 University of Ghana http://ugspace.ug.edu.gh behaviour from intentions and explains the association between attitudes, beliefs, intentions and behaviours that can regulate an individual's behaviour (Adefolalu, 2018). The model is influenced by three factors: norms, attitudes and self-efficacy (Fishbein & Ajzen, 1975). According to Fishbien and Ajzen, behaviour intention is influenced by an individual's attitude towards such a behaviour which is subjective. Self-efficacy is the individual's confidence that they can perform a certain behaviour (Adefolalu, 2018). This theory has been seen to be beneficial in understanding medication adherence in a variety of conditions such as HIV (Vissman, Young, Wilkin, & Rhodes, 2013) in (Rich, Brandes, Mullan. & Hagger, 2015). Adherence in chronic diseases requires a specific pattern of behaviour, that is, performing the behaviour over long periods of time in order to manage the disease as per the recommendations of the health care providers (Sabate & Sabate, 2003). Adherence to ARV requires that the individual takes into consideration the beliefs, attitudes and intentions that exist within a specified population (Adefolalu, 2018). The conceptual framework of the study has been designed to capture adolescents' beliefs, attitudes and behaviours (ranging from demographic, socio cultural to other factors) and how these can affect ability to adhere to ARV drugs. This therefore entails the designing of measures to gauge the intention, that is how likely an individual will adhere to treatment, behaviour which measures previous adherence in the population and predisposition towards adherence (attitude) (ibid). Hence, a comparison of the results between those who are likely to adhere to ART treatment and those who might be non-adherent, will assist in identifying the factors that can determine adherence in a particular study population. However, this theory has been criticized for being static and not accounting for the effect of behaviour on cognition and future behaviour (Sniehotta, Scholz, & Schwarzer, 2005) in (Rich et al., 2015). 74 University of Ghana http://ugspace.ug.edu.gh 2.17 Conceptual Framework The main goal of the study is to assess adherence to ART and its detenninants as well as treatment outcomes among adolescents. The relationship between adherence, its determinants and treatment outcomes among adolescents is conceptualised in Figure 5. Generally, treatment outcomes for HIV are detennined by adherence. Adherence is dependent on a number offa ctors, which have been classified as individual (patient) factors, socio-cultural, socio demographic and health service factors (Hardon et al., 2006). At the individual level, factors like medication side effects, cost of care, inadequate knowledge might adversely affect adherence (ibid). In addition, mental related factors such as depression and anxiety, have been found to adversely affect adherence to ART «Reisner et al., 2009; Petersen et ai., 2010). Socio-cultural factors that may also affect adherence are, for example, beliefs of the guardian or the adolescent and patient's perception of illness. 75 University of Ghana http://ugspace.ug.edu.gh PATIL" FACTORS SOCIG-CliLTh"RAL DE:\K>GRAPmC FACTORS - Side effects FACTORS -Internalized lligrna - Use oft raditional -Age -Beingbusy medicines - Sell -Oth. . iIlIIess -Bm efs in spiritual - LitfJ'acy Le\'e heaJjng - ReliJion - Not mdl!rStmding the rqimen BEALTHSERYIO: FACTORS TREADIE:,\"T - Waiting time ADBERE~CE m;TCOME - Attitude ofbealth staff TO ART OTBER.S FACTORS - Experiencing stigma - Pill burden - Running out of pills - Bting away from home Figure 5: Conceptual framework (Adapted from WHO, 2013) Adherence may also be predicted by demographic factors such as age, sex and education level. Health service factors such as waiting time, attitude of health workers and inadequate trained staff could also affect adherence. Other factors like stigma, social or familial support could also affect adherence (Lall et at., 2015). Some of the factors discussed above may even interact to affect adherence. For instance, patient's perceptions of illness could be affected by demographic factors as well as beliefs and preference for traditional medicines (Hardon et ai., 2006). Adherence for this study is the main determining factor for treatment outcomes. The treatment outcomes assessed in the study are retention rates, viral load suppression and CD4 counts. 76 University of Ghana http://ugspace.ug.edu.gh 2.18 Chapter summary Chapter two has reviewed literature on adherence generally and among adolescents. From the review, adherence has been shown to be generally lower among adolescents than other age groups. However, no study has so far reported ARV adherence rates among adolescents in the North West and South West regions of Cameroon. This chapter went further to review the determinants of adherence to ARV among adolescents. The chapter also reviewed literature on the perspectives of adolescents on adherence, challenges of adherence as well some strategies that could be used to improve upon adherence. The literature review ends with various methods of measuring adherence and a conceptual framework for the study. The next chapter discusses the methods. 77 University of Ghana http://ugspace.ug.edu.gh CHAPTER THREE METHODS 3.0 Introduction This chapter describes the methods that have been used to conduct the study. The chapter gives a detailed explanation of the type of study design. It also describes the study population and the sampling methods. It is also in this chapter that data collection methods, quality assurance, data processing and entry have been explained. Data analysis, study variables and ethical issues are all part of this chapter too. 3.1 Type of Study/Study design The study employed an analytical cross-sectional study design with a record review component. This design was adopted because of the nature of the research objectives. While the cross-sectional study design addressed three of the objectives related to treatment adherence, such a design could not address the objective related to treatment outcomes (retention rates). Therefore. the treatment outcomes were measured retrospectively by reviewing data 011 the cohort of adolescents that were recruited into treatment between January 2015 and December 2015. Indeed, cross-sectional studies have been confirmed to be good when estimating prevalence and investigating associations between an outcome and risk factors (Levin, 2006), such a design is apt for the current study. Moreover, majority of the studies on adherence have used cross-sectional designs, and this strengthened the choice for this design in this current study. 3.2 Study Location!A rea The study was done in Cameroon, a low-income country in Central Africa. Its territory covers nearly 475,650 k m2 (WHO & UN, 2015). Cameroon is boarded by Nigeria to the West, Chad in the North, the Central African Republic to the East and to the South by Congo 78 University of Ghana http://ugspace.ug.edu.gh Gabon and Equatorial Guinea. Cameroon has 10 region with 360 districts and 14 major city councils with an estimated total population of 25,914,285 inhabitants as of 20 17(B U CREP, 2019). The two official languages in Cameroon are English and French. Figure 6 shows the Map of Cameroon with the two study regions indicated in red. MAP OF CAMEROON SHOWING SOUTHWEST. NORTHWEST Figure 6. Map of Cameroon showing North West and South West Regions The population is young, with 64% being aged under 24 years. The population growth rate is 2.6% and life expectancy at birth was estimated at 57.3 years in 2015. Greater than 50% of the youthful population lives in urban areas of Cameroon (ibid). The youthful population is highly unemployed with an unemployment rate of 3.36% in 2018 (ILO, 2019). The Ministry of Public Health coordinates all health services of the country. The health system adheres to the African Health Development guideline based on the district health system. According to this system, the health system is organised into three levels: the 79 University of Ghana http://ugspace.ug.edu.gh operational level, which is the district health service; the intermediate level which is the regional delegations of health and responsible for technical support; and the central level or the ministry of health which functions to oversee the both the district and regional levels as well providing national guidelines for health care delivery in the country. As for the health facilities, they are divided into several categories: the general or regional hospitals which are found in every region hence there are 10 general hospitals, the central hospital in Yaounde, district hospitals in every district, district medical centres and integrated health centres (WHO, 2016b). In Cameroon, the top leading causes of deaths as of 2018 in descending order are HIV / AIDS (14.2%), lower respiratory tract infections (10.5%), malaria (8.8%), neonatal infections (8.5%) and diarrheal diseases (5.0%) (BLICREP, 2019). As regards maternal mortality ratio, it is still high at 590 per 100,000 live births (WHO & UN, 2015). In 2016, there were 560,000 people living with HIV and 37% were on antiretroviral therapy in Cameroon (UNAIDS, 2019). There have been 32,000 HIV related deaths recorded since the year 2000, and 320,000 children have been orphaned by AIDS (WHO, 2014). The initial response by the Cameroonian government to the increasing trends in HIV / AIDS infection was the creation of a National AIDS Control Committee (NACC) to coordinate the National AIDS Programme in 1986. Later in 2000, the first national strategic plan was drawn for HIV to over the period 2000 to 2005. Another national Strategic plan to cover 2006-2010 was later made and implemented accordingly (Mbanya, Sarna, & Tchounwou, 2008). The current national plan covers 2018-2022, and the objectives are based on the 90-90-90 WHO targets for HIV. As regards the use of ARVs, the number of people receiving ARVs treatment increased from 17,156 in 2005 to 168,249 in 2015 indicating an increase of over 10%. Although there was 80 University of Ghana http://ugspace.ug.edu.gh an increase, it was not enough as it was estimated that about 560,000 people were in need of ARVs (WHO, 2016b). It is for this reason that the number ofHIV treatment centres was increased by over 100 additional treatment centres in 2017. For example, initially the South West region had 21 treatment centres but now has 34 and the North West that had 27 now has 39. There is an ongoing plan to have all health facilities providing ARVs to at least HIV positive pregnant women and their children by end of 2018 and this has been partly achieved. 3.2.1 Location of the study Area Cameroon is one of the countries with the highest prevalence ofHIV in the Central African sub-region with a prevalence of 3.7% (PEPFAR, 2018b). It also ranks among the top 20 countries in the world with the highest number of adolescents with HIV (UNICEF, 2015). In this regard, the study selected the North West (NW) and South West (SW) Regions (Figure 7) ofthe country as they have the one of the highest prevalence of HI V in the country 5.1% and 3.8% respectively(PEPFAR, 2018b). These regions form the former British Southern Cameroon that became independent by joining the Republic of Cameroon in 1 October 1961 (Dze-Ngwa, 2015). 3.2.2 Climate Generally, the study area is situated within the humid climatic zone of tropical Africa characterised by two seasons, namely, the wet and dry seasons. The wet season is usually the longest covering at least eight months of the year and runs from Match to October while the dry season spans from November to February. The two regions are located within the Cameroon Volcanic Line (CVL) which is dominated by highlands as a result of active mounting building process from volcanicity. This, together with other determinants such as winds and the closed proximity of the area (especially the South West Region) to the 81 University of Ghana http://ugspace.ug.edu.gh AtlantI,c Ocean hvae g'Iv en th e se remons of study a unique climate often referred to as the o' • Cameroom,a n type 'thin the Koppen Classification System of Climates (Nkemasong. WI 2014). ------------------,,----1 KEY Study Site o Region Capital / Regional Boundary ,.J" ·'own Boundary Figure 7: Map of the North West and South West Regions showing the Study Sites within the Health Districts Average rainfall is generally high ranging from 1700mm in places such as Nkambe to IO,OOOmm in Debundcha, making it the second wettest places in the world after Cherapunji in the foothills of the Alpine Himalayas in India, Like rainfall, temperatures are generally 82 University of Ghana http://ugspace.ug.edu.gh Atlantic Ocean have given these regI.O ns f d0 stu y a uru.q ue climate often referred to as the Camerooru.a n type within the Koppen Classification System of Climates (Nkemasong, 2014). -----------------,,---~ KEY Study Site • Regiun Capilill / Regional Boundary ~ Town Houndary Figure 7: Map ofthe North West and South West Regions showing the Study Sites within the Health Districts Average rainfall is generally high ranging from 1700mm in places such as Nkambe to IO,OOOmm in Debundcha, making it the second wettest places in the world after Cherapunji in the foothills of the Alpine Himalayas in India. Like rainfall, temperatures are generally 82 University of Ghana http://ugspace.ug.edu.gh high throughout the year with places such as Tiko and Muyuka having mean annual temperatures of over 27°C while places such as Kumbo and Ndu have mean temperatures around l"FC (Amawa, 2009). The sustain temperatures alongside the numerous water bodies in these two regions make it an endemic zone for certain communicable diseases especially malaria, typhoid and dysentery which remain key public health concerns in the country. 3.2.3 Socio-Demographic Characteristics According to the 2005 population and housing census whose results were released in 2010, the North West and South West Regions had a total population of over 3.2 million people, making up some 17% of the total population of Cameroon (BUCREP, 2016). This population was broken down into 1,804,695 and 1,384,286 inhabitants for the North West and South West Regions respectively. Nonetheless, given the country's population growth rate of 2.6% and the high fertility rate of3.9, the populations of the two regions under study should be well over 4,017,706 inhabitants, with slightly more than half of the population (52%) residing in urban centres. The populations of the regions are dominated by the females. Socially, the two regions are made up of a multiplicity of ethnic groups including the Bantu, Semi-Bantu and the Fulani ethnic groups. However, given a common colonial history, the regions' educational and legal systems are basically the inheritance of the British systems introduced during the colonial period, particularly after the defeat and dismissal of the Germans in the First World War; that is, between 1919 and 1961 when the area gained independence from Britain by joining the already independent Republic of Cameroon. Religion wise, the area is equally made of a diversity of religious belief systems with the dominant ones bein g Chr' t' . I IS lantty, s I am and African religions. The South West Region is 83 University of Ghana http://ugspace.ug.edu.gh dominated by the Christian religion, partly because of the region's proximity to the Cameroonian coastline which was the point of contact of the early Christian missionaries that began preaching the Gospel of Christ and converting native Africans (Cameroonians) from African religion to Christianity. The North West Region equally has Christians; however, there is a very significant number of Muslim converts as a results of the region's closeness to Northern Cameroon and Nigeria where the spread of Islam was pervasive. 