SCHOOL OF PUBLIC HEALTH COLLEGE OF HEALTH SCIENCES UNIVERSITY OF GHANA DIET QUALITY AND CARDIOVASCULAR DISEASE RISK FACTORS AMONG PEOPLE LIVING WITH HIV BY: KASIM ABDULAI 10443204 THIS THESIS IS SUBMITTED TO THE UNIVERSITY OF GHANA, LEGON IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE AWARD OF DOCTOR OF PHILOSOPHY DEGREE IN PUBLIC HEALTH OCTOBER, 2020 University of Ghana http://ugspace.ug.edu.gh i DECLARATION I verify that this thesis is the product of my original independent research work and it has not been submitted in whole or in part for any degree. The thesis has been produced through the supervision of Prof. Amos Laar, Prof. Kwasi Torpey, and Dr. Agnes Kotoh. I also certify that the thesis has been written by me and any help received in writing this thesis, and all resources used in this thesis have been acknowledged. KASIM ABDULAI Date Signature 21/10/20 (PhD Candidate) ………………………… ………………………… TEAM OF SUPERVISORS Prof. Amos Laar Date Signature (Principal Supervisor) 22/10/20 ………………………… ………………………… Prof. Kwasi Torpey (Supervisor) Date Signature 22/10/20 ………………………… ………………………… Dr. Agnes M. Kotoh Signature (Supervisor) Date 22/10/2020 ………………………… ………………………… University of Ghana http://ugspace.ug.edu.gh ii ABSTRACT Introduction: With improved life expectancy, people living with HIV (PLHIV) are burdened with cardiovascular diseases (CVD) as a result of prolonged exposure to the traditional risk factors for CVD (smoking, obesity, alcohol, and sedentary lifestyle), and complications associated with HIV infection such as inflammation, endothelial dysfunction, hyper-coagulation, and immune activation. The role of diet and prolonged use of antiretroviral medications (ARVs) in CVD is also well established. Interactions between dietary habits, HIV infection itself, and ART may escalate the risk of developing CVDs among PLHIV. These complex relationships between HIV, diet, and CVD risk factors among PLHIV is yet to be comprehensively studied in Ghana. Aim: To assess diet quality and cardiovascular disease risk factors among ARV-exposed PLHIV. Methodology: A multi-methods study was conducted; a systematic review and meta-analysis, and a facility-based analytical cross-sectional design study. The systematic review and meta-analysis preceded the facility-based analytical cross-sectional study. Cochrane Central, Scopus, PubMed, and Google Scholar databases were systemically searched for papers that compared prevalence of CVD risk factors (diabetes, hypertension, dyslipidemia, and obesity) between PLHIV on ART and PLHIV who are ART-naive in low and middle-income countries (LMIC). Papers that satisfied the inclusion criteria were included in the meta-analysis. Pooled estimates for prevalence were generated using random fixed effects models. The cross-sectional study was conducted among 440 adults living with HIV randomly selected from two hospitals - St. Martins De Porres Hospital and Atua Government Hospital - providing specialized HIV care in the Lower Manya Krobo Municipality of the Eastern Region, Ghana. University of Ghana http://ugspace.ug.edu.gh iii Medline, Cochrane, A structured questionnaire was administered to collect data on socio- demographic information, and lifestyle factors. Dietary intake of participants was measured with a two-day 24-hour recall of their usual food intake (one weekday and one weekend). Individual Dietary Diversity Score (IDDS) was used to measure diet quality of the participants. Height was measured with a stadiometer calibrated to 1.0 cm. Omron Body Composition Monitor and Scale (Model HBF-516) was used to determine weight, Body Mass Index (BMI), percentage muscle mass, percentage body fat, and visceral fat of the participants. Three measurements of participants’ blood pressure were taken at a minute’s interval in the right arm with participants sitting upright using the Omron HEM 907 oscillometric monitor (Matsusaka, Japan). Lipid Profile and blood glucose were checked using LipidPlus Lipid Profile and Glucose Monitoring System and Blood glucose with OneTouch Select glucometer respectively. Mean and standard deviations of continuous variables were determined. Frequencies and percentages were used to describe categorical variables. Univariate, bivariate, and multivariate analyses were conducted using Chi-square test, independent Student’s t-test, binary logistic regression, and ordinal logistic regression. Statistical significance was set at p < 0.05. Data analyses were conducted using SPSS for windows version 20, and Microsoft Excel 2016. Results: Results from the systematic review and meta-analysis showed an association between ART intake and prevalence of hypertension, dyslipidemia, and obesity among PLHIV (p<0.01 for all). Results from the cross-sectional study showed that proportion of PLHIV with high IDDS (diet quality) was about 14 percent, proportion of those having diet needing improvement was 56 percent, whiles about 30 percent actually had low IDDS (poor diet). Prevalence of cardiovascular risk factors including diabetes, hypertension, and dyslipidemia were found to 20.1%, 33.3%, and 63.5% respectively. The average IDDS (diet quality) was significantly higher among PLHIV who University of Ghana http://ugspace.ug.edu.gh iv were hypertensive as compared to PLHIV who were not hypertensive. About 1.4 percent of the participants had high risk of developing CVDs over the next 10 years, 13 percent had intermediate risk, whilst about 86 percent of participants were in the low-risk category of developing CVD over the next 10 years. Conclusion: In conclusion, HIV/AIDS patients should benefit from systematic CVD screening for CVD risk factors alongside their regular counselling and care services. The findings of this study suggest that PLHIV largely have poor diet quality and a very high risk for cardiovascular diseases. Thus, routine screening of PLHIV for both nutritional issues and cardiovascular disease risk at the ART centers/clinics, and effective ART medications may reduce these adverse outcomes and improve the overall quality of life of PLHIV. Key words: HIV, ART, diet, CVD risk factors, Agormanya, Atua. University of Ghana http://ugspace.ug.edu.gh v DEDICATION This research is dedicated to my late father Abdulai Alhassan and my mother Barkisu Yakubu, for their encouragement and prayers, and to my generous sister, Asana Abdulai for her unwavering support. This thesis is also dedicated to my beloved wife Hassana Musah and my adorable daughter Aarifah Mandeiya Kasim. Finally, I dedicate this work to all people living with HIV. University of Ghana http://ugspace.ug.edu.gh vi ACKNOWLEDGEMENT I am most grateful to ALLAH for His favour and love towards me. He has been my main source of support through it all. My heartfelt gratitude goes to my supervisors; Professors, Amos Laar, and Kwasi Torpey and Dr. Agnes Kotoh at the University of Ghana, School of Public Health; Department of Population, Family and Reproductive Health, for their constructive guidance and assistance during this research and thesis work. I am also thankful to the lecturers at 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 wish to acknowledge the help provided by Francis Tawiah Ossom and John Atteh Padi, at St. Martins Hospital, and Omari Yeboah Isaac Jnr. at Atua Government Hospital. I just cannot thank you enough for facilitating my data collection process. Special thanks to all the patients who participated in this study. I also acknowledge with profound gratitude my research assistants, Tetteh Regina Teiko, Mary Sackitey Saakie, Justina Gavor Adeniran, and Rebecca Kwesi for their sacrifices and efforts throughout the data collection period. To Aisha Mahama, Hikmatu Abdulai, Alhassan Ahmed, Ahmed Mohammed Doobia, Gideon Amevinya, Shaibu Tettsie, and Fadlan Yusif, may God richly bless you for your immense contribution to this work. There is hope for the future. My appreciation also goes to my sister, Asana Abdulai, for all her support throughout my study period. I also accord sincere thanks to my wife, Hassana Musah; my daughter, Aarifah Mandeiya; my parents, Abdulai Alhassan and Barkisu Yakubu, the Nasagri Family, the Sonaa family, and all my friends for their moral support and prayers throughout my study period. University of Ghana http://ugspace.ug.edu.gh vii TABLE OF CONTENTS ABSTRACT .................................................................................................................................... ii DEDICATION ................................................................................................................................ v ACKNOWLEDGEMENT ............................................................................................................. vi TABLE OF CONTENTS .............................................................................................................. vii LIST OF FIGURES ..................................................................................................................... xiv LIST OF TABLES ........................................................................................................................ xv LIST OF ABBREVIATIONS ...................................................................................................... xvi OPERATIONAL DEFINITION OF TERMS .............................................................................. xx APPENDICES ........................................................................................................................... xxiii CHAPTER ONE ............................................................................................................................. 1 INTRODUCTION .......................................................................................................................... 1 1.0 Background ...................................................................................................................... 1 1.1 Problem Statement ........................................................................................................... 6 1.2 Research Questions .......................................................................................................... 9 1.3 Objectives ....................................................................................................................... 10 1.3.1 General Objective ................................................................................................... 10 1.3.2 Specific Objectives ................................................................................................. 10 1.4 Conceptual Framework .................................................................................................. 10 1.4.1 Description of Framework Components ................................................................. 11 1.5 Justification/Public health implication of the study ....................................................... 14 1.6 Organization of the Thesis ............................................................................................. 15 CHAPTER TWO .......................................................................................................................... 17 LITERATURE REVIEW ............................................................................................................. 17 2.0 Introduction .................................................................................................................... 17 2.1 HIV and CVDs ............................................................................................................... 17 2.1.1 Epidemiology of HIV ............................................................................................. 17 2.1.2 The burden of CVDs ............................................................................................... 19 2.2 HIV infection, ART, traditional risk factors, and cardio-metabolic risk factors ........... 