3.2.4 Economic Activities The economic activities in the North West and South West Regions are dominated by agriculture, which employs about 80% of the active age population. The North West Region is characterised by the cultivation of crops and rearing of livestock especially cows, goats and sheep (even though the poultry and piggery livestock sub-sectors have been significantly developed over the past couple of years). Subsistence crop cultivation, mainly for home consumption, is carried out by the semi-bantu ethnic group (and largely involves the women), while cattle rearing is carried out mostly by the Fulanis who have a long track record of pastoralism and is predominantly done by the men. The main crops cultivated in the North West Region are mainly cereals (especially maize, beans, soya bean, cow pea among others), market gardening crops (involving vegetables, green spices, carrots and so on) given that the area enjoys a climate reminiscent of the temperate region, root crops and tree crops. However, a limited degree of plantation agriculture is equally carried out in the area, and this is typical of tea cultivation in Ndu and Ndawara. This is done along other cash crops like Arabica and Robusta coffee. Agriculture in the South West Region is, however, dominated by plantation activities carried out by agro-industrial complexes such as the Cameroon Development Corporation, 84 University of Ghana http://ugspace.ug.edu.gh PAMOL. DELMONTE as well as small holders. The main plantation crops cultivated include palms, banana, rubber and tea among others. There are also farmstead and small- holder plantation schemes involved in coffee and cocoa cultivation as well. Given the dominance of plantation activities in this region. there has been a long-standing record of geographical labour mobility from different parts of Cameroon especially from the North West Region in search of work in these plantations. This mobility has made many towns in the South West Region to be cosmopolitan as they are composed of people from different ethnic and tribal origins. This has also added to the spread of the HIV epidemic in the region. Indeed, given the appalling social conditions which characterise these plantations, there has been high levels of promiscuity and juvenile delinquency, which have all pre-disposed the popUlation to sexually transmitted diseases such as HIV and AIDS. It is in this connection that one of the HIV treatment centres considered in this study is in the Tiko Health District in Tiko Town that grew up largely as a result of palm and banana plantations of the Cameroon Development Corporation. The town is noted for hosting one of the corporation camps of the plantation workers. Away from agriculture, the service sector has equally employed about 20% of the active popUlation. This is dominated by the commercial and transportation sectors. There exists a diversity of commercial activities given the growing urbanisation process (estimated at 52%) in the region (BUCREP, 2010). 3.2.5 Healthcare Services and Infrastructure The North West and South West Regions host a number of health facilities which range from public to private and faith-based health facilities. Each of these regions has a regional hospital in its regional capital. They also have a district hospital in each of the districts 85 University of Ghana http://ugspace.ug.edu.gh within the region, hence the North West region has 7 district hospitals and the South West has six district hospitals. The regional hospitals act as referral centres for all other health facilities within the region. The North West region hosts two of the most renowned faith-based hospitals in Cameroon, namely St. Elizabeth General Hospital and Cardiac Centre, owned by the Catholic Church as well as the Banso Baptist Hospital, which is owned by the Cameroon Baptist Convention. As of2018, the South West Region had 34 HIV operational treatment centres and the North West Region had 39. Most of these centres have at least an adolescent being followed up in care. Five and four health facilities, respectively, were purposively selected from the South West and North West regions for this study. These facilities are briefly described below. 3.2.7 Description of Selected Health Facilities The section of the methods chapter presents a brief description of the selected health facilities; 1. The Regional Hospital Buea: This is the general hospital of the South West region. It serves as the regional referral point to all other health facilities. It has the necessary specialties and serves a target population of 99,286 inhabitants. The hospital is made up of a number of units/departments/centers including the following: the medical unit (male and female), the surgical unit, the paediatrics unit, the maternity unit, the HIV/AIDS unit, the Laboratory unit, the X-ray unit, the hemodialysis center, the Tuberculosis center, the theater and the Diabetes center among others. The Buea Regional Hospital (BRH) serves clients from all over Buea and its environs. These clients either come to the hospital for consultation and treatment or they are referred from other health centers and clinics around. This hospital has a total of 45 HIV positive adolescents registered on treatment. 86 University of Ghana http://ugspace.ug.edu.gh " The Regional Hospital Annex Limbe: This is another major hospital in the South West Region and seconds the main regional hospital as an annex. It serves a target population of 27,814 inhabitants and receives clients from all over Limbe, neighbouring towns and villages. This health facility has the highest number of adolescents on ARV treatment (351) in the South West Region as of2017. Apart from the HIV/AIDS unit, the health facility has other departments: the medical unit, the surgical unit, the paediatric unit, the maternity unit, the laboratory unit, the X-ray unit, the Tuberculosis center, the theater department and the Out-patient department. 3. District Hospital Kumba: This is one of the largest district hospitals in the South West region, which offers consultation, maternity, paediatric, HIV/AIDs care to inhabitants of Kumba and its neighbours. The facility receives over 1000 patients on monthly basis but this has significantly reduced since the Anglophone crisis started. This hospital was recently burnt in February 2019 as a result of the political crisis in the country. It is currently undergoing renovations. At the time data was collected, it had 85 adolescents registered on treatment. 4. The Tiko District Hospital: This is another district hospital in the South West Region. It serves a target population of 5706, and offers consultation, maternity care, laboratory HIV/AlDS services and family planning. It had 20 registered HIV positive adolescents on treatment at the time of this study. 5. The Baptist Hospital Mutengene: This is one of the largest faith-based hospitals in the South West Region. The Baptist Hospital Mutengene (BHM) offers medical, spiritual and psychosocial care, seeing at least 5,000 patients per month with different health problems from various towns in the South West and the Littoral Regions. The hospital 87 University of Ghana http://ugspace.ug.edu.gh coordinates a number of HIV programmes in the region. As of 2018, it had 201 HIV positive adolescents registered on treatment. 6. The Regional Hospital Bamenda: This is the main regional hospital in the North West region and serves the population of Bame nd a and neighbouring villages. It is the referral hospital for all other hospitals in the region. It serves a target population of 41,162. It offers a variety of health services; medical, paediatric, HIV / AIDS, surgical, ophthalmology, dentistry, tuberculosis care, and haemodialysis. It had 78 adolescents registered on treatment in 2018. 7. The Banso Baptist Hospital: This is another faith-based hospital in the North West Region. The Banso Baptist Hospital is a full service hospital with a wide package of activities. It offers health care to an estimate 250-300 patients on a daily basis. Outpatient services include the entire range of family medicine, including prenatal care and childcare. It receives on average 4,000 outpatients on monthly basis with 80-100 deliveries. The Banso Baptist Hospital host a strong HIV programme that has the support of the Cameroon government and the United States government. This HIV program intervenes in community education on HIV and AIDS prevention and treatment, prevention of mother to child transmission ofHIV (PMTCT), prevention and treatment of comorbidities such as tuberculosis (TB), provision of ARV, orphan care, HIV support groups and palliative care for HIV positive persons. However, due to the crisis in Cameroon, the level of activities in this health facility has been greatly reduced. It had 45 adolescents registered on treatment at the time of data collection. 8. The St Elizabeth Hospital and Cardiac Centre Shisong: It is one of the largest faith- based hospitals in the North West region. It also hosts the largest cardiac centre in Cameroon that attracts patients from all over Cameroon and some neighbouring 88 University of Ghana http://ugspace.ug.edu.gh countries. It serves a target population of 17,331 inhabitants. Its activities range from consultation. paediatric, surgery, dentistry, ophthalmology, to HIV care. It had 73 adolescents registered on treatment. Like the Banso Baptist hospital, its functionality has been significantly reduced as a result of the ongoing crisis in the country. 9. The Nkwen Baptist Hospital: This hospital is of the Baptist faith. It is also in the North West region. It serves a population of23,289 inhabitants and offers out-patient services, maternity care, HIV/AIDS care, ophthalmologic and dental services. It offers care to patients in Bamenda town and its environs. As of 2017, it had 92 HIV positive adolescents registered on treatment. 3.3 Study Population This study enrolled adolescents (lO-19years) who were living with HIV and aware of their status. For the cross-sectional component of the study, respondents from among adolescents who were already enrolled in treatment centres and had been on treatment for at least 6 months were recruited. Their records were reviewed from the time of ART initiation up to the time of data collection. For the records review design, the hospital files of adolescents who were initiated in treatment between January 2015 and December 2015 were assessed to obtain data on their retention rates. 3.4 Inclusion and Exclusion criteria 3.4.1 Inclusion Criteria The inclusion criteria of adolescents were as follows: - the adolescent had to be registered on treatment. -he/she should have been on treatment for at least 6 months. -if less than 18years, should have a legal guardian. 89 University of Ghana http://ugspace.ug.edu.gh 3.4.2 Exclusion Criteria Adolescents who were critically ill were excluded from the study. Adolescents who were not aware of their HV status were also excluded. 3.5 Sampling 3.5.1 Sample Size determination The sample size of the study is 460. This was estimated using the Cochrane's formula for calculating sample size for cross-sectional studies as follows: Z 2p(1-P) n= d 2 Where; n= minimum sample size required for the study Z2= critical value, 1.96 p= expected level of adherence (36%) d=precision, which was set at 0.05 The expected level of adherence (self-report) (36%) used was obtained from a 2017 study in Cameroon that measured adherence among adolescents (Fokam et al., 2017). Based on the assumptions above, the minimum sample size estimated was 354. A non-response rate of 30010 was assumed so as to increase the power of the study, and this gave a total sample size of 460. In this regard, 460 adolescents were planned for the study between August 2018 and January 2019. Out of this number, 455 questionnaires were retained giving a response rateof99%. 3.6 Sampling A multistage sampling procedure was followed in this study to select respondents. The process and procedures are described below in detail. 90 University of Ghana http://ugspace.ug.edu.gh 3.6.1 Sampling of Health Facilities A list of health facilities that had HIV treatment centres was obtained from the South West and North West Regional Delegations of Health. As noted earlier, there were 34 treatment centres in the South west region and 39 in the North West. From this list, 9 health facilities were purposively selected based on the number of adolescents registered on treatment. That is, the treatment centres with the highest number of adolescents on treatment were selected. Table 2 shows the estimated number of adolescents on treatment in each of the selected facility as of December 2017 based on data obtained from the HIV Regional Technical Group (RTG) for the North and South West Region. Probability proportionate to size sample allocation was used to obtain the number of adolescents per site (Table 2). Table 2 Number of Adolescents on treatment in the selected Health Facilities Health Facility (HF) Total Number Number Sampled South West Region (SW) Regional Hospital Limbe 351 163 Baptist Hospital Mutengene 201 93 District Hospital Kumba 85 41 Regional Hospital Buea 45 21 District Hospital Tiko 20 9 Total for SW 702 327 North West Region Regional Hospital Bamenda 78 32 Banso Baptist Hospital 45 19 St Elizabeth Hospital Kumbo 73 30 Nkwen Baptist Hospital 92 52 Bamenda Total forNW 228 133 Grand total 990 460 91 University of Ghana http://ugspace.ug.edu.gh 3.6.2 Sampling of Participants For the cross-sectional component of the study, participants were selected using systematic random sampling. For example, if a treatment centre had 63 registered adolescents and 30 participants had to be selected for the study, the 63 was divided by 30 to get the sampling interval which in this case will be 2. The list was numbered starting at 1 and then a random start was selected from say 1. Using the interval of2, participant 3 then 5, 7 and so on were selected until the 30th participant was selected. All the selected participants were then approached on their various clinic days to participate in the study. Participation in the study was voluntary. Some of the participants refused to be part of the study. The main reason for refusal was lack of time to answer the questions. Those who could not participate were not replaced as the sample size estimation had accounted for non-response. As for the records review, data on all the adolescents who started treatment between January 2015 and December 2015 were used. This gave a total of257 adolescents on ART. The year 2015 was selected because retention rates were to be measured at 6, 12 and 24 months. Therefore. two years from 2015 was 2017 which was within the time to obtain 24 months data for the study given that data for this study was collected in 2018. 3.7 Data Collection Methods and Tools 3.7.1 Data collection methods Quantitative data were collected using questionnaires that were administered to the participants individually. Part of the quantitative data were also obtained by using the data extraction fonn. To calculate retention rates, counting and sorting was done on the registers to obtain data on lost to follow up and deaths for the selected cohort of adolescents. Transfer out cases were not included in the calculation for retention rates. 92 University of Ghana http://ugspace.ug.edu.gh 3.7.2 Data Collection tools 1. Questionnaire Questionnaires were used to collect data for the study (see appendix 8). The questionnaire was divided into 9 sections as follows. Section 1: This section had questions on the demographic characteristics of the participants, including age, sex, educational level, occupation, religion, place of residence, living alone or with parent/guardian, means of travel to hospital and distance health facility. The demographic questions were developed by the researcher based on reviewed literature of the possible demographic determinants of adherence. Section 2: This part focused on report to hospital. Participants answered questions on the frequency of hospital visits and reasons why they may skip hospital appointments. They were given a litany of reasons to choose to explain why they missed hospital appointments. Some of the options were transportation problems, financial constraints, being in school or out of town and forgetting among others. Participants could choose more than one reason. Questions from this section were adopted from the AIDS Clinical Trial Group (ACT G) adherence follow-up form. Section 3: This section asked questions on participants' knowledge about drugs as well as adherence levels. Participants were asked if they knew the name of the drug they were taking. If the answer was yes, then they went further to give the name of the drug. They were also asked the daily dosing frequency and the number of pills per day. Participants were also asked if they missed pills in the last 30 days and the number of pills missed. They were further asked on how often they felt difficulties taking their medications on time. Questions for this section were adapted from the CASE (Centre for Adherence Support Evaluation) Adherence Index tool. Questions from this tool were adopted because the 93 University of Ghana http://ugspace.ug.edu.gh questions are simple and could easily be understood by the participants since they were quite young. The CASE adherence index is also a standardised tool which is widely used in self- report measurement of adherence. Section 4: This section was meant to evaluate medication interruptions. Participants were asked to give reasons why they missed medications. Some of the reasons were forgetfulness, avoiding side effects, lost pills, being away from home and religious belief in spiritual healing, to name a few. The questions from this section were adapted from the ACTG adherence form as they are standard and were well suited for the context of the study. Section 5: The fifth section of the questionnaire aimed at probing into reasons for taking medications. The participants were given a wide range of options to select from. Some of the reasons were: taking ARV drugs makes me healthy and taking medications to stay healthy for the family. These were also adapted from the ACTG adherence questionnaire. Section 6: Support from healthcare providers was assessed in this section of the questionnaire. Participants responded to questions about being worried or doubting information they get from hospital staff. They were also asked if they worry about staff not keeping their information private. Some of these questions were adapted from the ACTG questionnaires while others were derived from literature. Section 7: Section 7 was about cost of medications and method of payment. Participants were asked if they pay for drugs. They were also asked the cost of the drug and who paid the cost of the drug for them. Questions from this section were not adapted. They were developed based on the underlying idea of assessing if participants pay for drugs. Section 8: This part of the questionnaire was to evaluate participants for internalised stigma. There were six questions, which the respondents were to respond dichotomously _ agree or 94 University of Ghana http://ugspace.ug.edu.gh disagree. Some of these were about feeling guilty, dirty, worthless or ashamed of the positive HIV status. These questions were adapted from the Kalichman scale, which has been standardised for use in research. Section 9: This is the last part of the questionnaire. It sought participant's opinion on improving adherence. Participants had to respond dichotomously- yes/no to the options for improving adherence which included reducing pills, sending reminder messages and if medications should be brought home. The participants were also given the chance to write other suggestions which could improve adherence. The questions from this section were developed from reviewed literature. The final questionnaire for this study is shown in Appendix 8. 