20 2.2.1 HIV infection and cardio-metabolic risk factors .................................................... 20 2.2.2 ART and cardio-metabolic risk factors ................................................................... 21 2.2.3 Traditional and cardio-metabolic risk factors ......................................................... 22 University of Ghana http://ugspace.ug.edu.gh viii 2.2.3.1 Smoking .............................................................................................................. 22 2.2.3.2 Alcohol ................................................................................................................ 22 2.2.3.3 Obesity ................................................................................................................ 23 2.2.3.4 Physical inactivity ............................................................................................... 24 2.2.4 Cardio-metabolic Risk Factors Among PLHIV ........................................................... 26 2.2.4.1 Cholesterol .......................................................................................................... 27 2.2.4.2 Hypertension ....................................................................................................... 28 2.2.4.3 Diabetes ............................................................................................................... 28 2.2.5 Pathogenesis of CVDs among PLHIV .................................................................... 28 2.2.6 Diet and CVD Risk ................................................................................................. 30 2.2.7 Dietary Intake of PLHIV on ART .......................................................................... 33 2.3 Cardiovascular disease risk estimation .......................................................................... 36 2.4 A systematic review that determines the effect of ART on Cardiovascular Risk Factors among People Living with HIV (PLHIV) in Low and Middle-Income Countries (LMIC) ..... 38 2.4.1 Introduction to Systematic Review ......................................................................... 38 2.4.2 Objectives of the review ......................................................................................... 41 2.4.2.1 Primary Objectives................................................................................................. 41 2.4.2.2 Secondary Objectives .......................................................................................... 41 2.4.3 Systematic Review Methods ................................................................................... 42 2.4.3.1 Settings ................................................................................................................ 42 2.4.3.2 Design.................................................................................................................. 42 2.4.3.5 Search Strategy .................................................................................................... 42 2.4.3.6 Peer review literature .......................................................................................... 42 2.4.3.7 Selection of papers .............................................................................................. 43 2.4.3.8 Data Extraction and management ....................................................................... 46 2.4.3.9 Measurement of effect ......................................................................................... 46 2.4.3.10 Dealing with missing data .................................................................................... 46 2.4.3.11 Data Synthesis ...................................................................................................... 46 2.4.3.12 Sensitivity Analysis ............................................................................................. 47 2.4.3.13 Findings of the systematic review and meta-analysis .......................................... 47 2.4.3.13.1 Study Characteristics ..................................................................................... 47 2.4.3.13.2 Prevalence of the Cardio-metabolic Risk Factors among ART positive and ART-naïve ...................................................................................................................... 48 University of Ghana http://ugspace.ug.edu.gh ix 2.4.3.13.3 Effect of ART on the prevalence of Obesity ................................................. 49 2.4.3.13.4 Effect of ART on the prevalence of Diabetes ............................................... 50 2.4.3.13.5 Effect of ART on the prevalence of Hypertension ........................................ 51 2.4.3.13.6 Effect of ART on the prevalence of High Triglycerides ............................... 51 2.4.3.13.7 Effect of ART on the prevalence of Total Cholesterol (TC)......................... 52 2.4.3.13.8 Effect of ART on the prevalence of High LDL Cholesterol ......................... 53 2.4.3.13.9 Effect of ART on the prevalence of High HDL Cholesterol ........................ 53 2.4.3.14 Discussion of key findings ................................................................................... 54 CHAPTER THREE ...................................................................................................................... 58 3.0 METHODS ........................................................................................................................ 58 3.0 Introduction .................................................................................................................... 58 3.1 Study design ................................................................................................................... 58 3.2 Study Location ............................................................................................................... 60 3.2.1 Research setting ...................................................................................................... 61 3.2.2 Occupation .............................................................................................................. 63 3.2.3 Agriculture .............................................................................................................. 63 3.2.4 District health service ............................................................................................. 64 3.2.5 Description of selected hospitals ............................................................................ 64 3.3 Study population ............................................................................................................ 66 3.4 Inclusion and Exclusion criteria ..................................................................................... 66 3.4.1 Inclusion Criteria .................................................................................................... 66 3.4.2 Exclusion Criteria ................................................................................................... 66 3.5 Study variables ............................................................................................................... 67 3.5.1 Outcome Variables.................................................................................................. 67 3.5.2 Explanatory Variables ............................................................................................. 67 3.6 Sampling......................................................................................................................... 67 3.6.1 Sample size calculation ........................................................................................... 67 3.6.1.1 Sample size calculation using Cochrane formula ............................................... 68 3.6.1.2 Sample size calculation using Statcalc module in Epi Info ................................ 69 3.6.1.3 Selection of participants ...................................................................................... 70 3.6.1.3.1 Probability proportional to size allocation .......................................................... 70 3.7 Data Source and Instrument ........................................................................................... 71 University of Ghana http://ugspace.ug.edu.gh x 3.8 Data Collection Techniques ........................................................................................... 71 3.8.1 Structured Questionnaire ........................................................................................ 71 3.8.2 24- Hour Recall ....................................................................................................... 73 3.8.3 Diet Quality/Individual Dietary Diversity Score .................................................... 74 3.8.4 Body Composition and Anthropometry .................................................................. 75 3.8.5 Blood Pressure Measurement ................................................................................. 76 3.8.6 Biochemical Assessment ........................................................................................ 77 3.8.6.1 Fasting Blood Sugar ............................................................................................ 77 3.8.6.2 Lipid Profile ........................................................................................................ 77 3.8.7 Assessment of 10-year cardiovascular risk ............................................................. 77 3.9 Quality Control/Assurance ............................................................................................. 78 3.9.1 Pre-data collection quality assurance measures ...................................................... 78 3.9.1.1 Protocol registration ............................................................................................ 78 3.9.1.2 Recruitment and Training of field staff ............................................................... 78 3.9.1.3 Pre-testing of questionnaire ................................................................................. 79 3.9.2 Quality assurance measures during study period .................................................... 80 3.9.2.1 Appropriate allocation and selection of the study participants .............................. 80 3.9.2.2 Provide supportive supervision .............................................................................. 80 3.10 Data Processing/Data entry ............................................................................................ 80 3.11 Data Analysis/Statistical Methods ................................................................................. 81 3.12 Ethical considerations .................................................................................................... 81 3.12.1 Ethical and Administrative approval ...................................................................... 82 3.12.2 Informed consent .................................................................................................... 82 3.12.3 Confidentiality ........................................................................................................ 82 3.12.4 Privacy .................................................................................................................... 83 3.12.5 Benefits ................................................................................................................... 83 3.12.6 Safety procedures .................................................................................................... 83 3.12.7 Right to withdraw ................................................................................................... 84 3.12.8 Data Management and Protection ........................................................................... 84 3.12.9 Compensation ......................................................................................................... 85 3.13 Dissemination plan ......................................................................................................... 85 3.14 Chapter Summary .............................................................................................................. 85 University of Ghana http://ugspace.ug.edu.gh xi CHAPTER FOUR ......................................................................................................................... 86 RESULTS ..................................................................................................................................... 86 4.0 Introduction ......................................................................................................................... 86 4.1 Demographic Characteristics of Participants ...................................................................... 86 4.2 Normality test of predictor variables .............................................................................. 88 4.3 Diet Quality of the study participants ............................................................................ 89 4.3.1 Consumption of different food groups by the PLHIV ............................................ 89 4.3.2 (Individual Dietary Diversity Score-IDDS) of study participants .......................... 90 4.3.3 Determinants of Individual Dietary Diversity Score (diet quality) ........................ 91 4.2.3.1 Socio-demographic factors and Individual Dietary Diversity Score (diet quality) 91 4.3.3.2 Individual Dietary Diversity Score (diet quality) and other factors ................... 93 4.3.3.3 Regression of Individual Dietary Diversity Score (IDDS) on predictor factors . 95 4.4 Prevalence of diabetes, hypertension, and dyslipidemia among PLHIV ....................... 97 4.4.1 Prevalence of diabetes............................................................................................. 97 4.4.2 Prevalence of hypertension ..................................................................................... 98 4.4.3 Prevalence of dyslipidemia ..................................................................................... 99 4.4.4 Diabetes prevalence and other factors .................................................................... 99 4.4.5 Determinants of Diabetes ...................................................................................... 101 4.4.6 Hypertension prevalence and other factors ........................................................... 103 4.4.7 Determinants of Hypertension .............................................................................. 108 4.4.8 Association between a Group of Explanatory Variables and Dyslipidemia ......... 110 4.4.9 Determinants of dyslipidemia ............................................................................... 115 4.5 Relationship between Diet Quality and CVD Risk Factors (Dyslipidemia, Hypertension, and Diabetes) ........................................................................................................................... 117 4.5.1 Association between Dyslipidemia Status and IDDS ........................................... 117 4.5.2 Association between Diabetes Status and IDDS .................................................. 117 4.5.3 Association between Hypertension Status and IDDS ........................................... 118 4.6 10-Year Cardiovascular Heart Disease Risk of the PLHIV ......................................... 119 4.6.1 Proportions of the PLHIV that belong to the various FRS levels ......................... 120 4.6.2 Association between a Group of Explanatory Variables and Framingham Risk Score (FRS) ......................................................................................................................... 120 4.6.3 Determinants of Framingham Risk Score (FRS) .................................................. 123 4.7 Chapter Summary ......................................................................................................... 125 University of Ghana http://ugspace.ug.edu.gh xii CHAPTER FIVE ........................................................................................................................ 127 DISCUSSION ............................................................................................................................. 127 5.0 Introduction .................................................................................................................. 127 5.1 Foods consumed by PLHIV ......................................................................................... 127 5.2 Diet quality of PLHIV .................................................................................................. 128 5.3 Factors associated with diet quality among PLHIV ..................................................... 130 5.4 Prevalence of Diabetes ................................................................................................. 134 5.5 Factors associated with Diabetes.................................................................................. 135 5.6 Prevalence of Hypertension ......................................................................................... 138 5.7 Factors associated with Hypertension .......................................................................... 139 5.8 Prevalence of Dyslipidaemia ........................................................................................ 146 5.9 Factors associated with Dyslipidaemia ............................................................................. 147 5.10 Association between IDDS (diet quality) and CVD risk factors ................................. 151 5.11 10-year CVD risk among the PLHIV ........................................................................... 152 5.12 Factors associated with CVD risk among the PLHIV.................................................. 153 5.13 Generalizability and transferability of the study findings ............................................ 157 5.13.1 Generalizability ........................................................................................................ 157 5.13.2 Transferability .......................................................................................................... 157 5.14 Strengths and limitations of the study .......................................................................... 158 5.14.1 Strengths of the study ............................................................................................... 158 5.15 Lessons learned from fieldwork about feasibility .................................................... 159 5.16 What is new from this research; and Implication of the study finding ........................ 160 CHAPTER SIX ........................................................................................................................... 162 CONCLUSIONS AND RECOMMENDATIONS ..................................................................... 162 6.0 Introduction ....................................................................................................................... 162 6.1 Conclusions .................................................................................................................. 162 6.1.1 Diet quality and CVD risk factors among PLHIV ................................................ 162 6.1.2 Prevalence of CVD risk factors (diabetes, hypertension, dyslipidemia) .............. 163 6.1.3 Assessment of 10-year CVD risk among the PLHIV ........................................... 164 6.2 Recommendations ........................................................................................................ 164 6.2.1 Recommendation for policy makers ..................................................................... 164 6.2.2 Recommendation for future research .................................................................... 165 University of Ghana http://ugspace.ug.edu.gh xiii REFERENCES ........................................................................................................................... 166 APPENDICES ............................................................................................................................ 193 University of Ghana http://ugspace.ug.edu.gh xiv LIST OF FIGURES Figure 1. Conceptual framework suggesting plausible mechanisms by which ART, socio-cultural factors, HIV infection, and traditional risk factors may influence cardiovascular disease risk and quality of diet. 14 Figure 2: Schematic presentation of the thesis organization ....................................................................... 16 Fig. 3: Prevalence of HIV among adults aged 15 to 49, 2017, by WHO Regions ...................................... 19 Figure 5: Pooled prevalence of metabolic risk factors among ART naïve and ART patients .................... 49 Figure 6: Obesity prevalence forest plot for PLHIV on ART versus PLHIV but ART-naïve .................... 50 Figure 7: Diabetes prevalence forest plot for PLHIV on ART versus PLHIV but ART-naive .................. 51 Figure 8: Blood Pressure prevalence forest plot for PLHIV on ART versus PLHIV but ART-naïve ........ 51 Figure 9: High Triglyceride prevalence forest plot for PLHIV on ART versus PLHIV but ART-naive ... 52 Figure 10: Total Cholesterol prevalence forest plot for PLHIV on ART versus PLHIV but ART-naive .. 52 Figure 11: High LDL prevalence forest plot for PLHIV on ART versus PLHIV but ART-naive ............. 53 Figure 12: High HDL prevalence forest plot for PLHIV on ART versus PLHIV but ART-naïve ............. 54 Figure 13: Study setting .............................................................................................................................. 62 Figure 14: Consumption of different food groups in the previous 24 hours of the study .......................... 90 Figure 15: Prevalence of diabetes ............................................................................................................... 98 Figure 16: Prevalence of hypertension ...................................................................................................... 98 Figure 17: Prevalence of dyslipidemia ........................................................................................................ 99 Appendix 2: Information Sheet ................................................................................................................. 194 Appendix 3: Medical Report Form ............................................................................................................ 196 Appendix 4: Ghana Health Service Ethical Clearance Letter .................................................................... 197 Appendix 5: Letter of Introduction, St. Martins Hospital ......................................................................... 198 Appendix 6: Consent Form........................................................................................................................ 199 Appendix 7: Interpreter’s Statement ........................................................................................................ 200 Appendix 8: Investigator Statement and Signature .................................................................................. 201 Appendix 9: Statement of Witness ........................................................................................................... 202 Appendix 10: Questionnaire ..................................................................................................................... 203 University of Ghana http://ugspace.ug.edu.gh xv LIST OF TABLES Table 1: Lifestyle and cardio-metabolic risk factor analysis ....................................................................... 26 Table 2: Keywords used in literature search ............................................................................................... 42 Table 3: Study Characteristics in the study ................................................................................................. 