2. Data Extraction form In order to determine the treatment outcomes, a data extraction tool was designed and used. The first section of the form was to obtain clinical information about the patient and some of these were age at first clinic visit, date of ART initiation, if the patient was a transfer case, name of current treatment, if patient had stopped first line treatment and was on second line treatment. The age and sex of the participant were also entered so as to validate the information on age and sex on the questionnaire. The second part of the form was aimed at obtaining information on the patient's previous visits. The dates of the last 10 previous visits were taken. CD4 count information was on the third part of the questionnaire. The last 10 CD4 counts were taken with the dates in which they were carried out. The fourth section was for viral load results and just like for CD4 counts, the 10 most recent results were used. The last part of the form was on the ARV refill dates. The last 12 refill dates were obtained starting with the most recent ones. 95 University of Ghana http://ugspace.ug.edu.gh In summary, each participant was administered one questionnaire and one data extraction form. The questionnaire was interviewer-administered to the participants. The data extraction forms were filled by the research assistant using hospital records. A copy of the data extraction form is shown in Appendix 9. 3. Facility Preparedness checklist To assess facility preparedness towards care of adolescents, the John Snow Inc (JSI) tool for assessing readiness of facilities towards HIV care was used. The tool is composed of 6 main domains: leadership, management of ARVs, programme protocols, experience and staffing, laboratory capacity as well as drug management and procurement. Each domain was scored on a total of 5. Leadership: The domain of leadership had two indicators: the facility's leader and model of care. The first indicator was aimed at evaluating if the health facility had a leader who manages the HIV programme and has experience and/or training in managing ARV programmes. If the facility had no identified leader it was given a score of 1. If the facility had some level of leadership at the level of the facility and the community it was scored 2. The facility was scored 3 if it had a leader with vision and some experience managing healthcare-related interventions, but needed help to start designing and setting up program and protocols. Ifthe facility had a leader with vision and experience managing HIV related healthcare programs who is engaged in establishing an Anti-retroviral program it was scored 4 and scored 5 if there was a leader with experience in the management of the ARV program. The second aspect of leadership was the model of care - the availability of a detailed model of care with operating procedures that have been standardised. A facility which had not identified any possible model of care for the ART program was given a score of I. The facility could have some models of care which could be adapted to ART but needed 96 University of Ghana http://ugspace.ug.edu.gh assistance. In that case. the facility obtained a score of 2. A health facility was scored 3 if it had a model of care but which was not detailed. A score of 4 was obtained by a facility that had a detailed model of care but with operating procedures still being prepared. If the model of care was detailed, fonnalized and approved the facility had a score of 5. The total score for each of the components was calculated and then the average score obtained to have a total score leadership score on 5. ,\[anagement of ARVs: The management of ARVs had four different components- availability of staff for ART, availabil ity of comprehensive services, availability of physical space and the level of community partnership. Each of these components was scored similar to leadership. For ART services, a facility was scored 1 if it had few or no staff in HIV outpatient care or if the staff had not received any training or were inexperience. If the facility had enough staff for HIV care but who were not trained or were inexperienced, it was scored 2. A score of 3 was given to a facility that had staff with some level of training but still inadequate. A facility with staff who had limited experience and might require some training was scored 4. The highest score of 5 was given to a facility that had staff experienced and trained in all areas of HIV care. In the case of comprehensive services, a facility was scored 1 if the HIV care on site or through linkages was not enough. However, if the facility had access to voluntary counselling and testing on site through referral cases, provides HIV care on site but lacks adequate capacity for expansion without assistance, it was scored 2. A facility obtained a Score 00 if it had some HIV services on site and provides treatment for sexually transmitted diseases as well as voluntary counselling and testing. A facility that could provide prevention from mother to child services, more extensive out-patient services for example treatment for tuberculosis but still had gaps in some support services and linkages it was 97 University of Ghana http://ugspace.ug.edu.gh given a score of 4. A facility scored 5 if it had the following aspects, VeT on site and essential support services like counselling, monitoring and adherence support programmes as well as nutrition counselling. Additionally, the facility was supposed to have a full package of services for the treatment of tuberculosis, sexually transmitted infections and other HlV related opportunistic infections. In terms of physical space, if the facility had no defined or confidential space for HIV positive adolescents it was scored 1. A facility that had limited space for the adolescents but with lack of confidentiality obtained a score of2. A facility scored 3 if it had no designated space but with temporal space available as well ongoing plans for a section for adolescents. A score of 4 was obtained if the facility had some space for adolescents which ensured confidentiality but was not enough or limited. A facility with adequate space that ensured the confidentiality of the HIV positive adolescents obtained a score of 5. The last aspect of ARV management was community involvement. A facility scored one if it had no community network or support established. If the facility had started some community mobilisation for support and made arrangements to involve adolescents living with HIV, it was scored 2. A health facility that had made contacts with community leaders and also had some inputs from people living with HIV in such communities obtained a score of 3. Facilities that had already established a network with stakeholders in health, community activists, faith based and non-governmental organisations and performed community needs evaluation had a score of 4. If there was already an existing formal community collaboration with the full involvement of people living with HIV, traditional healers, faith based and non-governmental organisations among others, the facility was score 5. The total score for this section was then obtained and the average score calculated to get the total domain score on 5. 98 University of Ghana http://ugspace.ug.edu.gh Program Protocols, Management and Evaluation: This indicator had three components: ART guidelines, management information systems (MIS), programme monitoring and evaluation. The availability of program protocol was the first indicator on this domain. If a facility had some care protocols but did not have access to the national protocol or guidelines for HIV treatment, it was scored. A facility that had some experience with HIV related guidelines but with no experience on monitoring and evaluation was scored 2. A facility obtained a score of 3 if it had the protocol but not being used or approved by the program management. A score of 5 was obtained if the facility had approved national guideines for HIV screening, eligibility criteria, ARV initiation, clinical and laboratory monitoring and follow-up, management of side effects and treatment failure. Secondly, the management information system was also verified. Facilities with very basic records and no management and information system to track patients was scored 1. If a health facility had a basic management and information system to track patients but with no specific HIV information included, it was scored 2. A facility got a score of 3 if it had some elements of the management and information system but with inadequate capacity for expansion to meet up with the needs of the ARV program as well as needing improvement in medical record keeping. Facilities that had a system of follow-up but with gaps in tracking of patients and charting was scored 4. A score of 5 was obtained if the facility had a system in place for tracking patients, medical records, charting for clinical care and laboratory results with well-defined flow sheets for ART. A total program protocol score was obtained and the mean score calculated to get the domain score on 5. Program monitoring and evaluation was also assessed. A facility that had no procedures for program level monitoring and evaluation was scored 1. If the facility has some procedures or plans for program monitoring and evaluation which were insufficient for the site, it was 99 University of Ghana http://ugspace.ug.edu.gh scored 2. A facility scored 3 if it had some related monitoring and evaluation with some training in monitoring and evaluation but with no specific procedures for ART monitoring and evaluation put in place. A score of 4 was for a facility that, had some plans and procedures for program level monitoring and evaluation and quality improvement for ART but requiring some upgrading. If a facility had a well-established program monitoring and evaluation plan, with process and outcome measures of ARV program with results used for program decision making it was scored 5. Experience and staffing: This is aimed at assessing the facility capacity in terms of human resources. This domain had two components; staff experience and management, training and retention. For staff experience, a facility obtained a score of I if the available staff had limited experience in HIV care with no training as well as no plans in place for staff training or recruitment. If the facility had staff with HIV care experience but with limited ART training and no resources for immediate addition of staff, but with plans to recruit it was scored 2. A facility obtained a score of 3 if they had staff with HIV care experience but with limited training. If a facility had a staff with knowledge and experience in ART with minimum training for prescribing, follow-up and adherence support and counselling it was scored 4. A facility with adequately trained staff that have experience in primary HIV care and ART including drug prescription, follow-up adherence counselling and support was scored 5. Management, training and retention was one the indicators in this domain. A facility that had no plans for training of staff or evaluation of staffing needs was scored 1. A facility that had started developing a plan for staffing but required additional plans with resources for recruiting more staff, training and management obtained a score of 2. If a facility had a staffing plan but with no official procedure for hiring more staff and training, it was scored 3. A facility scored 4 if it had staffing plans put in place and functional but required more 100 University of Ghana http://ugspace.ug.edu.gh additional recruitment and training. The total score was also obtained based on the stage of the facility and the average score per facility calculated on a scale of 5. Laboratory capacity: It had two components aimed at assessing the facility's testing ability and quality standards. For the testing ability, a facility scored 1 if it had limited or no laboratory test for HIV persons as required by WHO or the national protocol and with no quality assurance mechanism. A score of 2 was obtained if the facility had access to the required national or WHO protocols but which are not reliable. If a facility had access to the protocol for screening and monitoring as required by WHO or national protocols, it obtained a score of 3. A health facility with a high laboratory capacity to perform exams such as liver function tests, full blood counts, and kidney function tests, screening and monitoring as per the protocol but not able to run CD4 counts and viral load tests had a score of 4. A score of 5 was for a facility with the full package of tests required by the guidelines including tests for viral load suppression and CD4 count and with constant availability. In the case of quality standards, a facility with no quality standards and no program for equipment maintenance and limited availability of laboratory supplies scored 1. If the facility had poor quality laboratory standards, unreliable maintenance of equipment with a poor quality assurance process in place, it was scored 2. If there was some minimum level of reliable equipment with functional maintenance program and laboratory supply available and the laboratory has some quality standards with irregular compliance it was scored 3. A facility with reliable equipment and a backup plan with a maintenance program in place, performs internal and external quality assessments but with some occasional breaks in service, it was scored 4. The maximum score of 5 was obtained if a facility had internal and external quality assistance, with a maintenance program, reliable equipment and constant availability of reagents and other laboratory supplies. The total laboratory capacity score was also obtained, and the average calculated to get a score on 5 for laboratory capacity. 101 University of Ghana http://ugspace.ug.edu.gh Drug management and procurement: This is the last section of the tool and it had three components; supply chain, pharmacy management and financial resources for AR V and other drug procurement. For the supply chain, a facility with a limited supply chain in place requiring improvement in major areas including ARVs as well as creating a quality assurance for service availability was scored 1. If there was some reliable supply chain that needed improvement in few areas with adaptations to accommodate some requirements for ARVS and limited quality assurance for product availability, it had a score of 2. A facility scored 3 if it had a supply chain in place but needed adaptations for some specific ARV requirements and quality assurance process for product availability was not available. A score of 4 was obtained by a facility that had a secure supply chain but with some needs of technical assistance in inventory management and limited quality assessment for product availability. A facility that had a secure supply chain from supplier to the facility with all the required storage conditions, a quality assurance system with a monitoring system in place for AR V s to prevent any stock outs was scored 5. The second component of this domain was pharmacy management. A health facility with no established procedures for ARV s, no follow up inventory management procedures for all the essential drugs was scored 1. A facility that had no inventory procedures for ARVs but with limited, unreliable inventory management procedures for other essential drugs was scored 2. A score of 3 was obtained by a health facility that had no inventory management for ARVs but with clearly implemented inventory management procedures for other essential drugs. Health facilities that had started the process of having an inventory management procedure for ARVs but which was not yet completed as well as having a developed inventory management process for essential drugs had a score of 4. To obtain a 102 University of Ghana http://ugspace.ug.edu.gh score of 5. the facility should have developed and put in place an inventory management tool and procedure for ARVs which should include forecasting, making calculations for regular stock reports, dispensing and making orders for emergency supplies. The facility was also supposed to have an established inventory management process for other essential drugs. The last section of this domain was to assess financial resources for ARVs and other drug procurement. If a health facility had not identified sources for ARVs, had very limited resources for drug procurement, management of ARV side effects and other complications, with no identified sources for essential drugs, it was scored 1. A facility that had identified limited sources for ARVs, but with limited resources for drug procurement, management of ARV side effects and other complications, with no identified sources for essential drugs was scored 2. If the facility had identified potential sources of funding for the ARV s drugs but yet to complete the arrangements, required more funding to ascertain the availability of other essential drugs, manage medication related side effects and other HIV related opportunistic infections, it had a score of 3. A health facility with a short-term funding for procurement of ARVs with no certain long term assurance of funding, however had adequate supplies of essential drugs, drugs for the management of ARV related side effects and other complications, obtained a score of 4. To get a score of 5, the facility was supposed to have a secured source or sources for AR V s for the short term with a plan for commitment and drug supply for patients for at least one year and follow-up funding. In addition, the facility was supposed to also have adequate supplies of essential drugs, drugs for the management of ARV related side effects and other complications. 103 University of Ghana http://ugspace.ug.edu.gh The total score for this domain was obtained and the mean scored calculated to have the score for drug management and procurement on a 5. The total score for each facility was then calculated on a total of 30. A facility with a score less than 8 is classified as being at stage 1, which implies the facility is at the stage of mobilizing for the programme. A stage 2 facility scored 9-13 score and is the stage of service delivery planning while a stage 3 facility scoredl4-18 and is therefore preparing to begin. Stage 4 is the action stage and is for facilities with a score of 19-24. The final stage is stage 5 and is meant for facilities with a score of 25-30. At this stage, the facility needs support, maintenance and expansion. Table 3 presents a summary of the interpretations for facility score. Table 3: Scoring Summary of the JSI Tool Scoring Stage Meaning 1-8 Program mobilization 9-13 2 Service Delivery and planning 14-18 3 Preparation 19-24 4 Action 25-30 5 Support, Maintenance and expansion 3.8 Quality Control/Assurance 3.8.1 Training of research assistants Two field assistants were recruited to assist in data collection. The two field assistants had bachelor's degree in nursing. The field staff were invited to a two-day workshop where the principal investigator trained them. Firstly, they were made to understand the objectives of the study. They were then given definition of key concepts like adolescents, adherence and treatment outcomes. Secondly, they were trained on sampling of participants at the health 104 University of Ghana http://ugspace.ug.edu.gh facility level. The assistants were further taught on questionnaire administration and data collection from hospital records. They also received training on ethical issues pertaining to the research, how to approach a respondent, obtain consent and how to administer the questionnaire. The assistants were also given lessons on the importance of keeping research information confidential. The training was done before the study commenced. The assessment offacility preparedness for ART care was done by the principal investigator. 3.8 2 Pre-testing of questionnaire The questionnaire was pre-tested at the Buea Road District hospital in the South West region which was not one of the study sites. Five questionnaires were used for pretesting and the feedback from the testing showed a need to adjust aspects of the questionnaire to aid understanding and have a logical flow. This was done before final data collection. To determine the quality of data, some data extraction forms were randomly selected by the principal investigator and cross-checked with original hospital records to be sure of the data. All the questionnaires were verified for correct coding and completeness before processing. 3.9 Data entry and processing The collected data were then entered into excel and saved in a file on a laptop only accessible to the researcher. As back up, the data were also saved in a drop box, so it could be retrieved in case of any losses. The questionnaires after entry were filed and kept in a safe cupboard. 3.10 Variables and measurement Both dependent and independent variables were defined and measured. The dependent variables were two: adherence and treatment outcome. These variables were operationally defined and measured as follows: 105 University of Ghana http://ugspace.ug.edu.gh 3.10.1 Adherence For the purpose of this study, adherence was defined as the patient's ability to take medications as per the prescription. It was determined through self-report oflast missed pills or doses within the last one month. Self-report adherence was measured based on the 30 days recall. It was calculated as the proportion of pills taken to the number prescribed within 30 days. For example, a patient on one pill daily could have missed 2 pills in the past 30 days, hence the adherence of that participant will be 28/30 = 93%. Based on this premise, participants with a self-report score of2:95% were considered adherent. Adherence was also measured through pharmacy records. This calculation from pharmacy records was done based on the Medication Possession ratio (MPR). MPR was calculated as the sum of the days of treatment supplied for all ART prescriptions filled, within the refill interval divided by the number of days during that same time period. A patient was considered as adherent if the MPR was at least 95%. Adherence was coded as a binary outcome variable. The self-report measure has been adopted for use in this study because it is flexible. easy to use and applicable in many contexts and age groups. As for the Medication Possession Ratio, which is from pharmacy refill records, it has also been used to measure adherence as it eliminates the problem of recall bias. 3.10.2 Treatment outcomes The treatment outcomes considered for this study were viral load suppression, retention and CD4 counts Viral load suppression was considered as having the most recent viral load suppression results of less than 1000 copies per mI. The most recent viral load had to be within the past 6 months. Participants with less than 1000 copieslml were considered having suppressed their viral loads. This viral load was extracted from 106 University of Ghana http://ugspace.ug.edu.gh patient's records in the health facility. All the viral load results done were obtained with the dates on which they were done. The retention rate was determined as the proportion of adolescents who remained on treatment after 6, 12 and 24 months since treatment initiation. The ART retention denominator was the number of adolescents on ART excluding the number who transferred out at 6, 12, and 24 months. • CD4 counts were extracted from patient's records. The results of the 10 most recent CD4 count tests done were taken. The cut off 200cells/ul was used to group the participants. Adolescents with counts greater than or equal to 200cells/ul were graded as having high CD4 counts. fhe independent variables were defined as potential determinants of adherence, and were grouped into patient factors, health facility factors, socio-cultural and other factors. These factors have been operationally defined as follows. 3.1 0.3 Patient factors These are factors relating to the individual (adolescent) that might affect adherence. These include medicine related side effects and cost of care. These factors were coded as binary variables • Knowledge was defined as the patient's understanding of the need to take ARV drugs consistently. The participant answered yes/no to taking drugs to stay healthy. • Medicine related side effects were self-reported from questionnaires. The questionnaire had a question on whether side effects are one of the reasons for missing medications. It was coded as binary as the participant answered yes/no. 107 University of Ghana http://ugspace.ug.edu.gh Cost of care was also a binary variable and the questionnaire was used to determine if cost of medications was the reason for missing medications. It was dichotomously coded as yes/no. Internalized stigma: Internalized stigma is that which comes from within an individual and shows how an individual feel, including feeling worthless, guilty or ashamed due to their HIV status (Kalichman et af., 2009). There were six questions on the questionnaire to assess internalized stigma. These questions were adapted from the Kalichman scale of measuring internalised stigma in HIV patients which is standardised and has been validated. An adolescent who agreed to at least three of these questions was experiencing some form of internalised stigma 3.10.4 Health Service factors Health service factors are the determining variables that relate to the health facility activities and staff. They included waiting time and having experienced poor attitude of staff. The questions were all binary and patients answered as yes/no. 3.10.5 Socio-cultural factors These included the use of traditional medicines, beliefs in spiritual healing and the belied that there were no longer in need of drugs. All the socio-cultural characteristics were coded yes/no and the participants answered yes if they had experienced a particular socio-cultural factor. 3.1 0.6 Demographic factors Demographic variables in the context of this study included age, sex, educational level, residence, distance to health facility and living with parent or legal guardian. All these data were obtained from the questionnaire. The exact age was gotten and treated as a continuous 108 University of Ghana http://ugspace.ug.edu.gh variable. Adolescents were also categorised based on their ages as young, middle and late adolescents in some analysis in other to make some specific inferences. Sex was used as a categorical binary variable. The level of education was divided in four categories: primary, secondary, tertiary and no fonnal education. Adolescents were further characterised according to whom they lived with, parent/guardian or living alone. As for distance to health facility it had four options: less than 30 minutes, 30 minutes, and 30 minutes to one hour and above one hour using commercial transportation or walking to a facility. 3.10.7 Other factors These included variables like stigma, frequency of medications, being away from home and running out of pills. Stigma in this case was extemalised or stigma that is from other sources like family, school, media and hospital among others. It was a binary variable coded yes/no. The frequency of medication was measured as the number of times pills were taken per day. As for being away from home, participants answered yes/no if that detennined their ability to take medications. Running out of pills was also a binary variable with the option of yes/no. 3.10.8 Statistical Methods The data were analysed using univariate, bivariate and multivariate statistical analysis methods. Univariate analysis was used to derive proportions of adherence and quantify adherence levels. It was also used to characterize the socio-demographic and other characteristics of the respondents. Bivariate analysis (using chi square tests and Fishers exact tests) was used to assess association between independent variables and adherence. For multivariate analysis, all the variables that significantly predicted adherence at the bivariate analysis were used. This was to obtain a parsimonious model controlling for confounding and effect measure modification. Adjusted odd ratios were reported and a p_ 109 University of Ghana http://ugspace.ug.edu.gh value less than 0.05 was considered statistically significant at a 95% confidence level. All the quantitative analysis was done using STATA 15. The kappa statistics of inter-rate agreement was used to ascertain the difference between adherence as measured by self- report and MPR. The scale is interpreted as follows (Table 4): Table 4: The Kappa benchmark scale Agreement level Interpretation 0.00 Poor agreement 0.0-0.20 Slight agreement 0.21-0.40 Fair agreement 0.41-0.60 Moderate agreement 0.61-0.80 Substantial agreement 0.81-1.00 Almost perfect agreement Source: (Klein, 2017) 3.1 J Ethical ConsiderationslIssues This study followed the ethical requirements. The procedures to ensure ethical considerations are discussed in the following sub-sections of the chapter. 3.11.1 Administrative and Ethical Approval To conduct the study, administrative and ethical approval were sought. Administrative approval was obtained from the Regional Delegation of health at the North and South West Regions of Cameroon where the study was carried out. Letters of approval are attached in appendix 11 and 12 for the North West and South West regions respectively. Approval was also taken from health facility authorities before commencing the study. Ethical approval was received from the Cameroon Baptist Convention (CBC) ethical review board. The approval letter is attached in Appendix 13. 110 University of Ghana http://ugspace.ug.edu.gh 3.11.2 Informed consent Before each potential study participant was interviewed, a written informed consent was obtained. Informed consent was obtained from adolescents who were 18 years and above and from the guardians of adolescents who were less than 18years. The informed consent ionn contained names and telephone numbers of the Principal Investigator and the contact email of the secretary of the Cameroon Baptist Convention Health Service Ethical Committee. Prior to aU interviews, the interviewers reviewed the informed consent form with the participant/guardian. Participants/guardian were to sign the informed consent form before answering the questionnaire. Participants/guardians were informed of the rational of the study, the procedures and length of the quantitative interviews. Also, the benefits and risks of the study and how they were selected to take part in the study were communicated to them. A copy of the signed consent form was given to the participant/guardian and the other one kept by the lead investigator for future reference. The assent form is also included as Appendix 2. 3.U.3 Informed ascent Infonned ascent was obtained from the adolescents who were less than 18years whose guardian had consented for them to participate in the study. The ascent form contained names and telephone numbers of the Principal Investigator and the contact email of the secretary of the Cameroon Baptist Convention Health Service Ethical Committee. Prior to all interviews, the interviewers reviewed the ascent form with the participant. Participants were to sign the ascent form before answering the questionnaire. Participants were informed of the rational of the study, the procedures and length of the quantitative interviews. Also, the benefits and risks of the study and how they were selected to take part in the study were communicated to them. A copy of the signed ascent form was given to the guardian of the III University of Ghana http://ugspace.ug.edu.gh minor and the other one kept by the lead investigator for future reference. The infonned consent fonn has been shown as Appendix 1. 3.11.4 Confidentiality The confidentiality of the participants was protected. The questionnaires and data extraction forms were identified using numbers and codes. Names of participants or their guardians were not taken. All collected questionnaires and data extraction fonns were kept in locked up in a cabinet. For all data entries in the software used, only codes were used to differentiate the entries. Participants have not been reported by names in the resul ts of the study. 3.11.5 Privacy The privacy of participants was ensured. The questionnaires were administered to them while they were waiting to refill drugs in their separate adolescent section. 3.11.6 Benefits The participants and guardians were told that there were no direct benefits for participating in the study and that the care they will be given during their stay in the hospital was not dependent on their participation in the study. However, they were infonned that, the information provided could help us to understand the detenninants of adherence and make possible recommendations to stake holders on how to improve on adherence in adolescents. 