47 Table 4: Sample size calculation for objectives 2, 3, and 5. ........................................................................ 68 Table 5: sample size calculation for objectives 4. ....................................................................................... 69 Table 6: Selection of study participants ...................................................................................................... 70 Table 7: Individual dietary diversity score guide ........................................................................................ 75 Table 8: Socio-Demographic Characteristics of Participants ...................................................................... 87 Table 9: Association between Socio-Demographic Variables and Individual Dietary Diversity Score (IDDS) .................................................................................................................................................................... 91 Table 10: Association between A Group of Explanatory Variables and Individual Dietary Diversity Score (IDDS) .......................................................................................................................................................... 94 Table 11: Ordinal logistic regression of IDDS on predictor factors ......................................................... 96 Table 12: Association between a Group of Explanatory Variables and Diabetes ..................................... 100 Table 13: Binary logistic regression of diabetes and other factors........................................................... 102 Table 14: Association between a Group of Explanatory Variables and Hypertension ............................. 105 Table 15: Binary logistic regression of hypertension on other factors ..................................................... 109 Table 16: Bivariate analysis of Dyslipidemia and other factors ................................................................ 112 Table 17: Binary logistic regression of dyslipidemia on other factors ...................................................... 116 Table 18a: Independent t-test descriptive statistics ................................................................................. 118 Table 18b: Independent t-test inferential statistics ................................................................................. 119 Table 19: Framingham Risk Score category .............................................................................................. 120 Table 20: Bivariate analysis of Framingham Risk Score (FRS) and other factors ...................................... 122 Table 21: Ordinal logistic regression of FRS on predictor factors ............................................................. 124 University of Ghana http://ugspace.ug.edu.gh xvi LIST OF ABBREVIATIONS ACC American College of Cardiology ACSM American College of Sports Medicine AHA American Hearts Association AHEI Alternative Healthy Eating Index AIDS Acquired Immunodeficiency Syndrome AMD Alternative Mediterranean Diet AND Academy of Nutrition and Dietetics APO A Apolipoprotein A APO B Apolipoprotein B ART Antiretroviral Therapy ARVs Antiretroviral medications BMI Body Mass Index BP Blood Pressure CDC Center for Disease Control and Prevention CHD Coronary Heart Disease CVD Cardiovascular Diseases D. A.D Data Collection on Adverse events of Anti- HIV Drugs University of Ghana http://ugspace.ug.edu.gh xvii DASH Dietary Approach to Stop Hypertension DDS Dietary Diversity Scores DHA Docosahexaenoic acid EPA Eicosapentaenoic acid FA Fatty Acids FAO Food and Agricultural Organization FBG Fasting blood glucose FFQ Food Frequency Questionnaires FRS Framingham Risk Score G D P Gross Domestic Product GHS Ghana Health Service HALS HIV Associated Lipodystrophy Syndrome HDL High-Density Lipoprotein HDL-C High Density Lipoprotein Cholesterol HEI Healthy Eating Index HIV Human Immunodeficiency Virus HR Hazard Ratio HSS HIV Sentinel Survey University of Ghana http://ugspace.ug.edu.gh xviii HTN Hypertension IDDS Individual Dietary Diversity Score IPAQ International Physical Activity Questionnaire LDL Low-Density Lipoprotein LMIC Low and Middle-Income Countries MDS Mediterranean Diet Score MMDAs Metropolitan, Municipal, and District Assemblies MS Metabolic Syndrome NCD Non-Communicable Diseases NCEP National Cholesterol Education Program NIH-AARP National Institutes of Health and American Association of Retired Persons NNRTI Non-nucleoside reverse transcriptase inhibitors NRTIs Nucleoside/Nucleotide Reverse Transcriptase Inhibitors PI Principal Investigator PLHIV People living with HIV PUFAs Polyunsaturated fatty acids SAT Subcutaneous Abdominal Adipose Tissue SHS Senior High School University of Ghana http://ugspace.ug.edu.gh xix SPSS Statistical Package for Social Sciences SSA Sub-Saharan Africa TC Total Cholesterol TG Triglyceride UNAIDS United Nations Programme on HIV and AIDS VAT Visceral Abdominal Adipose Tissue VCT Voluntary Counselling and Testing WHF World Heart Federation WHO World Health Organization University of Ghana http://ugspace.ug.edu.gh xx OPERATIONAL DEFINITION OF TERMS Diabetes Diabetes is a chronic, metabolic disease characterized by elevated levels of blood glucose (or blood sugar), which leads over time to serious damage to the heart, blood vessels, eyes, kidneys and nerves. Fasting blood glucose (FPG) ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 hours, or a random plasma glucose ≥200 mg/dl (11.1 mmol/l) among those who have eaten within the last 8 hours. Hypertension Hypertension, also known as high or raised blood pressure, is a condition in which the blood vessels have a persistently raised pressure. Blood is carried from the heart to all parts of the body in the vessels. Each time the heart beats, it pumps blood into the vessels. Blood pressure is created by the force of blood pushing against the walls of blood vessels (arteries) as it is pumped by the heart. The higher the pressure, the harder the heart has to pump. Hypertension is a systolic pressure of 140 mm Hg or higher or a diastolic pressure of 90 mm Hg or higher. Dyslipidemia Dyslipidemia is defined as the total cholesterol, LDL, triglycerides, apo B or Lp (a) levels above the 90th percentile or HDL and apo A levels below the 10th percentile of the general population. will be defined as TC ≥5.2 mmol/l, HDL-C ≤ 1.03 mmol/l, TG ≥ 1.7 mmol/l or LDL-C ≥ 3.4 mmol/l according to National Cholesterol Education Program (NCEP) guidelines University of Ghana http://ugspace.ug.edu.gh xxi Diet Quality Individual dietary diversity score (IDDS) was be used as an indicator of Diet Quality. It is calculated by summing the number of unique food groups consumed during last 24 hour Cardiovascular disease Cardiovascular disease (CVD) is the name for the group of disorders of heart and blood vessels, and include: coronary heart disease (heart attack), cerebrovascular disease (stroke), peripheral vascular disease, heart failure, rheumatic heart disease, congenital heart disease, cardiomyopathies. Risk factors A risk factor is a variable associated with an increased chance of developing a disease or an infection. Common, preventable risk factors underlie most non-communicable diseases. Most non- communicable diseases are the result of four particular behaviours (tobacco use, physical inactivity, unhealthy diet, and the harmful use of alcohol) that lead to four key metabolic/physiological changes (raised blood pressure, overweight/obesity, raised blood glucose and raised cholesterol). HIV (human immunodeficiency virus) HIV (human immunodeficiency virus) is a virus that attacks cells that help the body fight infection, making a person more vulnerable to other infections and diseases. It is spread by contact with certain bodily fluids of a person with HIV, most commonly during unprotected sex (sex without a condom or HIV medicine to prevent or treat HIV), or through sharing injection drug equipment. ART Standard antiretroviral therapy (ART) consists of the combination of at least three antiretroviral (ARV) drugs to maximally suppress the HIV virus and stop the progression of HIV disease. Huge reductions have been seen in rates of death and suffering when use University of Ghana http://ugspace.ug.edu.gh xxii is made of a potent ARV regimen, particularly in early stages of the disease. University of Ghana http://ugspace.ug.edu.gh xxiii APPENDICES Figure 1. Conceptual framework suggesting plausible mechanisms by which ART, socio-cultural factors, HIV infection, and traditional risk factors may influence cardiovascular disease risk and quality of diet. 14 Figure 2: Schematic presentation of the thesis organization ....................................................................... 16 Fig. 3: Prevalence of HIV among adults aged 15 to 49, 2017, by WHO Regions ...................................... 19 Figure 5: Pooled prevalence of metabolic risk factors among ART naïve and ART patients .................... 49 Figure 6: Obesity prevalence forest plot for PLHIV on ART versus PLHIV but ART-naïve .................... 50 Figure 7: Diabetes prevalence forest plot for PLHIV on ART versus PLHIV but ART-naive .................. 51 Figure 8: Blood Pressure prevalence forest plot for PLHIV on ART versus PLHIV but ART-naïve ........ 51 Figure 9: High Triglyceride prevalence forest plot for PLHIV on ART versus PLHIV but ART-naive ... 52 Figure 10: Total Cholesterol prevalence forest plot for PLHIV on ART versus PLHIV but ART-naive .. 52 Figure 11: High LDL prevalence forest plot for PLHIV on ART versus PLHIV but ART-naive ............. 53 Figure 12: High HDL prevalence forest plot for PLHIV on ART versus PLHIV but ART-naïve ............. 54 Figure 13: Study setting .............................................................................................................................. 62 Figure 14: Consumption of different food groups in the previous 24 hours of the study .......................... 90 Figure 15: Prevalence of diabetes ............................................................................................................... 98 Figure 16: Prevalence of hypertension ...................................................................................................... 98 Figure 17: Prevalence of dyslipidemia ........................................................................................................ 99 Appendix 2: Information Sheet ................................................................................................................. 194 Appendix 3: Medical Report Form ............................................................................................................ 196 Appendix 4: Ghana Health Service Ethical Clearance Letter .................................................................... 197 Appendix 5: Letter of Introduction, St. Martins Hospital ......................................................................... 198 Appendix 6: Consent Form........................................................................................................................ 199 Appendix 7: Interpreter’s Statement ........................................................................................................ 200 Appendix 8: Investigator Statement and Signature .................................................................................. 201 Appendix 9: Statement of Witness ........................................................................................................... 202 Appendix 10: Questionnaire ..................................................................................................................... 203 University of Ghana http://ugspace.ug.edu.gh 1 CHAPTER ONE INTRODUCTION This chapter presents background context to the study, the problem statement, and objectives of the study. Further, questions that this research work aimed to address, the public health importance of the study as well as the conceptual framework, and organization of the entire thesis. 1.0 Background The effective rollout of antiretroviral therapy (ART) has given rise to an increased life expectancy of people living with HIV (PLHIV) (Ingrid T Katz & Maughan-Brown, 2017; McManus et al., 2012; Teeraananchai, Kerr, Amin, Ruxrungtham, & Law, 2017) . By 2019, there were about 38 million individuals living and aging with HIV and 1.7 million becoming infected every year (UNAIDS, 2019). Treatment with effective antiretroviral therapy (ART) has changed the course of disease and is key in the treatment of people infected with human immunodeficiency syndrome (HIV) (Ali et al., 2014; de Coninck et al., 2018; Günthard et al., 2016). The effectiveness of ART has led to a substantial decrease in death among people living with HIV (Deeks, 2009; Justice, 2010; C. A. Sabin, Mallon, & Winston, 2018; Stevens, 2017), leading to an increase in their life expectancy (de Coninck et al., 2018), which nevertheless remains lower than that of the general population (Collaboration, 2009; Lohse et al., 2007; May et al., 2011; Modrich et al., 2010). Public health and clinical issues related with aging have become more common in HIV-positive individuals (Smit et al., 2015), including increased risks for hypertension, diabetes, and dyslipidemia (Bouatou et al., 2018; Divala et al., 2016; Gueye et al., 2017; Hasse et al., 2011). University of Ghana http://ugspace.ug.edu.gh 2 Therefore, as patients infected with HIV are now living longer on ART, chronic health complications represent an increasingly important health issue, which is attributed to both HIV- related and traditional risk factors (Collaboration, 2008; Matthew S Freiberg et al., 2013; Ingrid T Katz & Maughan-Brown, 2017; Rotger et al., 2013; Teeraananchai et al., 2017). The rate of non-communicable illnesses proceeds to rise universally (Gowshall & Taylor- Robinson, 2018; Hunter & Reddy, 2013; Mensah G. A. & Mayosi, 2013; Nyirenda, 2016; Oni et al., 2014), where over 85% of NCD-related deaths are happening in low or middle-income countries (LMIC) (World Health Organization, 2014). Cardio-metabolic and pulmonary diseases, cancers, and mental health disorders are included in the most common NCDs in LMICs (Mayosi et al., 2009). Infections that are opportunistic in nature and acquired immune deficiency syndrome (AIDS) related cancers which characterized the pre-ART era have given way to challenges of non-communicable diseases (NCD) in persons living and aging with HIV (Hirschhorn, Kaaya, Garrity, Chopyak, & Fawzi, 2012; Magodoro, Esterhuizen, & Chivese, 2016). Non-communicable diseases are chronic diseases that constitute the largest cause of deaths in the world (Gowshall & Taylor-Robinson, 2018), with cardiovascular diseases (CVDs) in the lead (Al- Mawali, 2015). Cardiovascular diseases (CVDs) are the topmost cause of deaths worldwide resulting in 17.3 million deaths per year, projected to reach 23.6 million by 2030 (American Heart Association, 2015). The World Heart Federation mentioned that the number of deaths taking place in a year due to CVDs is 17.3 million (Hao et al., 2017). Diagnosis and treatment costs of CVDs were increasing at a higher rate and expected to escalate more in the next ten years (Pala, Anju, Dyavaiah, Busi, & Nauli, 2020). The financial burden related to CVDs is due to the increment within the chance variables of CVDs such as diabetics, obesity, and development of the geriatric populace (Iafisco, Alogna, Miragoli, & Catalucci, 2019). Current statistics indicate University of Ghana http://ugspace.ug.edu.gh 3 that cardiovascular diseases have been the single foremost cause of deaths globally (Pala et al., 2020). A study among 525 HIV patients found that, 9.7% (n=51) had hypertension and 15.6% (n=82) were reportedly patients with diabetes. With respect to the serum lipid profile, 24.8% and (n=130) had hypertriglyceridemia (Sanuade, Baatiema, Christian, & Puplampu, 2021). A survey on ‘psychosocial components and cardiovascular diseases’ examines the impact of psychosocial components on morbidity and mortality rate of CVDs. Negative enthusiastic states (depression, anger, anxiety, and hostility), social ties, social back, social strife, and unremitting and intense psychosocial stressors have associated with the expanded hazard of cardiovascular dismalness and mortality (Pala et al., 2020). Lifestyle choices, some health conditions, and ART are considered risk factors for CVD (Fryar, Herrick, Afful, & Ogden, 2016; Muyanja, Muzoora, Muyingo, Muyindike, & Siedner, 2016). Ideal cardiovascular health is defined by being a non-smoker, having a body mass index <25 kg/m2, meeting physical activity requirements, consuming a diet that adheres to the Dietary Guidelines, having a total cholesterol <200 mg/dL achieved without medication, a blood pressure <120/80 mmHg achieved without medication, and a fasting blood glucose <100 mg/dL (Lloyd-Jones et al., 2010). The odds for CVD increases in the presence of these risk factors along with HIV viral infection (Drozd et al., 2017) and ART (Marcus et al., 2016; Yoshimura, 2017). Cardiovascular disease has become an important cause of morbidity and mortality in HIV infected persons in industrialized countries (De Socio, Pucci, Baldelli, & Schillaci, 2017; Magodoro et al., 2016). The situation may even be more serious among developing countries. A systematic review conducted by Bloomfield et al. (2014) submits that in low and middle income countries, cardiovascular conditions such as coronary artery diseases, heart failure, and stroke, hypertension amongst others are common in the HIV-infected populace. Another study conducted in Zimbabwe University of Ghana http://ugspace.ug.edu.gh 4 also found that hypertension and type 2 diabetes which are major risk factors of cardiovascular diseases were common comorbidities among people living with HIV (PLHIV) (Magodoro et al., 2016). A systematic review found that over a third of PLHIV appearing at health facilities and/or receiving antiretroviral treatment (ART) had some kinds of cardiovascular disorders (Haregu, Oldenburg, Sestwe, Elliott, & Nanayakkara, 2012). This evidence points to some relationship that exists between ART and cardiovascular risk factors. Inevitable age-related changes, increasing exposure to ART toxicities, effects of continuing inflammation, continuous immune dysfunction, and long-term HIV viral infection are postulated to drive these cardiovascular risks among people living with HIV (Longenecker et al., 2013; Martínez, Larrousse, & Gatell, 2009; Pathai, Bajillan, Landay, & High, 2013). It has been long recognized that ART may lead to metabolic syndrome including atherogenic dyslipidaemia, abdominal obesity, endothelial dysfunction, insulin resistance, and inflammation (Loonam & Mullen, 2012). The increase in life expectancy among PLHIV has happened alongside the epidemiological transition that is associated with an increase in non-communicable diseases (Dimala, Atashili, Mbuagbaw, Wilfred, & Monekosso, 2016), which may have confounded the real effect of antiretroviral therapy on the development of cardiovascular risk factors. Nutrition transition in the last few decades especially among the developing countries has played a major role in the upward trend in non-communicable diseases especially CVDs. Nutrition transition is characterized by a major shift in dietary pattern toward sweetened and fatty foods that have high energy density. This is coupled with a reduced level of physical activity leading to changes in body composition and high risk of obesity (Bishwajit, 2015) and preventable non- communicable diseases (Oyewole & Atinmo, 2015). University of Ghana http://ugspace.ug.edu.gh 5 Nutrition transition is also explained as a change from lack of food, to a rising problem of accumulation and obesity (Adogu, Ubajaka, Emelumadu, & Alutu, 2015). This has coincided with a change in disease patterns connected with changes in behaviours, lifestyles, diets, physical inactivity, smoking and alcohol consumption (Adogu et al., 2015). Diet and nutrition are crucial in the management of PLHIV, especially in the case of metabolic alterations related to antiretroviral therapy (ART), which could be associated with cardiovascular diseases (CVD) (Silva et al., 2010). Nutrition is a foundation for good health and development and an important component of this is maintaining a strong immune function (Academy of Science of South Africa, 2007). Achieving fundamental nutritional recommendations is a paramount concern when treating HIV patients at every stage of the disease (World Health Organization 2003). Albeit under-nutrition is still an issue among infected persons, the use of antiretroviral therapy (ART) in the light of nutrition transition has not only prolonged their survival, but also elevated the prevalence of overweight and obesity (Amorosa et al., 2005; Audain, Carr, Dikmen, Zotor, & Ellahi, 2017; Hendricks, Willis, Houser, & Jones, 2006; Silva et al., 2010). Therefore, long-term complications, such as cardiovascular diseases (CVD) connecting to diet and obesity have become more important (Hendricks et al., 2006). Samaras et al. (2009) in their study among men with HIV-associated lipodystrophy Syndrome (HALS) presented that saturated fat consumption was positively related with percentage body fat. And a study in Brazil that assessed diet quality among PLHIV by A. Duran, L. Almeida, A. Segurado, and P. Jaime (2008) found that people who are overweight had lower Healthy Eating Index (poorer diet quality) and are also not likely to realize dietary goals for dairy products and grains. Omega 3 fatty acids are dietary components mainly found in fish, nuts, and vegetable oils that are known to lower the risk of CVD by reducing serum triglycerides and decreasing inflammation University of Ghana http://ugspace.ug.edu.gh 6 (Krauss et al., 2000; Mahan, Raymond, & Escott-Stump, 2013). Omega-3 fatty acids have antiarrhythmic effects, haemodynamics regulation through better endothelial function by helping the release of nitric oxide from endothelial cells (Massaro, Scoditti, Carluccio, & De Caterina, 2008), and arterial endothelial function which help explain potential mechanisms of their action (Kris-Etherton, Harris, Appel, & Nutrition, 2003). Omega 3 fatty acids also act partly to reduce hepatic production of very low-density lipoprotein and by boosting the degradation of fatty acids and quickening triglyceride removal from the plasma (Innes & Calder, 2018). Several population- based studies have revealed that eating boiled or baked fish, is strongly related to reduced heart rate and systemic vascular resistance and lower occurrence of ischemic heart disease and heart failure (Dariush Mozaffarian, Prineas, Stein, & Siscovick, 2006; von Bibra, Paulus, & St John Sutton, 2016). In order to determine the best mode to provide an all-inclusive care, a complete understanding of the multifaceted health needs of the population living with HIV is required (Kendall et al., 2014), and that should include their overall cardiovascular risk and dietary pattern. 