3.11.7 Risks No biological samples were collected, and participants were not exposed to any physical danger whilst they took part in the study. They however spent about 15mins of their time answering the questions. Il2 University of Ghana http://ugspace.ug.edu.gh 3.1 1.8 Right to withdraw Respondents' participation in the study was purely voluntary and they could choose not to participate in the study, withdraw consent at any time, and refuse to answer any question in the process of the interview if they decided to do so and it was not compulsory to explain if they choose to withdraw from the study. Participants were informed that their decision not to participate in the study will not affect them negatively in any way. 3.11.9 Data Management and Protection Data from this research was entered into excel and there was a password on the computer assessable only to the PI. There were no names or identifying information on the data entries. 3.11.10 Compensation The participants and their guardians were not paid or given any form of reward for participating in this research. 3.12 Chapter Summary Chapter three has discussed the methods used in the study. It has explained the study design, study area, sample size calculations, sampling, data collection, processing and analysis. The chapter has also explained the study variables and how each was measured. Issues of ethics at administrative and individual level have also been indicated in this chapter. The following chapter therefore presents the results of the collected and analysed data in relation to the study objectives. 113 University of Ghana http://ugspace.ug.edu.gh CHAPTER FOUR RESULTS 4.0 Introduction This chapter presents the results of the study. The first part of the chapter describes the study participants. The levels of adherence to ARVs, determinants of adherence - which are sub- divided into demographic, clinical, socio-cultural, health service and other characteristics that may affect adherence - are then presented. The chapter also examines facility readiness to adolescent HIV care as well as treatment outcomes of adolescents. 4.1 Demographic Characteristics of Participants Table 5 presents results on the socio-demographic characteristics of the study participants. There were more females (55%) than males (45%). The mean age of the participants was 14.8years (SO = ±2.9). A greater proportion of the adolescents (43%) were young (10- 14years). The participants were also categorized based on their occupational status. In this respect, more than half of them were students (63%), while the rest (37%) were working. Additionally, place of residence was used to group the participants and the majority reported residing in urban areas 329 (75%). A greater proportion of the adolescents live with their parents (67%) and majority were Christians (90%). Most of the participants use commercial transportation (which is dominantly taxi) to travel to the treatment centre, taking less than 30 minutes. 114 University of Ghana http://ugspace.ug.edu.gh Table 5: Socio-demographic Characteristics of Participants Characteristics Total Male, n (%) Female, n (%~ Age in years, M (SD) 14.79(±2.92) 14.39(±2.91) 15.10(±2.99) Age categories 10-14 197 (43.3) 101 (22.2) 96 (21.2) 15-17 139 (30.7) 58 (12.7) 81 (17.9) 18-19 118 (25.8) 45 (9.9) 73 (15.9) Missing 1 (0.2) 1(0.2) 0 Total 455 (100) 205 (45) 250 (55) Level of Education None 33 (7.3) 13 (2.9) 20 (4.4) Primary 130 (28.5) 72 (15.8) 58 (12.7) Secondary 268 (58.9) 112 (24.6) 156 (34.3) Tertiary 14 (3.1) 6(1.3) 8 (1.8) Missing 10 (2.2) 3 (0.6) 7 (1.6) Total 455 (100) 206 (45.2) 249 (54.8) Residence Urban 333 (73.1) 152 (33.4) 181 (39.8) Rural 114 (25.1) 48 (10.5) 66 (14.5) Missing 8 (1.8) 3 (0.7) 5(1.1) Total 455 (100) 203 (44.6) 252 (54.4) Occupation In school 365 (80.2) 179 (39.3) 186 (40.9) Working 22 (4.8) 6 (1.3) 16(3.5) Missing 68 (15) 20 (4.4) 48 (10.6) Total 455 (100) 205 (45) 250 (55) Religion None 20 (4.4) 10 (2.2) 10 (2.2) Christian 408 (89.7) 179 (39.3) 229 (50.3) Islam 16 (3.5) 10 (2.2) 6 (1.3) Others 8 (1.8) 4 (0.9) 4 (0.9) Missing 3 (0.6) 2 (0.4) 1 (0.3) Total 455 (100) 205 (45) 250 (55) 115 University of Ghana http://ugspace.ug.edu.gh Characteristics Total Male, n (%) Female, n (%) Category of Persons living with Adolescents. Parents 295(64.8) 139(30.5) 156(34.3) Guardians 144 (31.6) 59(13) 85 (18.7) By myself 8 (1.8) 3 (0.6) 5 (Ll) Missing 8 (1.8) 5 (1.1) 3 (0.7) Total 455 (100) 206 (45.2) 249 (54.8) Transport means Walking 35 (7.8) 18 (3.8) 17 (3.8) Commercial transport 418(91.8) 187 (41) 231 (50.7) Missing 2 (0.4) 1 (0.2) 1 (0.2) Total 455 (100) 205 (45) 248 (55) Time taken to hospital <30minutes 150(33) 78 (17.1) 72 (15.9) 30minutes 84 (18.4) 30 (6.7) 54 (11.7) 31mins - Ihour 140 (30.8) 61 (13.6) 79 (17.2) >1 hour 78 (17.1) 34 (7.5) 44 (9.6) Missing 3 (0.7) 1 (0.2) 2 (0.2) Total 455 (l00) 204 (45) 251 (55) 4.2 Clinical Characteristics Results on clinical characteristics of participants indicated that 82% were on first line regimens of ARVs, while 18% were on second line (see Table 6). Only 3 of the participants (0.7%) were on third line regimen. The average duration of treatment was 67.3months (SD= ±46.6). Duration on treatment was further grouped into three categories as shown in Table 7. About three quarters of them had been on treatment for at least 24 months. The average age of initiation into treatment was 9.3 months. Regarding hospital visits, 47% of the participants visited the hospital every two months. 116 University of Ghana http://ugspace.ug.edu.gh Table 6 Clinical Characteristics of Participants by Sex Characteristic Total, n (%) Male, n (%) Female, n {%! Type of drug First line 352 (77.4) 153 (33.6) 199 (43.7) Second line 75 (16.5) 39 (8.6) 36 (7.9) Third line 3 (0.7) 2 (0.5) 1 (0.2) Missing 25 (5.5) 9 (2) 16(3.5) Total 455 (100) 203 (44.7) 252 (55.3) Duration on treatment (months) M(SD) 67.3 (±46.6) 66.82 (±46.3) 68.15 (±47.4) 6-12 34 (7.6) 14 (3.1) 20 (4.5) 13-22 41 (9) 23 (5) 18 (4) 24+ 380 (83.4) 168 (36.9) 212 (46.5) Total 455 (100) 205 (45) 250 (55) Age at first clinic visit (months) M(SD) 9.27 (±5.12) 8.94 (±5.4I) 9.57 (±4.87) Transfer into present facility Yes 41 (9) 20(4.4) 21 (4.6) No 406 (89.2) 183 (40.2) 223 (49) Missing 8 (1.7) 2 (0.4) 6 (1.3) Total 455 (100) 205 (45) 250 (55) Frequency of hospital visits Once a month 180 (39.6) 60 (13.1) 120 (26.4) Every two months 212 (46.6) 115 (25.3) 97 (21.3) Every three months 49 (l0.8) 24 (5.3) 25 (5.5) Others 8 (1.8) 3 (0.7) 5 (1.1) Missing 6 (1.3) 2 (0.4) 4 (0.9) Total 455 (100) 204 (44.8) 251 (55.2) The drug types used by the participants with their codes and full names have also been shown in Table 7. Most of the participants were on efavirenz based regimens. 117 University of Ghana http://ugspace.ug.edu.gh Table 7 ARV drug types used by participants with their code names Drug type N(%) ARVCode Full Name TDF/3TC/ATV/r Tenolam Atazanavir First and second line 5 (1.2) ABCl3TClEFV Abacalam Efavirenz First and Second line 8 (1.9) ABC/3TC/LPVI r Abacalam Lopirito First and Second line 7 (1.6) ABC/3TC Abacalam Second line 5 (1.2) ABC/ATZ Abacavirl Atazanavir Second line I (0.3) AB C/3TCINPV Abacalam Nevirapine First and second 4 (0.9) ABC/3TCIEFV Abacalam Efavirenz First and second 21 (4.9) AT Z/3TCINVP Atazanavir Nevirapine First and second 40 (9.5) AZT/3TClEFV Douvir Efavirenz First 23 (5.3) AZT/3TCINVP Douvir Nevirapine First 58 (13.7) AZT/3TC/ATV/r Atazanavir-rito First and second 2 (0.6) ABC/3TCINPV Abacalam Nevirapine First and second 4 (0.9) AB C/3TCINPV Abacalam Efavirenz First and second 6 (1.4) AZT/3TClEFV Douvir Efavirenz First 23 (5.3) AZT/3TClNVP Lamivudine Zidovudine First 61 (14.5) Nevirapine AZT/3TC/EFV Lamivudine Zidovudine First 10(2.3) Efavirenz TDF/3TC/LPV/r Tenolam Lopi-rito First and second 3 (0.7) TDF/3TCfLPV IC Tenolam efavirenz Lopi-rito First and second I (0.3) TX Cotrimox TDF/3TC/EFV Tenolam Efavirenz First 144 (33.5) TDF 13TCIA TVT/r Tenofovir Lamivudine First and Second 1 (0.3) Atazanavir DRV/rfDTG/ETV Darunavir Third 3 (0.7) fDolutegravirfEtravine 4.3 Trends in yearly enrolment of participants into treatment Figure 8 shows trends in yearly enrolment of participants into treatment between 2002 and 2018. Generally, the number of adolescents enrolled into treatment on yearly basis has been on the increase albeit fluctuating less than 10 adolescents enrolled in 2002 but by 2016 about 70 were enrolled. 118 University of Ghana http://ugspace.ug.edu.gh 80 70 60 ~e 50 c ~40 ~ § 30 z 20 10 o .J:.."'~'" !>~" ,.!<)~~q,_",OJ ~I:I ~"'~." ~ ~ t'." t'.!o ~ ~q, .,,""- .,,""- ."r;§) .,," .,,<:S" .,,\)- .,," .,," ~ .,,1:1 ~ .,,1:1 .,,1:1 .,,1:1 .,,1:1 .,,1:1 .,,1:1 Year Figure 8: The distribution of adolescents by year enrolled into treatment 4.4 Distribution of Adolescents by Facility The sampled health facilities providing health services to HIV infected adolescents across the study area were also examined. Results show that the Regional Hospital Limbe (RHB) accounted for 35% of the total number of participants in the study (Figure 9). It was followed by the Baptist Hospital Mutengene (20%). The Tiko District Hospital recorded the lowest number, less than 5%. 40 35 C.. 30 ~ 25 S 20 = 15 ~ 10 ~ 5 0 • I • I I • I • .. Figure 9: Participant distribution according to health facility 119 University of Ghana http://ugspace.ug.edu.gh ·1.5 ARV Adherence levels Determining the level of ARV adherence was the first specific objective of the study. The level of adherence to ARV drugs was measured through self-report and medication possession ratio. The results in this regard are presented below. 4.5.1 Self- Report ARV Adherence As noted in chapters two and three, self-report ARV adherence is measured based on a 30- day recall of pills taken. In this study, it was calculated as a proportion of the number of pills taken to the number of pills prescribed within a period of 30 days. Participants with a self-report measure of 95% and above were considered adherent while the non-adherent adolescents had less than 95%. Figure 10 shows the results on self-report adherence. Some 336 (82.96%) of the participants were adherent to ARV treatment and the remaining 69 (17.04%) were non-adherent. Hence, the self-report measure of adherence was 83%. 90% 83% 80% 70% 60% 50% 40% 30% 20% 17% 10% 0% Adherent No•n-adher ent Figure 10: Percentage distribution of participants by Self-Report Adherence 4.5.2 Medication Possession Ratio (MPR) The medication possession ratio (MPR) was calculated as the sum of the days of treatment supplied for all ART prescriptions filled, within the refill interval divided by the number of days during that same time period. Based on this formula, participants with an MPR of95% 120 University of Ghana http://ugspace.ug.edu.gh and above are considered adherent and vi· ce versa. A to tal f 418 adolescents had data for 0 MPR. From the results obtained with the MPR formula, 307 (73.4%) of the participants were adherent whereas III (26.6%) of them were non-adherent. Figure 11 shows adherence as measured using the MPR formula. 80% 73% 70% 60% 50% 40% 30% 23% 20% 10% 0% Adherent Non-adherent Figure 11: Adolescents Adherence levels using the MPR Measure Given that adherence as measured by self- report measure and MPR was 83% and 73.4% respectively. the hypothesis that adherence levels among adolescents was low has been rejected. Adherence was shown through MPR to be lower than the self- report measure. The relationship between the self-report measure and MPR was assessed. Only the participants who had data for both MPR and self-report were considered. A total of 82 participants had missing data on both MPR and self-report adherence. The Kappa statistics was used to assess the level of agreement between the two measures. The level of agreement was 66% (p == 0.54). Based on the Kappa scale, the 66% agreement observed indicated that there is substantial agreement between self-report and the medication possession ratio adherence. For the purposes of this study, the self-report measure will be used for further analysis to assess the determinants of treatment adherence among adolescents since adherence as 121 University of Ghana http://ugspace.ug.edu.gh me asured thro u gh se If- repo rt was hI· g her than that of MPR even though the difference was not statistically significant. Table 8 Relationship between Self-Report adherence measure and Medication Possession Ratio MPR Self-Report Adherent N (%) Non-Adherent N (%) Total Adherent N (%) 232 (74.8) 78 (25.2) 310 Non-adherent N (%) 47 (74.6) 16 (25.4) 63 Total 279 94 373 .... 6 Determinants of Adherence Assessing the detenninants of adherence was the second specific objective of this study. The determinants of adherence were classified into socio-demographic factors, socio- cultural, health service factors, patient factors and other factors. 4.6.1 Socio-demographic factors and Adherence The socio-demographic detenninants of adherence considered in the study were age, sex, educational level. place of residence, religion, travel means to hospital and whether the adolescents lived with their parents, guardians or alone. Only variables with complete entries for both adherence and the particular variable were considered, that is, all missing variables were excluded. Table 9 shows the results from bivariate or chi-square test of independence analysis of the relationship between socio-demographic factors and self- reported adherence. According to the results in Table 9, early adolescents reported the highest adherence with an adherence level of 87.4%. The adolescents with the lowest adherence were those in the age category of 18-19 years with an adherence level of 76.4%. The relationship between age and adherence was statistically significant (p= 0.05). 122 University of Ghana http://ugspace.ug.edu.gh In addition, adherence was compared between male and female adolescents. A higher proportion of males (84.3%) were adherent than their female counterparts (81.7%). However, the difference was not statistically significant (p= 0.49), implying that the observed difference in= adherence between them probably occurred by chance. In terms of participants' level of education, the categories considered included: no formal education, primary, secondary and tertiary education of participants. Adherence was highest among those who were in secondary school (88.1 %). Adolescents who had other forms of education such as vocational training had the lowest adherence (48.5%). The difference in adherence between the educational levels was statistically significant (p < 0.01). Furthermore, the difference in adherence was also compared between adolescents living in urban and rural areas. Rural resident adolescents had higher adherence (83.5 %) compared to those residents in urban areas. However, the observed difference in adherence between urban and rural adolescents was not statistically significant (p= 0.75). Living with parents, guardians or alone was also one of the determining factors of adherence considered. Adolescents living with parents had higher adherence (83.9 %) when compared with those living with a guardian or alone. Adolescents living alone reported the lowest adherence level (62.5%). The difference in adherence was however not statistically significant (p = 0.28). With regard to religion, the same level of adherence (84.6%) was observed across Christians and Muslims. Adolescents who indicated to belong to other religions especially the African religion had the lowest adherence rate of 59.3%. The difference in adherence between the various categories of religion was statistically significant (p =0.03). In terms of means of 123 University of Ghana http://ugspace.ug.edu.gh travel to the hospitals, the same rate of adherence (82.9) was observed irrespective of the means of transport used to get to the treatment facility. Table 9 Relationship between adherence and socio-demographic factors Self-Report Adherence Demographic factor Adherent n (%) Non-Adherent n (%) P-value Age categories of adolescents (in years) lO-14 153 (87.4) 22 (12.6) 15-17 98 (82.4) 21 (17.6) 0.05 18-19 84 (76.4) 26 (23.6) Total 335 69 Sex Male 156 (84.3) 29 (15.7) Female 179 (81.7) 40(18.3) 0.49 Total 335 69 Educational level None 16 (48.5) 17 (51.5) Primary 100 (85.5) 17 (14.5) 0.00 Secondary 207 (88.1) 28 (11.9) Tertiary 9 (69.2) 4 (30.8) Total 332 66 Residence Urban 243 (82.1) 53 (17.9) Rural 81 (83.5) 16 (16.5) 0.75 Total 324 69 Live with Parents 218 (83.9) 42 (16.1) Guardians 108 (82.4) 23 (17.6) 0.28 Alone 5 (62.5) 3 (37.5) Total 331 68 Religion Christianity 307 (84.6) 56 (15.4) Muslim 11 (84.6) 2 (15.4) 0.03 Others 16 (59.3) 11 (40.7) Total 334 69 Travel means Walking 29 (82.9) 6 (17.1) 124 University of Ghana http://ugspace.ug.edu.gh Self-Report Adherence Demographic factor Adherent n (%) Non-Adherent n (%) P-value Commercial transport 306 (82.9) 64 (17.1) 0.70 Total 335 69 Time taken to hospital < 30 mins 109 (76.2) 34 (23.8) 30 mins 61 (88.4) 8 (11.6) 0.07 30 mins-one hour 104 (85.5) 18 14.5) > one hour 60(87) 9 (13) Total 334 69 Notes: Sex, age and means of travel each had 51 participants with missing data, who have been excluded from the analysis. Educational level had 57 entries with missing data, and these have also been excluded. As for place of residence. 62 entries had missing data. Religion and distance to hospital each had 52 missing values. All missing values were excluded from the analysis. ·t,6.2 Health Service factors The relationship between health service factors and adherence is shown in Table 10. The results showed that adolescents who had long waiting time in the hospital had a lower adherence (60.6 %) compared to the others who were not experiencing long waiting time (82.9%). 125 University of Ghana http://ugspace.ug.edu.gh Table 10: Health Service Factors and Adherence Self-Report Adherence Health service Adherent Non- adherent P-value factor n (%) n (%) Experienced long waiting time Yes 37 (60.6) 11 (39.4) No 214 (82.9) 44 (17.1) 0.01 Total 251 55 Experienced poor attitude of hospital staff Yes 23 (62.7) 5 (37.3) No 226 (80.1) 47 (19.9) 0.01 Total 249 52 Notes: Long waiting time had 149 missing values and experienced poor attitude from hospital staff had 154 missing values. All these missing values were excluded from the analysis. This difference in adherence was further shown to be statistically significant (p = 0.01). The attitude of staff was also one of the determinants of adherence among adolescents that were studied. Adolescents who reported experiencing poor attitude from health staff had lower adherence (62.7%) compared to the others (80.1 %). The difference in adherence comparing those who indicated poor attitude from health staff and those who had not experienced such poor attitude was statistically significant (p = 0.01). 4.3.3 Socio-cultural factors and Adherence The use of traditional medicines and religious beliefs were some of the socio-cultural factors of adherence that the study took into consideration. A summary of the relationship between socio-cultural factors and adherence is shown in Table II. Out of the 37 adolescents who reported using traditional medicines, 69.4% were adherent. On the contrary, majority of the participants who were not using traditional medicines (344) had a higher adherence rate of 83.3%. This difference in adherence level was statistically significant (p= 0.01). 126 University of Ghana http://ugspace.ug.edu.gh Likewise. the relationship between religious beliefs and adherence was also examined. Religious beliefs included being healed spiritually or by prayers. The results showed a lower adherence rate (78.3%) among those who had these beliefs as compared to those who did not (82.9%). The difference in adherence was, however, not statistically significant. Some adolescents pointed out that they saw no need for the drugs. In this category, adherence rate (78%) was relatively lower than that of adolescents who said they saw the need for drugs (83.7%). The difference in adherence between them was, however, not statistically significant (p= 0.06). Table 11 Relationship between Socio-cultural factors and Adherence among Adolescents Self-Report Adherence Factor Adherent n Non-adherent P-value (%) n(%) Ever used traditional medicines Yes 25 (69.4) 11 (30.6) No 275 (83.3) 55(16.7) 0.01 Total 300 66 Received spiritual healing before Yes 36(78.3) 10 (21.7) No 277 (82.9) 57 (17.1) 0.25 Total 313 67 Not in need of drugs Yes 71 (78) 20 (22) No 242 (83.7) 47 (16.3) 0.06 Total 313 67 Notes: The use of traditional medicines had 89 missing values while religious beliefs a d t' d of drugs each had 75 missing values. The missing values were all excluded from the ~a~~i~n nee 127 University of Ghana http://ugspace.ug.edu.gh 4.6.4 Patient Factors and Adherence Patient factors may also determine how well the patients adhere to ARV drugs. There are a host of patient factors which determine adherence. In this study, the following patient factors have been considered, namely, medication related side effects, internalized stigma, forgetfulness to take pills, lost pills, busy, tired, waking up early and not understanding the treatment regimen. Medication related side effects was reported by some adolescents to hinder adherence. Out of the 391 adolescents who responded to the question on side effects, 17% reported side effects as one of the reasons for poor adherence. Findings revealed that adherence was lower (66.3 %) among adolescents who experienced side effects compared to adolescents who did not report such effects (85.9 %). The observed difference in adherence was statistically significant (p< 0.01). Furthermore, internalized stigma was also assessed as a determinant. Internalized stigma is that which an individual feel because they have a particular condition, in this case HIV. From the 398 adolescents who responded to the questions, 190 (48%) were experiencing internalized stigma. When adherence levels were compared between those experiencing internalised stigma and those without, it was noted that adolescents who were experiencing internalized stigma were adhering less to treatment compared to their counterparts who were not having any issues of internalized stigma and the difference was statistically significant (p = 0.01). Additionally, being HIV positive does not rule out the possibility of other illnesses among adolescents. Adolescents in this study reported the occurrence of other illness as a reason for poor adherence. It was realized that, adolescents experiencing other form of illnesses were less adherent compared to others who were not ill. Their adherence was 70% compared 128 University of Ghana http://ugspace.ug.edu.gh to 87% for those with no co-morbid conditions. Further analysis showed a statistically significant relationship between adherence to ARVs and having other illnesses (p = 0.0). Waking up early for school or for daily activities was another determinant of adherence that was assessed. A total of 164 adolescents reported waking up early and only half of this number were adherent to treatment. Adherence among adolescents who were waking up early for school, work or other reasons was lower (79.4%) when compared to the other adolescents who did not report waking up early as a problem (83.8%). When the difference in adherence was compared between the two groups, it was not statistically significant (p = 0.28). Lastly, some adolescents had difficulties understanding the treatment regimen and this was also having an effect on their treatment adherence. A greater majority of the adolescents understood the regimen and their adherence was higher (83.9%) compared to those who did not (69.8%). After comparing the difference in adherence using the chi-square-statistics, the observed difference in adherence between the two groups was statistically significant (p=O.02). Table 12 shows the relationship between some patient factors and adherence. 129 University of Ghana http://ugspace.ug.edu.gh Table 12 Relationship between Patient Factors and Adherence Self-Report Adherence Factor Adherent n (%) Non-adherent n (%) P-value Experienced Side effects Yes 45 (66.3) 22 (33.7) 250 (85.9) 43 (14.l) 0.01 No Total 295 65 Experienced internalized stigma Yes 13 3(73.9) 18 (16.l) No 188 (91.3) 47 (8.7) 0.01 Total 321 65 Lost pills Yes 22 (78.6) 6 (21.4) No 289 (82.6) 61 (17.4) 0.60 Total 311 67 Being busy Yes 108 (74) 28 (26) No 206 (88) 38 (22) 0.01 Total 314 66 Had other illnesses Yes 70 (70) 30 (30) No 240 (87) 36 (23) 0.01 Total 310 66 Waking up early Yes 108 (79.4) 28 (20.6) No 202 (83.8) 39 (16.2) 0.28 Total 310 67 Not understanding regimen Yes 30 (69.8) 13 (30.2) No 282 (83.9) 54(16.1) 0.02 Total 312 67 Note: All the patient factors had missing values: experiencing side effects had 95 missing values, experiencing stigma had 69 while losing pills had 77 missing values. Being busy had 75 missing values, having other illnesses had 79, waking up early had 78 and not understanding the treatment regimen had 76 missing values. All these missing values have been excluded from the analysis. 130 University of Ghana http://ugspace.ug.edu.gh ".6.5 Other factors of Adherence The other factors of adherence here included stigma, running out of pills, away from home and frequency of medications. The relationship between adherence and these factors was assessed by bivariate analysis using the chi-square statistics. Table 13 shows a summary of the other determinants of adherence. Table 13: Other Determinants of Adherence Self-Report Adherence Factor Adherent N Non-adherent P-value (%) N (%) Experienced Stigma Yes 107 (72.8) 27 (17.2) No 207 (88.5) 40 (11.5) 0.01 Total 314 67 Number of times pills are taken Once daily 131 (82.4) 28 (17.6) Twice daily 178 (84.8) 32 (15.2) 0.54 Total 309 60 Being away from Home Yes 131 (73.6) 47 (26.4) 0.01 No 169 (89.4) 20 (10.6) Total 300 67 Ran out of pills Yes 24 (54.5) 20 (45.5) 0.01 No 273 (85.9) 45 (14.1) Total 297 65 Note: Experiencing stigma had 74 missing values and the frequency of medication had 86 missing values. Being away from home had 88 missing values and running out of pills had 9These missing values were excluded from the analysis. Stigma (externalised) was reported as one of the reasons for not taking drugs. A total of 391 responded to the question on stigma and 149 of them (38%) indicated that they were stigmatized because of the infection and it was affecting their ability to adhere to treatment. The adherence level of the majority who were not experiencing stigma (88.5%) was higher than adolescents experiencing some form of stigma (72.8%). The difference between the 131 University of Ghana http://ugspace.ug.edu.gh two groups of adolescents in tenns of stigma and adherence was statistically significant (p =0.00). The frequency of medications or number of times pills are taken was also one of the factors of adherence that was assessed. There was no significant difference comparing adherence between adolescents who were on once daily and those on twice daily pills (p = 0.54). Being away from home was also assessed as a determinant of adherent. The relationship with adherence was significant (p < 0.01). Also, running out ofpilIs was significantly associated with adherence. 4.7 Multivariate analysis of tbe determinants of adherence To further examine the detenninants of self-reported adherence, factors that showed statistical association at the bivariate level were pulled into a binary and multiple logistic regression models and odd ratios were estimated. Out of the 28 variables included in the bivariate analysis, 12 showed statistical association with self-reported adherence. These 12 factors were then further examined using binary and multiple logistic regression models. Table 14 shows the results. 132 University of Ghana http://ugspace.ug.edu.gh Table 14 Relationship between Adherence and its Determinants in Multiple Logistil' Regression Analysis Factor Adherent Non-adherent OR 95%CI p- AOR 95% CI p- n (%! n {%) Value Value Education None (Ref) 16(48.5) 17(51.5) Primary Secondary 100(85.5) 17(14.5) 1.26 (0.66.2.4) 0.49 0.71 (0.26, 1.97) 0.51 Secondary 207(88.1) 28(11.9) 0.38 (0.11,0.38) 0.14 0.78 (0.09, 6.14) 0.81 Tertiary 9(69.2) 4(30.8) 0.16 (0.07,0.38) 0.0 0.45 (0.13, 1.58) 0.21 (Age categories (years) 1O-14(Ref) 153(87.4) 22(12.6) 15-17 98(82.4) 21(17.6) 0.67 (0.35, 1.28) 0.23 1.06 (0.38, 2.97) 0.93 18-19 84(76.4) 26(23.6) 0.46 (0.25, 0.87) 0.02 0.67 (0.25, 1.79) 0.43 Experience long waiting time Yes (Ref) 37(60.6) 11(39.4) No 214(82.9) 44(17.1) 2.75 (1.39,5.49) 0.00 2.24 (0.81,6.18) 0.12 Experience poor attitude of hospital staff Yes (Ref) 23(62.7) 11(37.3) No 226(80.1) 47(19.9) 2.73 (1.2,6.2) 0.00 1.01 (0.26,3.84) 0.99 Ever used traditional medicines Yes(Ref) 25(69.4) 11(30.6) No 275(83.3) 55(16.7) 2.2 (1.02,4.73) 0.00 1.00 (0.33,3.07) 0.99 Experienced side effects Yes(Ref) 45(66.3) 22(33.7) No 250(85.9) 43(14.1) 2.96 (1.63, 5.38) 0.00 2.63 (1.14, 6.09) 0.02 133 University of Ghana http://ugspace.ug.edu.gh Factor Adherent Non-adherent OR 95%CI p- AOR 95%Cl /'- n{%} ~ Val," Value Experienced internalized stigma Yes(Ref) 133 (73.9) 18 (16.1) No 188 (91.3) 47 (8.7) 3.69 (2.05,6.64) 0.00 2.51 (1.04, 6.04) 0.04 Being Busy Yes (Ref) 108 (74) 28 (26) No 206 (88) 38 (22) 2.59 (1.51. 4045) 0.00 1.39 (0.67,2.89) 0.38 Had other Illness Yes(Ref) 70 (70) 30 (30) No 240 (87) 23 (36) 2.88 (1.64,4.97) 0.00 1.53 (0.69,3.37) 0.29 Not understanding regimen Yes(Ref) 30 (69.8) 13 (30.2) No 282 (83.9) 54 (16.1) 2.26 (1.\,4.16) 0.02 1.96 (0.71, 5042) 0.19 Felt Stigmatised Yes(Ref) 107 (72.8) 27(17.2) No 207 (88.5) 40 (11.5) 2.87 (1.67,4.92) 0.00 0.92 (0040,2.13) 0.85 Religion Christian(Ref) 307 (84.6) 56 (1504) Muslim 11 (84.6) 2 (15.4) 1.00 (0.22, 4.65) 0.99 1.69 (0.25, 11.08) 0.59 Others 16 (59.3) II (40.7) 0.27 (0.12, 0.6) 0.01 2044 (0.16,37.25) 0.52 Away from home Yes(Ref) 131 (73.6) 47 (26.4) No 169 (8904) 20 (10.6) 3.03 (2.58,9.89) 0.00 1.79 (0.83,3.84 0.14 Ran out of pills Yes(Ref) 24 (54.5) 20 (45.5) No 273 (85.9) 45 (14.1) 5.06 (1.71,5.37) 0.00 2.09 (0.78,5.62) 0.14 Note: ref= reference category; OR = Odds Ratios; AOR=Adjusted Odds Ratios 134 University of Ghana http://ugspace.ug.edu.gh From the multivariate logistic regression analysis, only two variables significantly predicted adherence after potential covariates were adjusted for. These were medication side effects and internalised stigma. The odds of adhering to treatment was relatively higher in those who did not experience side effects compared with those who did experience side effects (AOR=2.6; 95% CI= 1.14, 6.09; P = 0.02). It was also observed that adolescents who did not experience internalized stigma were 2.7 had a higher odds of adhering to treatment (AOR = 2.66; 95% CI .. 1.04,6.04; P = 0.04). Based on these results, hypothesis two which states that, adherence to ART among HIV positive adolescents who are on treatment is determined by demographic and socio-cultural, health service factors has been rejected. ~.8 Determinants of both self-report and the Medication Possession Ratio adherence Earlier analysis had shown that there is a substantial agreement between the two measures of adherence. However, given that there were some discrepancies between the self-report measure and the medication possession ratio, there is need to assess the determinants of adherence when the two measures are combined. For the bivariate analysis, religion, distance to health facility and running out of pills showed statistical association with adherence. These variables were pooled into a multivariate model and none of them showed a significant relationship with adherence after adjusting for other co-variates. Details of these results are presented in Table 15. 4.9 Cballenges of Adherence among Adolescents Adhering to life-long medications like ARV continues to pose challenges especially among adolescents. This study had as part of its objectives to investigate some of the challenges of adolescents who are on ARV medication. Investigations revealed that adolescents face a number of challenges to adherence including stigma (59%), forgetting to take medications t59%), being in school (53%) and tired of taking too many pills (50%). In this regard, hypothesis 3 fails to be rejected as the adolescents were challenged by a number of factors. A summary of the challenges of adherence has been shown in Table 16. l35 University of Ghana http://ugspace.ug.edu.gh Table 15: Detem1inants of both self-report and the Medication Possession Ratio adherence Factor Adherent Non-adherent OR 95%CI p- AO 95%CI p- {SR&MPR~ n {%) (SR&MPR~ D {%} value R vlllue Distance to health facility 30mins(Rej) 71 (53.8) 61 (46.2) Less than 30mins 41 (66.1) 21 (33.9) 1.68 0.89,3.14 0.12 1.53 0.8,3.46 0.24 Between 30m ins to one 76 (66.7) 38 (33.3) I.n 1.02,2.89 0.04 1.55 0.89,2.n 0.12 hour Greater than one hour 43 (67.2) 21 (32.8) 1.76 0.94,3.28 0.08 I.n 0.17,3.09 0.12 Religion Christian(Rej) 216 (64.1) 121 (34.9) Muslim 6 (50) 6(50) 0.56 0.11,2.81 0.48 0.89 0.14,5.55 0.90 Others 9 (39.9) 14 (60.1) 0.31 0.11,0.84 0.02 0.37 0.11,1.11 0.08 Ran out of pills Yes (Rej) 19 (46.3) 22 (53.7) No 185 (63) 108 (37) 1.98 1.03,3.83 0.04 1.91 0.96,3.97 0.11 136 University of Ghana http://ugspace.ug.edu.gh Some other difficulties related to adherence that were noted were: running out of pills, being busy. dislike for tablets, absence of guardian, at work and feelings of rejection. Adolescents further mentioned issues of belief to be healed. taking drugs to make them sick. going to church, not wanting to travel with guardian to be some of the issues they face which can have a negative influence on ART adherence. Table 16 Challenges of Adherence faced by the Adolescents Challenge Frequency (N) Proportion (%) Stigma 202 59 Forgetting to take medications 260 59 Being in school 184 53 Tired of taking medications 198 50 High frequency of pills 159 47 Being out of town 195 47 Having transport problems 139 40 Being busy 150 38 Current Political crisis 150 38 Financial constraints 118 34 Sick 91 27 Not wanting to 65 19 Waiting time 47 14 Running out of pills 44 11 Dislike for tablets 30 9 Poor attitude of hospital starr 28 8 Guardian absent 24 6 At work 4 2 Note: ·The proportions shown on table 16 are based only on the number that responded to each question. Multiple responses were allowed for the challenges of adherence. 4.10 Improving Adberence among Adolescents Given the challenges associated with taking ARV among adolescents, there was a need to explore ways of improving adherence. Figure 12 shows the results on participant's perspectives on how to improve ARV adherence. 