1.1 Problem Statement The gains made against HIV such as, improved quality of life, reduction in HIV-related mortality and morbidity, and increased viral suppression are under threat, not from the HIV itself, but from non-communicable diseases (NCDs), especially cardiovascular diseases (CVDs) that develop due to exposure to antiretroviral therapy (ART) (World Health Organization, 2016). Long exposure to ART is found to be a major risk factor for CVDs (Islam, Wu, Jansson, & Wilson, 2012; Marcus et University of Ghana http://ugspace.ug.edu.gh 7 al., 2016; Zanetti, Mendes, et al., 2018). Hypertension, diabetes, and dyslipidemia are commonly associated with ART (Islam et al., 2012; World Health Organization, 2016). Treatment coverage has almost quadrupled within the span of ten years, from 6.4 million in 2009 to 25.4 million (UNAIDS, 2019), and by December of 2018, approximately 64% of PLHIV in Africa were accessing ART (WHO, 2018). The greatest increase in ART coverage has been in low and middle income countries (Joint United Natiions on HIV/AIDS, 2016) thereby bearing the brunt of the burden of these disease (Bloomfield et al., 2014; Mensah et al., 2015). In Ghana, the estimated number of people living with HIV by 2019 was 342,307 with an adult prevalence of 1.7% (Ghana AIDS COmmission, 2020). The picture regarding ART coverage in Ghana is not any different form other African countries. About 47 percent of PLHIV are on ART coverage by the end of 2019, projected to reach 100% by 2025 (Ghana AIDS COmmission, 2020; "UNAIDS Ghana Data," 2018), culminating in an increase in longevity among PLHIV in Ghana. Indeed, it is estimated that about 8,000 deaths were averted by ART (Ghana AIDS COmmission, 2020). However, the implementation and rollout of the ARTs has been accompanied with rising levels of non-communicable diseases among PLHIV, for which cardiovascular diseases stand out. HIV infection and ART are independently associated with a high risk of cardiovascular diseases (David G Dillon et al., 2013). Metabolic and body-fat irregularities are common among HIV-infected adults receiving ART, and there is indication that suggests that such people have an increased risk of cardiovascular conditions (Savvoulidis, Butler, & Kalogeropoulos, 2019). In the D.A.D. study, it was found that CVD is one of the most common causes of deaths (accounting for about 12 percent of total mortality) among people living with HIV (Smith et al., 2011). Several other studies University of Ghana http://ugspace.ug.edu.gh 8 also report those antiretroviral medications increase the risk of cardiovascular disease, and the plausible explanation for the relationship was pointed at an increase in plasma lipids. In addition to the role of ARTs in CVDs among PLHIV, Ghana as a country and for that matter the Eastern Region is not spared from the nutrition transition African countries are going through. There is a major shift in diet, characterized by high calories, high sodium, low fruits and vegetables, sedentary lifestyle, high alcohol consumption, and obesity. Luke, Cooper, Prewitt, Adeyemo, and Forrester (2001) found a major change in the Ghanaian dietary pattern, from whole grains, vegetables, and fiber-rich diet to diet characterized by high levels of fats, highly processed carbohydrates, and table sugar. The picture regarding the weight of PLHIV has also changed, from HIV-related weight loss especially during the pre-ART era to an increase in weight gain following the rollout of ART resulting in high levels of overweight and obesity among HIV patients, thereby increasing their CVD risk. In a study carried out among HIV population, about 30 percent were either overweight or obese (Klassen & Goff, 2013). Today, greater emphasis is placed on reducing diet-related comorbidities in PLHIV because healthy diets remain critical for healthy aging (Katunge, 2017; Maertens, 2011). In fact, PLHIV may be impacted disproportionately by poor diet quality compared to uninfected individuals (Crush, Drimie, Frayne, & Caesar, 2011; Dellar & Karim, 2015). The role of diet is key in the management of conditions such as dyslipidemia among people with higher risk. For instance, consumption of low cholesterol diet and fish increases plasma levels of omega-3 and omega-6 fatty acids (Capili & Anastasi, 2013). Attaining the basic nutritional needs is therefore an important requirement in successful management of PLHIV (Organization, 2003; Tang, Quick, Chung, & Wanke, 2015). University of Ghana http://ugspace.ug.edu.gh 9 There is however little information regarding the cardiovascular risk burden of HIV population receiving treatment in Ghana. Christian Obirikorang et al., (2016) investigated the prevalence of metabolic syndrome among HIV-infected patients receiving antiretroviral therapy at the St. Dominic Hospital, Akwatia. They found that participants on antiretroviral therapy (ART) were significantly associated with higher prevalence of metabolic syndrome compared to those without ART (P < 0.05). Their study however failed to investigate the prevalence of the various cardiovascular disease risk factors. The relationship between ART type and cardiovascular risk factors in Ghanaian setting was not determined. In addition, there is a lack of structured nutritional guide for PLHIV in Ghana, and little is known about their dietary behaviour and nutritional status. Also, no research to date has examined the degree to which the association between ART intake, dietary pattern, and CVD risk factors among PLHIV may interact (Raiten, D. J. et al., 2005). 1.2 Research Questions Given the research gap in relation to the risk of CVD among PLHIV, the study sought to provide answers to questions below: 1. What is the effect of ART on CVD risk factor (diabetes, hypertension, dyslipidemia, and obesity)? 2. What is the diet quality of the PLHIV? 3. What is the prevalence of diabetes, hypertension, and dyslipidemia among the PLHIV? 4. Are there any relationships between diet quality and CVD risk factors, (diabetes, hypertension, and dyslipidemia)? 5. What is the 10-year cardiovascular disease risk among the PLHIV? University of Ghana http://ugspace.ug.edu.gh 10 1.3 Objectives 1.3.1 General Objective The main objective of this study was to assess the Diet Quality and Cardiovascular Disease Risk Factors among PLHIV on Treatment 1.3.2 Specific Objectives The specific objectives were: 1. To conduct a systematic review on the effects of ART on cardiovascular disease risk factors among PLHIV in Low and Middle-Income Countries (LMIC) 2. To evaluate diet quality of the people living with HIV (PLHIV) 3. To determine the prevalence of cardiometabolic risk factors (diabetes, hypertension, dyslipidemia) among PLHIV 4. To examined the relationship between diet quality and CVD risk factors, including plasma glucose, blood pressure, lipid levels, and metabolic syndrome 5. To model and predict a 10-year cardiovascular heart disease risk among the PLHIV 1.4 Conceptual Framework This section discusses the possible causality pathways of the metabolic CVD risk factors and how they may lead to the CVDs. Figure 1 describes how socio-cultural factors may affect the traditional risk factors which eventually contribute to cardio-metabolic risk factors of CVD. It illustrates how HIV infection itself and ART modulate the cardio-metabolic risk factors of CVD. It further University of Ghana http://ugspace.ug.edu.gh 11 describes how socio-cultural and the traditional risk factors may result in individual dietary diversity score which also may eventually lead to the cardio-metabolic risk factors of CVD. This conceptual framework was adapted because it provides the possible pathophysiological pathways that could lead to cardiovascular diseases and diet quality. This advantage of this framework is that, it provides a clear link between exposure variables and the outcome variables. The disadvantage may be the fact that not all possible explanatory variables may be captured in the conceptual framework. 1.4.1 Description of Framework Components Treatment with ART either with PI-based or not, and diet quality (dietary pattern) may lead to an increase in the development of cardiovascular risk including diabetes, hypertension, and dyslipidaemia among PLHIV. However, various factors such as exercise, age, smoking, and gender may confound this association. Adjustment of these confounders is necessary to define clearly the associations of HIV related CVD risk (Diabetes, Hypertention, Dyslipidaemia) and treatment of HIV infection with ART and Diet Quality. Good nutrition is deemed one of the few bulwarks against AIDS-related diseases and early death (Lemke, 2005). Traditional risk factors such as smoking, alcohol, physical inactivity, and obesity have long been found to be associated with cardiovascular risk factors. Ahwal, Andrews, Roy, and Lakshmy (2019); (Gbadamosi & Tlou, 2020; Janakiraman et al., 2020; Nyberg et al., 2018) in their recent study, found that the occurrence of hypertension and dyslipidemia were higher among smokers compared to non-smokers. A new meta-analysis published in the British Medical Journal reveals that, in the context of cardiovascular disease (CVD), no safe level of smoking exists (Le Bras, 2018). Smoking increases oxidative stress leading to systemic inflammation that may ultimately University of Ghana http://ugspace.ug.edu.gh 12 result in the development of hypertension or dyslipidemia (Bissinger, Bhuyan, Qadri, & Lang, 2019; Cecile C. et al., 2017). Cessation of smoking is therefore suggested to reduce oxidative stress related inflammation (Cecile C. et al., 2017). High alcohol consumption was also found to be associated increased risk for hypertension and diabetes (Sechi, Colussi, Novello, Pezzutto, & Catena, 2016; Walther et al., 2017). Roerecke et al. (2018) in a systematic review concluded that any alcohol intake was related to elevation in the risk for hypertension among men, and in women, there was no risk increase for intake of 1 to 2 drinks per day but there is an increased risk for higher consumption levels. Consumption of alcohol 3 to 4 times per week was found to be associated with significant risk of developing diabetes (Holst, Becker, Jorgensen, Gronbaek, & Tolstrup, 2017). Physical inactivity was also a traditional risk factor of diabetes, hypertension, and dyslipidemia established by several research studies (Bohn et al., 2015; Jagannathan, Patel, Ali, & Narayan, 2019; Ward, White, & Druss, 2015). Exercise regimens are therefore crucial in a successful management of hypertension, diabetes, dyslipidemia, and for that matter, CVD. There is a significant reduction in HIV-related morbidities and mortalities, and people living with HIV now have an increased life expectancy (Teeraananchai et al., 2017), making HIV virtually a chronic disease. However, ART is associated with increased risk of non-communicable diseases (NCD) such as hypertension (CU Nduka, Saverio Stranges, AM Sarki, PK Kimani, & OA Uthman, 2016), diabetes (Nazik Elmalaika et al., 2017),dyslipidemia (Amberbir et al., 2018; Nazik Elmalaika et al., 2017), and CVDs (Lundgren, Mocroft, & Ryom, 2018; Muyanja et al., 2016). ART also may alter the appetite of PLHIV resulting in poor dietary choices that can increase their risk to diabetes, hypertension, and dyslipidemia. For instance, in one study, ART was associated University of Ghana http://ugspace.ug.edu.gh 13 with increased appetite among PLHIV (I. T. Katz et al., 2013) which may lead to overweight and obesity. HIV infection itself is found to be associated with hypertension, diabetes, and dyslipidemia through endothelial dysfunction, hyper-coagulation, and immune activation (Dau & Holodniy, 2008; Mogadam et al., 2020). HIV itself may also reduce appetite for food, making the infected indulge in unhealthy dietary practices. Finally, poor diet is one of the main risk factors for diabetes, hypertension, and dyslipidemia (Rodríguez-Monforte, Flores-Mateo, & Sánchez, 2015). Atkins et al. (2016) found in their research that adherence to a high-sugar (high in biscuits, puddings, chocolates, sweets, sweet spreads, breakfast cereals) diet was linked with CVD events, and therefore concluded that avoiding ‘high- sugar’ food components may decrease the risk of cardiovascular diseases. A study has revealed that although the energy intake may be the same, the diet of people living with HIV had an increased amount of fat, saturated fat, and cholesterol (Klassen & Goff, 2013). The increased fat intake may be as a result of the need for high-calorie diet resulting from high basal metabolic rate and the effects of the virus and medications on hunger or satiety control, in addition to alterations in taste perception and the poor nutritional support given to PLHIV. All of the risk factors discussed above therefore increase the cardiovascular risk of PLHIV through diabetes, hypertension, and dyslipidemia, which are the key risk factors. University of Ghana http://ugspace.ug.edu.gh 14 Figure 1. Conceptual framework suggesting plausible mechanisms by which ART, socio- cultural factors, HIV infection, and traditional risk factors may influence cardiovascular disease risk and quality of diet. Adapted from Stoner, Stoner, Young, and Fryer (2012) 1.5 Justification/Public health implication of the study The risk of cardiovascular diseases (CVD) among people living with HIV is predicted to increase, given that the increased access to antiretroviral therapy (ART) is linked with increased longevity. HIV-infected individuals are at high risk of CVD associated with aging like all others. In addition, most of the antiretroviral drugs frequently used in SSA are linked with hypertension, diabetes, and dyslipidemia (Cardoso et al., 2013; Chiluba, Nkandu, Daka, Chola, & Chongwe, 2017). This study seeks to estimate the prevalence of CVD risk factors (diabetes, hypertension, dyslipidemia), determine diet quality, and investigate any associations between diet quality, ART type, and CVD risk factors. Having data on the prevalence of these abnormalities (cardiovascular risk factors) among the HIV infected persons will help in planning public health interventions that are targeted at the PLHIV. University of Ghana http://ugspace.ug.edu.gh 15 The data on the relationship between ART type and CVD risk factors will specifically facilitate selection of effective ART primary treatment regimen with less cardiovascular risk and develop strategies in managing the CVD risk factors when they occur. This study will provide evidence to support and improve dietary recommendations and nutritional management of HIV-infected adults that are on ART, including dietary and lifestyle modifications. Knowledge about dietary intake patterns will help to identify areas for improvement regarding unhealthy dietary behavior (Ministry of Health, 2009). Findings of the research may be used to influence other national policies and programs made by government and or other stakeholders that will directly or indirectly restore, promote, and maintain health. 1.6 Organization of the Thesis Chapter One provides a background to CVD risk factors among PLHIV. It further describes the magnitude of the research problem and provides the objectives of the study, conceptual framework and research questions. Chapter Two provides literature review on CVD risk factors among PLHIV (HIV, ART, and the traditional risk factors) and a systematic review of studies on the effects of ART on the cardio- metabolic risk factors of CVDs. Chapter Three gives a brief explanation and characteristics of the study area, target population, the methods used and the study design. Chapter Four provides the analysis, results and their interpretations in line with the study objectives and the conceptual framework. University of Ghana http://ugspace.ug.edu.gh 16 Chapter Five discusses the study findings, whiles Chapter Six gives a conclusion to the study based on the study findings and recommendations. Implication for future research interventions as well as contribution to knowledge were also provided by the research (figure 2) Figure 2: Schematic presentation of the thesis organization University of Ghana http://ugspace.ug.edu.gh 17 CHAPTER TWO LITERATURE REVIEW 2.0 Introduction This study has two main outcome variables; cardiovascular risk factors and individual dietary diversity score (IDDS) [a proxy for diet quality measurement] among the PLHIV. The first part reviews the epidemiology of HIV and the burden of CVDs. The second part examines cardiovascular disease risk factors among PLHIV. The third part discusses dietary patterns and diet quality among the PLHIV. A systematic literature review and meta-analysis was done at the first section to determine the effects of ART on the cardio-metabolic risk factors of CVD among PLHIV. 2.1 HIV and CVDs 2.1.1 Epidemiology of HIV In 2019, there were 38 million people living with HIV (UNAIDS, 2020) out of which 36.2 million are adults. By the end of 2019, 25.4 million (67%) people were accessing antiretroviral therapy, up from 6.4 million in 2009 (UNAIDS, 2020). New HIV cases have been reduced by 40% from 1998. In 2019, around 1.7 million people were newly infected with HIV, compared to 2.8 million people in 1998 (UNAIDS, 2020). Since 2010, new HIV infections have declined by 23%, from 2.1 million to 1.7 million in 2019 (UNAIDS, 2020). University of Ghana http://ugspace.ug.edu.gh 18 AIDS-related deaths have been decreased by 60% since the peak in 2004. In 2019, around 690 000 individuals passed on from AIDS-related sicknesses around the world, compared to 1.7 million individuals in 2004 and 1.1 million individuals in 2010 (UNAIDS, 2020). In 2019, there were 38.0 million people living with HIV (UNAIDS, 2020). Out of which 36.2 million are adults. By the end of 2019, 25.4 million (67%) people were accessing antiretroviral therapy, up from 6.4 million in 2009 (UNAIDS, 2020). The rate of NCDs is high in sub-Saharan Africa (SSA). In 2016, NCDs accounted for 54.7% of all deaths in South Africa (Maluleke, 2018). Cerebrovascular disease and ischaemic heart disease were graded fourth and fifth for years of life lost in 2015 and diabetes was the second biggest killer after TB in 2016. Only 12% of the global population live in Sub-Saharan Africa (A. G. Vos et al., 2019), yet accounts for 71% of the global burden of HIV infection (Kharsany & Karim, 2016). Ten countries, mostly in southern and eastern Africa, viz. South Africa (25%), Nigeria (13%), Mozambique (6%), Uganda (6%), Tanzania (6%), Zambia (4%), Zimbabwe (6%), Kenya (6%), Malawi (4%) and Ethiopia (3%), account for almost 80% of all people living with HIV (Kharsany & Karim, 2016). University of Ghana http://ugspace.ug.edu.gh 19 Source: World Health Organization, 2018 Fig. 3: Prevalence of HIV among adults aged 15 to 49, 2017, by WHO Regions An estimated 0.8% [0.6-0.9%] of adults aged 15-49 years worldwide are living with HIV, though the problem of the epidemic continues to vary appreciably between regions. The WHO African region stays most severely affected, with almost 1 in every 25 adults (4.1%) living with HIV and accounting for nearly two-thirds of PLHIV worldwide (World Health Organization, 2019). 2.1.2 The burden of CVDs Cardiovascular disease (CVD) is the term that embraces diseases of the heart and blood vessels (Pranata et al., 2020). Cardiovascular diseases (which incorporate coronary heart infection and stroke) are the foremost non-communicable diseases universally, responsible for about 17.8 million deaths in 2017, particularly in low and middle-income nations (LMICs) where close to 80% of the total CVD burden occurs (Kaptoge et al., 2019). University of Ghana http://ugspace.ug.edu.gh 20 The general rate of CVD deaths in low and middle-income countries together is 28%, including more than 3 million deaths before the age of 60, of which the majority can be prevented (Arroyo- Quiroz et al., 2020; Nguyen, 2012). This leads to 7% reduction of gross domestic product (GDP) in these countries (Ruan et al., 2018) 2.2 HIV infection, ART, traditional risk factors, and cardio-metabolic risk factors 2.2.1 HIV infection and cardio-metabolic risk factors Chronic immune system activation and inflammation related to HIV infection also plays key roles in causing vascular damage and increasing one’s risk of CVD (Hileman & McComsey, 2019; Hunt, 2012; Soysal, Arik, Smith, Jackson, & Isik, 2020). Although HIV causes the depletion of CD4 lymphocytes among HIV-infected persons who are antiretroviral therapy-naïve, HIV also paradoxically results in chronic immune activation (Zanni, Schouten, Grinspoon, & Reiss, 2014). Patients with uncontrolled viremia have been found to have elevated levels of circulating immune and inflammatory markers including monocyte activation markers (Kaplan et al., 2012), pro- inflammatory cytokines (Baker et al., 2010), markers of arterial inflammation (Mangili et al., 2014), soluble cytokine receptors (Kaplan et al., 2012; Ross et al., 2008), chemokines (Kaplan et al., 2012), acute-phase proteins (Beltrán et al., 2014), soluble leukocyte adhesion markers (Baker et al., 2010; Ross et al., 2008), and fibrin degradation products (Baker et al., 2010; Kaplan et al., 2012). Immune alterations are known to contribute to atherosclerosis (Hansson & Hermansson, 2011); more specifically through immune cell subsets (e.g., intermediate monocytes, CD4+ T-helper 1 cells), inflammation, and T-cell activation (Ammirati et al., 2012; Rogacev et al., 2012; Tracy et al., 2013). Indeed, studies have found that HIV-infected patients who were ART-naïve had more University of Ghana http://ugspace.ug.edu.gh 21 advanced subclinical atherosclerosis (Oliviero et al., 2009), increased arterial inflammation (Subramanian et al., 2012), and greater monocyte and lymphocyte activation when compared with HIV-uninfected controls (Oliviero et al., 2009; Pereyra et al., 2012; Subramanian et al., 2012). 2.2.2 ART and cardio-metabolic risk factors Medications introduced in the mid-1990s transformed HIV treatment (Boccara, 2008; Hoffmann & Jaeger, 2001; Kramer, Lazzarotto, Sprinz, & Manfroi, 2009; Nehal & Muredach, 2005). These medications enhanced longevity and quality of life in persons with HIV by significantly dropping morbidity and mortality rates (Areri, Marshall, & Harvey, 2020). Progresses within the treatment of HIV/AIDS given colossal benefits to communities and governments through decrease of budgetary and society burdens, but these focal points appear to have come at a cost (Watson, 2015). Despite all the exceptional properties of antiretroviral solutions, some chronic conditions such as hyper-insulinemia, dyslipidemia, and disturbances in glucose homeostasis have been recorded as the direct antagonistic impacts of ART or as a result of combination with other risk factors such as HIV itself, an unhealthy way of life, and environmental variables (Bowman & Funderburg, 2019; Carr, Samaras, Burton, et al., 1998; Walli et al., 1998). The metabolic side effects of Art showing as chronic complications generally have multiple pathogenic mechani sms. However, ART is considered the foremost noteworthy contributing factor compared with other causal components such as maturing or an undesirable way of life (Bowman & Funderburg, 2019). It is not clear whether the units that have been clustered under the term “lipodystrophy syndrome” are different or interrelated components (Hejazi & Rajikan, 2015). Each single peculiarity within University of Ghana http://ugspace.ug.edu.gh 22 the serum lipid or glucose level can happen freely and exclusive of others, and the seriousness of the anomaly may vary from case to case (Hejazi & Rajikan, 2015). Of the six antiretroviral drug classes, the metabolic side effects of ART are most frequently detected with protease inhibitors (PIs), followed by Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs), and Non- nucleoside reverse transcriptase inhibitors (NNRTIs) that have different and specific effects (Ahmed, Woodward, & Mital, 2017; Husain & Ahmed, 2015). Generally, ARTs (including NNRTIs, NRTIs, Fusion inhibitors (FIs), CCR5 antagonists and integrase inhibitors) are less involved in metabolic disorders with the exception of efavirenz (NNRTI agents), which may have a role in the occurrence of dyslipidemia (Hejazi & Rajikan, 2015). 2.2.3 Traditional and cardio-metabolic risk factors 2.2.3.1 Smoking Cigarette smoking increases the occurrence of CVD in a dose-dependent way (Conen et al., 2011; Y. H. Lee et al., 2011; Tomiyama et al., 2010), with even occasional smoking increasing the risk of CVD (Witter et al., 2015). The association between CVD and smoking results from several mechanisms that interact to contribute to vascular injury, atherosclerosis, thrombosis and vascular dysfunction, although the exact mechanisms are mainly unknown (DiGiacomo, Jazayeri, Barua, Ambrose, & health, 2019; Witter et al., 2015). Long-term prospective studies have demonstrated the considerable mortality risk reduction related to smoking cessation (Sitas, Bradshaw, Egger, Jiang, & Peto, 2018). 