137 University of Ghana http://ugspace.ug.edu.gh 80% 69% 69% 70% 64% 60% 50% 40% 32% 30% 20% 10% 0% I Reduce pills Sene! . ",lJinder Medications brought Providers should be messages home friendlier Figure 12: Participant's perspective on improving adherence One of the major challenges earlier mentioned was pill burden. A good number of the adolescents (64%) are of the opinion that adherence could be improved by reducing the frequency of pills to be taken. Some of them even proposed the use of injections, which could last for a month. A few of the adolescents also suggested the use of AR V s in form of implants. Furthermore, more than half of the adolescents (69%) agreed that sending reminder messages via text messages could be a means of making adherence better. This finding was aimed at addressing the earlier challenge related to forgetfulness to take medications. Additionally, healthcare workers bringing medications to their homes was another method of improving adherence that the study evaluated. Findings showed that only 32% of the adolescent agreed to medications being brought to their homes by healthcare workers (see figure 11). This \vas the response with the lowest proportion, which by implication indicates that bringing medications home might not improve on adherence. Moreover, 69% of participants suggested that care providers must be friendly in the care delivery process. This 138 University of Ghana http://ugspace.ug.edu.gh proposal was directly related to the fact that the poor attitude of healthcare providers was one of the challenges associated with adherence . .U 1 Adolescents HIV Treatment Outcomes The treatment outcomes of adolescents with HIV was also assessed as one of the study specific objectives. The outcomes considered were viral load suppression. CD4 counts and retention rates. 4.11.1 Measures of viral load A total of 393 viral load results were extracted from individual adolescent files. The viral load results used were those of the most recent test performed. V iral load measurements were obtained from patients' files using a data extraction form. From the findings, the viral load results ranged from "not detected" to 3,424,122 copies per ml. Adolescents with viral loads less than 1000 copies per ml were considered to have viral load suppression. Based on this grouping, 276 (70.2%) had a suppressed viral load while 143 (29.8%) had viral loads greater than 1000 copies per ml. Figure 13 shows a summary of the viral load results. 70",) 60% 50% 30% 40% 30% 20% 10% 0% Viralload suppressed Viral load not suppressed Figure 13: Viral load suppression among Adolescents 139 University of Ghana http://ugspace.ug.edu.gh 4.11.2 Relationship between Adherence and Viral load Adherence to ARV treatment could affect viral suppression. In fact, having a suppressed viral load may be indicative of good adherence. From the analysis, 215 (61%) of the adolescents who were adherent had a suppressed viral load. It was also seen that 9% of them who were adherent did not have their viral loads suppressed. The observed difference in viral load suppression between those who were adherent and those who were not was statistically significant (pstlinger, 2019). A study by Denison and others in 2015 had reported adherence using self-report and MPR but did not show the level of agreement between the two methods (Denison, Koole. et al., 2015). 5.3 Determinants of adherence among adolescents A number of factors that significantly determined adolescents' adherence were analysed in this study. These adherence determinants are discussed in the section that follows. The determinants of adherence considered were demographic, socio-cultural and health facility related among others. From the bivariate analysis conducted, 12 variables were statistically associated with adherence but after adjustments at the multivariate analysis, only two variables - experiencing side effects and internalised stigma - remained statistically significant. From the results, a majority of the adolescents reported side effects as one of the reasons for failing to take medications and the relationship was significant. After adjusting for other variables, the relationship was still significant with the odds of adherence higher among adolescents who did not experience side effects. This might be because side effects that come with ARVs especially at the start of medications may be acute and may be a reason for failing to take medications. Indeed, the results here are consistent ....; th some earlier studies in Cameroon and Kenya in which medication related side effects were seen to affect 154 University of Ghana http://ugspace.ug.edu.gh adherence (Fonsah et al., 2017; Wambugu et al., 2018). Mabunda and others however had contrasting findings as the authors showed that side effects had no association with adherence (Mabunda, Ngasama, Babalola, Zunza, & Nyasulu, 2019). The higher proportion of adolescents in this study who reported medication-related site effects is however not surprising given that most of the adolescents sampled in this study were on efavirenz based medications. These medications are associated with greater side effects such as nausea, vomiting, headaches, swelling of the face, skin rashes and colourations. Side effects, particularly those which exert physical changes to the body, become an issue as adolescents at their age are very concerned about their physical outlook. Therefore, they may consider skipping the medications to avoid such changes. The experience of internalised stigma also significantly predicted adherence at the multivariate level. Higher odds of non-adherence were observed among adolescents experiencing internalised stigma. Generally, experiences of internalized stigma leads to self- imposed isolation and exclusion from social situations (Kalichman, 20l3). This may cause reduced self-efficacy and depressive symptoms such as disempowerment, helplessness, inability to concentrate, and feelings of negativity and anguish (Brouard & Wills, 2006) cited in (Turan el af., 2016). It is likely that these symptoms make HIV positive adolescents to adhere less to medications. These experiences may also cause depression which has been shown in some studies to predict poor adherence (Fonsah et al., 2017; Wambugu et al., 2018). Furthermore, internalized stigma could also cause forgetfulness, which is a major challenge to adhering to medications. Although the relationship between adherence to ARV and internalized stigma has not been extensively studied especially among adolescents, there is a need to critically consider it given that the other factors like socio-demographic factors 155 University of Ghana http://ugspace.ug.edu.gh and socio-cultural factors that have given been attention in literature, are in many cases, not significantly associated with adherence among adolescents. A few studies have however reported the relationship between internal stigma and adherence in other age groups. One of such is a study among HIV positive women in the United states, which showed a significant association between adherence and internalised stigma (Turan et al., 2016). A number of demographic characteristics were considered. In terms of age, adherence was seen to be highest among early adolescents (87.4%). This confirms findings from Barundi and others in Uganda that reported adherence among adolescents less than l5years to be 89.6% (Nabukeera-Barungi et al., 2015). Adherence may be higher among these younger adolescents because they may be getting constant reminders from parents or guardians to take medications. This is probably an indication that transition to adult care is still not adequate hence the older adolescent who are gradually being transferred to adult care are still facing challenges to adhere to medications. Similar to some earlier studies across sub-Sahara Africa (Nyogea et ai., 2015; Dagli- Hernandez et al., 2016; Mabunda et al., 2019), the relationship between age and adherence in this study was not significant however. A study carried out in Tanzania among adolescents also revealed comparable fmdings with age having no significant relationship with adherence (Martelli et al., 2019). However, some earlier studies had shown a significant relationship between age and adherence (Hudelson & Cluver, 2015). The difference in adherence between male and female adolescents was also considered. Adherence was higher in males even though the difference was not statistically significant. The observed higher adherence in male could be due to the gender roles where females are given more domestic task than the males and hence they can have higher chances of 156 University of Ghana http://ugspace.ug.edu.gh forgetting to take medications when they are overwhelmed with other activities. This is similar to earlier studies (R. Gross et 01.,2015; Nabukeera-Barungi et 01.,2015; Xu, Munir. Kanabkaew, & Le Coeur, 2017) which showed that sex differences did not significantly affect adherence. However, a study by Wiens and others (2012) among Ugandan adolescents showed sex as having an effect on adherence, with adolescent males being more likely to adhere. With respect to level of education, adolescents with secondary education had a higher adherence compared to the others. This could probably be attributed to the fact that education broadens their understanding of the need for medications and hence are more likely to take their pills. These results are indeed not different from those of Denison et al. (2018) in Zambia in which they noted that little or no education was associated with poor adherence. This calls for increased support and more counselling among less educated adolescents, including the use of local languages for some of such adolescents. Also. adolescents who profess other forms of religion other than Christianity and Islam had lower adherence. Belonging to a Christian or Muslim religion probably allows adolescents the chance to believe in God and a hope for a life ahead which entreats them to adhere and live on. Some religious houses also offer spiritual counselling, which could reduce possible depression - a major barrier to adherence. Moreover, adolescents living with parents or guardians also showed higher adherence compared to those living alone. These results are in concordance with those of William and others that showed that living alone was associated with poor adherence (Williams et 01., 2006). This is not surprising because guardians/parents are more likely to give constant support and reminders to such adolescents to take their medications and offer moral support. 157 University of Ghana http://ugspace.ug.edu.gh This is indeed consistent with findings by Kim and others in the United States where adolescents reported that their parent/guardian reminded them to take medications and this helped to improve adherence (Sung-Hee et al., 2014). Adolescents who leave alone may also face other challenges, for example, providing for themselves. Together with other difficulties that come with adolescence, this situation could force such adolescents to be less adherent. In a nutshell, the results of this study showed that although there were important differences in adherence along the different socio-demographic background characteristics of respondents, none of the demographic factors significantly predicted adherence among adolescents. A cross-sectional study in Kenya had reported similar findings (Wambugu et al., 20 18). This is surprising given that these variables were conceptually thought to detemline adherence. However. it is a probable indication that the factors that affect adherence among adolescents are perhaps more than the socio-demographic characteristics that differentiate them. Health service factors that were assessed included long waiting time in the health facility and poor attitude of hospital staff to adolescents during clinic visits. Adolescents who reported that they experienced long waiting time had a lower adherence. However, it surprisingly did not influence adherence in the final analysis. A meta-analysis study showed that long waiting time in hospital is linked to poor adherence (Croome, Ahluwalia, Hughes, & Abas. 2017). A similar study in Kenyan equally noted a significant relationship between waiting time and adherence among adolescents (Wambugu et al., 2018). This could be linked to the fact that waiting to receive care during clinic visits discourages some of them from keeping their hospital appointments and possibly missing refills. Long waiting times in some health facilities in a study in Cameroon has been attributed to limited staff with 158 University of Ghana http://ugspace.ug.edu.gh many adolescents to attend to. There is therefore a need for more staff trained in adolescent care so that this could shorten waiting time. Also, the adolescents could be sub-divided into different groups so that there are fewer adolescents at each visit. This could help reduce waiting times especially in facilities where there are a good number of adolescents on treatment. Poor attitude of hospital staff also affected adherence, although the relationship was not statistically significant. Adolescents who had experienced poor attitudes from hospital staff had a significantly lower adherence. Perceived poor attitude of staff could have resulted from the manner of communication or reaction towards adolescents. This could lead to lack of trust in healthcare providers. Adolescents, especially those with HIV, need more special attention given the psychological stress which they go through. They need trained providers to adequately support in their care. Therefore, facing more difficulties with attitude from staff simply adds to their challenges and can lead to defaulting hospital appointments and refills. The use of traditional medicines, religious beliefs and the belief that drugs were no longer needed are socio-cultural factors considered in this study. Adolescents who noted that they had been using traditional medicines had a lower adherence compared to those who did not use traditional medicine. Nevertheless, the relationship was not statistically significant in the final analysis. This is surprising because the use of traditional medicines in most cases substitutes the use of ARVs as shown in previous research. For example, one study found that using traditional medicines was one of the factors undermining ARV adherence as the patients were secretly consuming the drugs in place of ARVs (Croome et al., 2017). Similarly. Thielman and his team in Tanzania observed a drop in adherence level among patients who were visiting traditional healers (Thielman et aJ., 2014). They further noted 159 University of Ghana http://ugspace.ug.edu.gh that treatment fatigue was one factor that was causing patients to seek alternative forms of medication. However, Gross and others in Zimbabwe had contrasting results, showing that the use of traditional medicines did not have a relationship with adherence (Robert Gross et 01 .• 2015). Lubinga et al 2012 also had similar fmdings in Uganda, where the use of traditional medicines had no significant relationship with adherence (Lubinga, Kintu, Atuhaire, & Asiimwe, 2012). Moreover, these traditional medicines are even used without the knowledge of the healthcare provider and some of them might have antagonistic properties or molecules that could interact with the ARVs. The use of traditional medicines might not have been significant but its use alongside the ARVs by patients should be discouraged. This is because its effect on adherence in this study might have been masked by other factors such as treatment fatigue. This is so because 82% of those who were taking traditional medicines also indicated that they were tired of taking medications. Therefore, adolescents on treatment and their guardians need to receive constant reminders on the implications of taking traditional medicines over ARVs . .\ Iso. the perception that there was no need for drugs anymore was also investigated. The participants who felt there was no need for drugs were less adherent. This could be so because some adolescents who were experiencing side effects felt they did not need drugs anymore. The adolescents who had taken drugs and were feeling better also had the same feeling and this was causing them to neglect their drugs. This study considered the following patient factors: medication related side effects, internalized stigma, lost pills, busy, other illness, waking up early and not understanding treatment regimen. Medication related side effects and stigma have been discussed above. 160 University of Ghana http://ugspace.ug.edu.gh A number of participants indicated that the lost their pills, and the results showed that losing pills affected adherence, albeit the relationship was not statistically significant. Pills can get missing in cases where they are hiding them to ensure privacy. Furthermore, given that some of these adolescents are currently internally displaced as a result of the current socio- political crisis in the English-speaking regions of Cameroon (where the study was carried out), they can equally loss their pills as the refuge places may not allow them the privacy and safety of their medications. Some adolescents also pointed out that they were busy, and this negatively affected adherence. These adolescents could be busy with their daily routines such as schooling, working and carrying out other activities which can get them distracted from taking medications or cause them forget taking the medications. Further analysis showed that most of the adolescents who were leaving alone were also busy and this could possibly be undermining their ability to adhere to medications. This is in line with previous research where being busy was causing adolescents to adhere less to treatment (H. Kim et al., 2017). Another important factor that was considered was the presence of other illnesses. This factor also adversely affected adherence, with sick adolescents reporting lower adherence to treatment. This variable however did not significantly determine adherence after adjusting for confounders and it was surprising because being ill increases the burden of medications and gives room for excuses not to take ARVs. Some of the adolescents went further to indicate that illnesses that cause them to vomit prevent them from taking their pills. These findings were related to those from a study in Yaounde which revealed that adolescents with comorbid conditions had higher odds of non-adherence (Fo nsah et al., 2017). In addition, failing to understand the treatment regimen was also a factor which was shown to significantly affect adherence at the bivariate analysis. The study sampled only 161 University of Ghana http://ugspace.ug.edu.gh adolescents who were aware of their status; however, many of them did not understand why they had to take drugs daily and probably for a life time. Further analysis showed that 56% of the adolescents did not even know the name of the drug they were taking and 6% of these adolescents reported that the ARV drugs were not making them healthy. Hence, health service staff and counsellors have a role to always make sure that adolescents know their medications and have a comprehensive understanding of why it is necessary to take them. These results were in line with those of Denison et a1. (2015) where adolescents were reported to be less adherent because they did not understand the medication (Denison, Koole. et al., 2015). Failing to understand the regimen was hence presenting some mental issues to deal with and could possibly contribute to the lower adherence observed. Aside the patient factors, external stigma was also another possible factor considered that could affect adherence in this study. The link between stigma and adherence was observed to be statistically significant. A good number of adolescents had faced some form of external stigma because they were HIV positive. It occurs in the home, school, and from media. When adolescents are faced with stigma from those people around them like family who are aware of their status, it becomes more devastating given that they rather wish for support and encouragement. This calls for need for more sensitizations on parents/guardians of HI V infected parents on the consequences of stigma on the children. Beyond these parents, this sensitization against stigma should be extended to the general public and media where people can be educated to avoid negative talk and adverts about HIV / AIDS. This results are similar to earlier findings of Wambugu and others in which adolescents who were stigmatised were less adherent to treatment (Wambugu et af., 2018). Furthermore, being away from home was shown to reduce adherence. This is most likely so because there is the possibility to forget pills when leaving home or the conditions of the 162 University of Ghana http://ugspace.ug.edu.gh new environment might not be conducive enough to take pills. A study in Kenya had contrasting results as being away from home had no significant association with adherence (Talam, Gatongi, Rotich, & Kimaiyo, 2008). Additionally, running out of pills also had a significant association as adolescents who reported losing pills were less adherent. An earlier study in Ethiopia showed that running out of pills affected adherence (Tsega, Srikanth, & Shewamene, 2015). In conclusion. the conceptual framework was designed indicating that the determinants of adherence ranged from demographic, socio cultural, patient factors and other factors. The results showed that the factors that determined adherence among adolescents was more than the demographic and socio-cultural factors that differentiate them. Internalised stigma and medication related side effects were the factors that significantly determined adherence. 5.4 Challenges of Adherence in adolescents The challenges to adherence among adolescents were examined. Participants reported a number of challenges related to taking prescribed medications as well as keeping appointments. The most reported challenge to adherence was stigma (externalised). This stigma is experienced beginning from home, to school and sometimes even in health facilities. Some of the adolescents reported they were not allowed at home to play, eat or sleep on the same bed with their peers. Some also indicated they faced overt discrimination at home. These kind of behaviours towards adolescents could easily cause depression and other psychological issues which could cause them not to take pills. Stigma as a barrier to adherence in adolescents has been reported in a number of studies (Kunapareddy et al., 2014; Lawan, Amoie, Jahun, & Abute, 2015; Abubakar et al., 2016; Croome el aI., 2017) (Shubber et al., 2016; Ammon, Mason, & Corkery, 2018). Stigma is still pervasive in HIV care and comes from varied sources. Given the adverse consequences of stigma on HIV 163 University of Ghana http://ugspace.ug.edu.gh positive adolescent's health, it is imperative to include campaigns against stigma in HIV programmes since earlier focus has always been on prevention, screening and treatment. One other major challenge faced by adolescents was forgetfulness to take medication. Earlier studies have also revealed forgetfulness as a barrier to adherence (Kunapareddy et aI., 2014; Sung-Hee et al., 2015; Ankrah et a!., 2016; Croome et al., 2017; Wambugu el ai., 201S). Medications could be easily forgotten because adolescents may be busy, do not have reminders or support systems to remind them to take their medications or they may simply have travelled without the medications. For younger adolescents, guardians still have the duty to remind them daily to take medications. However, for the older adolescents, setting alarms as reminders and some random prompts from the guardian could also solve this problem of forgetfulness. Medication taking could also be associated with some daily task like tooth brushing so that the adolescent gets a self-conscious reminder to take medication once they are brushing their teeth. Being in school was also making it difficult to take medications. Indeed, a study by Abubakar and others in Kenya revealed that attending school affected adherence level among adolescence (Abubakar et al., 2016). Schooling causes adolescents to wake up early, and might not create time to take their medications. This could be worse for adolescents living in boarding schools as lack of secrecy may also hinder taking medications effectively. In these situations, the health staff could work together with the adolescent to find a convenient time for taking medications. For example, for an adolescent who wakes very early for school, the medication time could be adjusted and taken in the evening. Adolescents also noted that they were tired of taking medications. This is consistent with similar earlier studies around Sub-Saharan Africa (Kunapareddy et al., 2014; Maskew et al., 2016; H. Kim et al., 2017; Galea el al., 2018). These earlier studies have noted that the daily 164 University of Ghana http://ugspace.ug.edu.gh uptake of drugs causes fatigue and therefore makes it challenging to adhere to treatment effectively. This treatment fatigue might be commonplace among adolescents who are perinatally infected and have been on drugs for a long time. This also discourages them from taking their drugs. Treatment fatigue has been shown to affect even adults who are on ARV s. For adolescents, some colour changes on the drug containers could give a sense of attraction which might re-awaken the zeal for medications. The current political crisis in Cameroon was also one of the major barriers. A number of adolescents are unable to keep their hospital appointments and sometimes run out of pills. Some of them are internally displaced and are struggling to adapt to the new environment. A few of them complained of lack of food and other social amenities, which complement taking of medications. There is therefore the urgent need for the Cameroon government together in collaboration with the stakeholders involved in the current political crisis to bring it to an end. Furthermore, financial constraints were a challenge for a number of adolescents. Lack of money affects food availability, housing situation and transportation to hospital. Consequently, some of them are unable to attend all hospital appointments and are unable to refill their drugs. Some health facilities through NOOs make provision for snacks to adolescents during clinic visits in order to improve on attendance. However, this is not enough and there is still need for more aid to adolescents on ARV treatment as well as schemes to empower some of the parents to adequately cater for them. Some earlier studies have also reported that food insecurity as a barrier to adherence (Coetzee, Kagee, & Bland, 2015; Abubakar et aI., 2016) Finally, ill health and other co-morbidities like Tuberculosis (TB) were impediments to adherence and about one-third of the participants pointed out that when they are sick it 165 University of Ghana http://ugspace.ug.edu.gh affects their ability to take drugs. Some of the adolescents were on TB treatment in addition to the ARY drugs. This adds to the burden of daily pills. Some studies have also reported co-morbidities as barriers to adherence (Croome el al., 2017; Fonsah el al., 2017). Adolescents with such co-morbid conditions might need extra encouragement from parents/guardian and health staff to sustain more medications as most of these co-morbid conditions do not last for long. 5.5 Adolescent's perspective on adherence Most of the adolescents had a good understanding of adherence to antiretroviral therapy. This was seen in their response in which adherence meant taking medications. This implies that adolescents have received some counselling and advice about medications from the health care givers. This information is important as having a simple understanding of what adherence is could also help them improve on their adherence. This was also confirmed in a further analysis where 70% of the adolescents who had a proper understand of adherence were adherent to treatment. The results also revealed that many of the adolescents were taking the medications correctly because it made them healthy. This understanding also made them more adherent. Furthermore, a good number of them also indicated taking medications for family. This also goes to support the role of family in adherence which has been shown by some authors. For example, Beals el al. examined the role played by older wives and mothers in promoting adher. II: Research Approval Letter from the West West Regional Delegation of Public Health ~EPUBUC OF CAMEROON ~EPUBUQue cu CAME~OUN Pall( - Travail - Potrl~ Peace - Work· Fatherland MINISTERE DE LA SANTE PUBLIQUE MINISTRY OF PUBLIC HEAL TH DELEGA TON REGIONALE REGIONAL DELEGATION DU SUD OUEST FOR THE SOUTH WEST Tel: 233 12 22 62 Regional Delegation Date:~' 2 .KIll 2018 233 32 26 lB Reglonol Fund PD.BOX:281 Bu~ THE REGIONAL DELEGATE E:~fr:n~::hA:E/SWR/RCPHIPSI (~~ / I 0 tf~ TO: MBUWIR Charlotte BONGFEN. Department of Population. FClI11ily and Reproductive Health. University of Ghana SUBJEcr: Administrative Authorization to Colle:ct Research Data After a careful review of this study presented to us by this student, we are sure that medical ethics will be respected as the collection of data will be overseen by trained personnel after the consent of the participant has been obtained. With the clarity of her methodology and in view of the importance of this research in generating important information for the better management of patients, we have no objection to her carrying out her research on UOeterminonts of Adherence and Treatment outcomes Among Adolescents Living with HIV In Suea, Kumba, Limbe and Tiko Health OlstrictsH • I therefore call on the health facilities concerned and the participants to give this student the necessary assistance needed to enable her carryout this study of scientific importance. www.mlnsonte.emlwww.swrdp/l.org 223 University of Ghana http://ugspace.ug.edu.gh Appendi. 12: Ethical Appro"al Letter from Cameroon Baptist Connntion Institutional Rc\ ie\\' Board --------------------_._-- CAMEROON BAPTIST CONVENTION HEALTH BOARD INS11T1JTIONAL REVIEW BOARD Julyl1.2tllB -~BongIon. CoIIagtolHealhSdl!nces. l./nIYeBIyolGlum charlJ!te.lmgIenQyoIIoo.oJIoI ... CBC_ao.dlRBlnlllas-.grll1l8d .~--'1Iio27".My.2018. YnurplUlDcol ... bo ....... lI .... nulBoonImoetingtothe enII19BaardilrfinlllllllRMlllnlan ....... boaenltoyouregardiw.j ... Boord'tdoclslon. _undertIlnINtisil ... lli:8lendaloty--,ilryouroUly. Yooll1USlpr_tI1iolRB """""'"' Iobr to tho IbopbIAdmOiomIor and Chief ........ 0Ifi0w /or ........... to cia lho IIUdy In thai insIlIIIflon(l). llyou ...... .., ... I n .. .-dI""*""", ..... lmmacIaIaIysandU .. IRB .. ..- .".,.;ryiIg"'cllqllljIIIpOIId. ThoBoard.,.. __. torllillUlyfora~""period. ThonIafter.boIonI,uY'l1.2019. you ... pJeaoeCClll1pleil ............. bmllinllfIIIOIIwIicII ... bollladwdto .. emaII and nUn Ito mo. Tho~bm ...... bolllVlewedand~byIheItlslidonllReWlwBoardtxb'tolhe ..... indiondaleol ... amnl8ppIIlOIIIperIod. Tholaoto_aoUlypmllxxlllS 10,OOOda. Ynurpt'*"'>l .... booIIlI!IIIIanedlhe ...... l8ferencalRBproIDcU_.,.,~ID .. shouldlncMle: 1. Tho IRB pmIIx:d runbor 2. _oItheprinclpofln....aigBlDrond 3. F"liIiIalthestudJ. F'tI1IIIy, .. -..:tI,~.""""'"lIldprusonlalionspertalninglolhe_probXlI,mustbo IIlbmiIIodtolwlRSilrpl'01llllbllonappR!VII. PIe8IO feeJ netocooQclmo willi IIII1questiono IOOIorconcems regarding'" above. CopIes tJf .. ~~lhiIpn>pOIIIIlI1IUIbollWll1DmeInlIDZlIaAd1olOQ'll/ayoe-maii CBCHB!RBCIgrMI G!!\ 224 University of Ghana http://ugspace.ug.edu.gh CAMEROON BAPTJST CONVENllON HEALTH BOARD INSTlTUTIONAL REVIEW BOARD Baptist centre. Nkwen. P.O. Il0l1. Bamenda. Northw.! Region January 10. 2019 MbulWCIIarfoIt8Bongf11n, Sc:hocIdPublicHeallh. College of heaIIIt scienoes UnlvellilyatGhIna ~J:Om IRBlludy IIUIIIber:: 1RB201a.t 1 TllfeofProlDc:ol: "DetermInants 01"'-' MllIIuImenI ~-. IdalecentlIivIng willi HIV". IRB approyll dIh: July 77, 2018 IRS upirlllod... ~ 17, 20111 Dear Chat1otte, Your propa8ed ~ Intends 10 _ adhermce and lIB datetnWIanII as wei as InlaImenI outcomes among adolescents Iving YoiIh HIV. The AIdy wi liiio dIII!rmIne adcIescen1I' views on adherence. ThIs Will provide i1IonnaIIon about IhI/r mpacIaIIons, beIeII and suggestioot .. far IS !heir care and II8ues at adIIerenc:e \0 N{VllIr8 concemed. Your study protocol _ ruviIIwad by rnernbarI dille esc HeaIIh BoanIIR9 and ... gI8I1t8d expedIIed approval on 27Ih July, 2018. Your protocol ... presented to Ihe entil1l Bon at our last meeting. The Board aptllD\l8d)IU study. This Is,ourtlnal approvallellllr. Please understand 1IIaI1hII1s1he eIIIIcaI and safely I/IIPfUYII for )IU sIudy. You IIIIIf JII'IIStlIIIthlslRB approvaIletIir to Ihe HoIpitaIAdmIniIIIratIr and ChIef MedIcal 0fIlcer for IJPIlfOVIII \0 do the study In that 1nItitution(8). If you mal!8 any changes In Ihe resean:II pIdIlcoI. please Immediately send the IRS an amendment specifying the changes JII'OIlO'ed. The BoIRl grants IIIIIJRMII for this study for a QI18o)"INI' time period. Thereafter, befoI1I July '0, 2019, you d pIeaIe~ our renewallormIIinaI n!ipOItllilk:ll wi be IIIached 10 111 emaft and return ft to me. The oompIeIed form IIIIIf be I8YIewad and IIppIQWd by the InstltutionaI RevIew BoIRl prior to the expIratfon daIB at the CUII8I1I approyaI period. The fee 10 RlMW.study protocol 1110,000 cia. Your protocol has been aasIgned Ihe abov8 ~ IRS protocol nllTblr. AI COIlllSpOIldence to UI sItouIdlnclude: 1. ThelRBprotocoIl1UITIbef 2. Nameofthe~lnVes1igaIorand 3. Fulltltledthesludy. Finaly, aI abstnJcts, manUsa\pts, posIIn and pre5efltationll pertaIni1g 10 the abov8 protocol, rrust be submitted to the lAB for Pf1I1IUbIicatIo !IJlPIOYiI. Please feel he 10 cxnact me with any questions IIldfor COOOI!II1II regarding the abcM. CcpIe& d aD correspondence ftIGIIdInIIlhIs proposal should be sent 10 me and to ZJta Ad1a 118C181ary, e-mail escHBI 225 University of Ghana http://ugspace.ug.edu.gh Appendix 13: Letter of Support for Ethical Clearance Application UNIVERSITY OF GHANA DEPARTMENT OF POPULATION, FAMILY AND REPRODUCTIVE HEALTH SCHOOL OF PUBLIC HEALTH Ret. No.: .' 6 July 2018 'The Clurinnan Cameroon Baptist Conventiun Health Institutional Review Boord (CllcHll-IRIl) Cmncruoll Dcar Ch.airrnan. APPI.lCATION FOR ETHICAL CLEARANCE J wrilll to support the application of Mbu"ir Charlotle lIongren, 8 PHD Studellt with the Dcptll1n1tmt or Population. Family and Reproductivc IIcahh. University of Ohano, School of Public Heallh. Legon. Hcr pruposallil1ed: wl)et.rmln.n'" of adherence and treatment ontcomes among adoks«nl. Ilvlnl with IIIV In CamenlOu" is "lioched for your review. Your cooperation "ould be very much Ill'preciallld. YoW'S faithfully. pn~~~:;=t (Head of Department) COLUGE OF HEAlTH SCIENCES 226 University of Ghana http://ugspace.ug.edu.gh