2.2.3.2 Alcohol Gathering scientific evidence shows that light to moderate alcohol intake may significantly lessen the risk of CVD and all-cause mortality (Ronksley, Brien, Turner, Mukamal, & Ghali, 2011). University of Ghana http://ugspace.ug.edu.gh 23 In contrast, excessive alcohol intake is poisonous to both the heart and general health of an individual (Corrao, Rubbiati, Bagnardi, Zambon, & Poikolainen, 2000; Ronksley et al., 2011). In particular, binge drinking, even among otherwise low drinkers, raises cardiovascular events and deaths (Corrao et al., 2000; Ronksley et al., 2011). The American Heart Association guidelines caution individuals not to begin drinking in the event that they don't as of now drink alcohol because it isn't conceivable to anticipate in which individuals liquor abuse will get to be an issue (Lucas, Brown, Wassef, & Giles, 2005). 2.2.3.3 Obesity Obesity has been linked with CVD as well as its risk factors (Starrett, 2016). A study conducted over a 22-year period examined the trajectories of change in BMI and other CVD risk factors before a CVD diagnosis. It was found that high BMI and waist circumference are risk factors for developing CVD (Dhana et al., 2016; Renzaho, Halliday, & Nowson, 2011). In another study, data were collected from CVD free participants from the Framingham Heart Study between 2002 and 2005 (n=3,001). Subcutaneous abdominal adipose tissue (SAT) and visceral abdominal adipose tissue (VAT) can be a more precise measurement of waist circumference; they were used to identify if there was a correlation with metabolic risk factors such as fasting plasma glucose, high- density lipoprotein cholesterol, total cholesterol, and triglycerides (Fox et al., 2007). After controlling age, waist circumference and BMI were associated with SAT and VAT levels (Fox et al., 2007). Overweight as well as obese individuals have a noticeably higher prevalence of hypertension (HTN) compared with lean subjects (Alpert, Lavie, Agrawal, Kumar, & Kumar, 2016; Bastien, Poirier, Lemieux, & Despres, 2014; Ng et al., 2014), and obesity increases coronary heart disease (CHD) risk factors for example hypertension (Alpert et al., 2016). Certainly, overweight and obese University of Ghana http://ugspace.ug.edu.gh 24 individuals have noticeably abnormal CHD risk factors, including higher blood pressure (BP), glucose abnormalities, dyslipidemia, and increased inflammation, all of which increase the risk of CHD (Alpert et al., 2016; Lavie, De Schutter, & Milani, 2015). Indeed the prevalence of CVD is increased in the setting of obesity (Lavie et al., 2016). HIV infection used to be a wasting disease, especially during the pre-ART era. But since the rollout of ART, the dynamics have shifted, from weight loss and wasting among PLHIV to accumulation of body fat and weight gain. In a study of 1683 HIV patients, only 2% were underweight, 37% were overweight, and 9% were obese (Crum-Cianflone et al., 2010). Multivariate predictors of a higher body mass index (BMI) at diagnosis embraced more current year of HIV diagnosis, older age, African American race, and earlier HIV stage (all p<0.05) (Crum-Cianflone et al., 2010). Most of patients (62%) gained weight during HIV infection (Crum-Cianflone et al., 2010). Therefore, the high prevalence of obesity and overweight among PLHIV also increases their risks for developing cardiovascular diseases just as found in non-HIV populations (Alpert et al., 2016; Lavie et al., 2016). 2.2.3.4 Physical inactivity The American College of Cardiology (ACC) and the American Hearts Association (AHA) Lifestyle Management Guideline suggest that adults require at least 150 minutes every week of moderate-intensity aerobic activity or 75 minutes per week of vigorous aerobic activity, or a combination of the two, if possible, spread during the week (American Heart Association, 2019). In a prospective cohort analysis, female registered nurses 30-55 years old were followed for 8 years to inquire about physical activity and CVD events using questionnaires (n=72,488) (Manson et al., 2000). Physically active women were more likely to be non-smokers, leaner, had a lower University of Ghana http://ugspace.ug.edu.gh 25 prevalence of reported diabetes, hypertension, hypercholesterolemia, and alcohol (Manson et al., 2000). Even after controlling for age, smoking status, BMI, and other related factors, the total physical- activity score was inversely related to risk of CVD events when comparing quintile groups with increasing relative risks for physical activity, and the lowest quintile group (p=0.002) (Manson et al., 2000). Using multivariate analyses, CVD risk was decreased by 31 % when averaging 4.0 to 6.9 hours every week spent in moderate or vigorous activity as well as 37 % when averaging 7 hours per week compared to those who averaged less than 1 hour per week (p<0.001) (Manson et al., 2000). Walking was also shown to reduce coronary events. Those in the top two quintiles had significantly lower risk for a CVD event compared to those in the lowest quartile (Manson et al., 2000). In women, vigorous activity in addition to walking can reduce CVD events; however, this study did not investigate these risks for men. The Harvard Alumni Health Study investigated physical activity effect of CHD risk in men (n=12,516) (Sesso, Paffenbarger, & Lee, 2000). Quality and intensity of the physical activity were extracted from questionnaires provided from men with a mean age of 57.7 years old. Sesso et al. (2000) found that total activities and vigorous activities showed a relationship with the risk of CHD. Men who expended >8400 kJ per week participating in vigorous activities had a 10% to 20% decreased risk of CHD. Men who walked ≥5 km per week had a reduced risk of CHD by 13 % compared to those who did not (Sesso et al., 2000). Similar to women, an increase in physical activity proved a reduced rick for coronary related illnesses. University of Ghana http://ugspace.ug.edu.gh 26 Table 1: Lifestyle and cardio-metabolic risk factor analysis Risk factor Metric Optimum Low risk High risk Disease outcome Reference Alcohol use Standard drinks/day M: ≤1 F: ≤1 M: ≥3 F: ≥2 M: ≥5 F: ≥4 CVD; respiratory disease; cancers; diabetes; digestive disorders (O’Keefe, Bybee, & Lavie, 2007) Tobacco smoking Cigarettes/day 0 ≥1 ≥1 CVD; respiratory disease; cancers; diabetes; hypertension (Erhardt, 2009; Stoner et al., 2012) Poor diet Fruit and vegetable (servings/day) ≥5 < 5 < 1 CVD; cancers (Grimm et al., 2010; Saha et al., 2011) Overweight/ Obesity Waist: hip ratio1 M: ≤0.90 F: ≤0.80 M:≥0.92 F: ≥0.82e M: ≥0.98 F: ≥0.88 CVD; hypertension; diabetes; cancers (Huxley, Mendis, Zheleznyakov, Reddy, & Chan, 2010; Qiao & Nyamdorj, 2010) Physical inactivity Moderate physical activity (minutes/day) ≥30 days (5 days/ week) <30 days Sedentary CVD; cancers; diabetes; hypertension (Garber et al., 2011) CVD: Cardiovascular diseases; F: Female; M: Male 2.2.4 Cardio-metabolic Risk Factors Among PLHIV The demographics of a population, physical activity level, smoking, obesity, and alcohol consumption have all been related to CVD (Starrett, 2016). Healthy lifestyle choices of individuals can dictate health status later in life. Healthy lifestyles including, five or more servings of fruits and vegetables daily, consistent exercise, BMI 18.5-29.9 kg/m2, and smoking status led to a University of Ghana http://ugspace.ug.edu.gh 27 reduction in the risk of developing CVD and mortality (King, Mainous, & Geesey, 2007; Pallazola et al., 2019). 2.2.4.1 Cholesterol The two main blood lipids are triglycerides and cholesterol. These two blood lipid are borne on lipoproteins, the most vital of which are high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Both blood lipids carry cholesterol, but it is high LDL-cholesterol levels that have been shown to be pro-atherogenic (Defesche et al., 2017; Karalis, 2009; Teramoto et al., 2010), whereas low levels of HDL-cholesterol are related to increased CVD morbidity and mortality (A. A. Lucero et al., 2014; D. Lucero, Neufeld, & Remaley, 2018; Mohtavinejad, Nakhaee, Harati, Poodineh, & Afzali, 2015). Conversely, high HDL-cholesterol levels are related to reduced risk of CVDs (A. A. Lucero et al., 2014; D. Lucero et al., 2018; Mohtavinejad et al., 2015). In population studies, serum total cholesterol is regularly utilized as a surrogate for LDL-cholesterol levels; be that as it may, estimation of LDL-cholesterol concentrations confers more prominent predictive value for cardiovascular events (Teramoto et al., 2010). High cholesterol levels usually have no symptoms, and people may not know that they have the condition unless they did a blood test (Witter et al., 2015). Therefore, the best way to ascertain the true prevalence of high cholesterol in the community is through fasting blood samples (Marzetti et al., 2018). An LDL-cholesterol level <100 mg/dL is considered optimal (N. J. Stone, Bilek, & Rosenbaum, 2005). A survey done by the World Health Organization (WHO) found higher total cholesterol levels in urban (38%) than rural (35%), and an increased prevalence with age (30% among 18 to 35-year- olds vs. 44% for 50 to 65-year-olds) (World Health Organization, 2010). University of Ghana http://ugspace.ug.edu.gh 28 2.2.4.2 Hypertension Hypertension is a major risk factor for CVD (Witter et al., 2015). For every 20-mmHg increase in systolic or 10 mmHg increase in diastolic blood pressure, there is twice increase in deaths from both coronary heart disease (CHD) and stroke (Chobanian et al., 2003). Hypertension is linked with more years lived with CVD, shorter life expectancy free of CVD, and shorter overall life expectancy, (Franco, Peeters, Bonneux, & de Laet, 2005). 2.2.4.3 Diabetes Triant et al. (2007) found a higher prevalence of Type 2 diabetes mellitus among PLHIV, compared to those who were HIV-negative (11.5% versus 6.6%; P < 0.001). Brown et al. (2005) also found PLHIV to be about four times more likely to develop Type 2 diabetes, compared with persons without HIV. Antiretroviral therapy has been known as a key predictor of diabetes mellitus in PLHIV (Llabre et al., 2006); Larsson et al., 2006): about 10 percent of PLHIV on ART may present with diabetes mellitus (Calza et al., 2011; Kalra & Agrawal, 2013). HIV-infected persons also stand a chance of developing diabetes mellitus (Dagogo-Jack, 2008; Kalra et al., 2011). The clinical presentation of antiretroviral-associated diabetes mellitus is usually consistent with Type 2 diabetes (Dagogo- Jack, 2008; Kalra et al., 2011). However, some PLHIV may present with a form of Type 1 diabetes that is autoimmune-related resulting from an exaggerated immune response to ART treatment (Kalra et al., 2011; Takarabe et al., 2010). 2.2.5 Pathogenesis of CVDs among PLHIV Enhanced inflammatory response underlying the mechanism of early development of atherosclerosis in HIV disease could be attributed to direct viral effects, host immune response to infection, or be secondary to metabolic dysfunction by HAART use (Grinspoon & Carr, 2005; University of Ghana http://ugspace.ug.edu.gh 29 Marin-Palma, Castro, Cardona-Arias, Urcuqui-Inchima, & Hernandez, 2018; Saylor et al., 2016; Triant, Lee, Hadigan, & Grinspoon, 2007). Many studies have indicated that HIV-infected macrophages and reservoir could adversely affect vascular and myocardial function through systemic release of inflammatory cytokines that control the immune response, including tumor necrosis factors, interleukins, and interferon (Brothers et al., 2009). Higher level of these cytokines in ART naive patients indicates the role of HIV infection per se rather than that of ART induced