Effect of Dolutegravir-Based Regimen on Metabolic Syndrome among People Living with HIV in the Greater Accra Region

Abstract

Introduction: Globally, the expansion of antiretroviral therapy (ART) coverage has improved survival among people living with HIV (PLHIV) and has also reduced AIDS-related mortality in low-resource settings, including Ghana. However, as PLHIV live longer, they are exposed to environmental and behavioural risk factors in addition to HIV and ART which may increase their risk of metabolic disorders and cardiovascular diseases. A cluster of three or more of these metabolic disorders (elevated blood pressure, abnormal cholesterol level, elevated blood sugar, insulin resistance and abdominal obesity) is known as Metabolic Syndrome (MetS). Dolutegravir based regimen which is the current ART being used for HIV treatment has been shown to cause a significant weight gain (major risk factor for cardiometabolic conditions). Thus, the need to assess the effect of this drug combination on MetS. This study assessed the effect of dolutegravir-based regimen on the incidence of MetS and estimated the risk of Cardiovascular disease (CVD). It also assessed the challenges and level of adherence to the baseline requirements before ART initiation and routine checks. Method: A prospective cohort study was conducted among HIV-positive patients from Tema General Hospital HIV clinic. A sample size of 300 was estimated using command stpower cox in STATA version 14 (150 per cohort – those switching and those starting on the dolutegravir-based regimen) for the cohort study. These 300 participants were sampled from 588 participants who consented and were screened for eligibility to participate in the study using systematic sampling. The cohort was followed for 12 months and data was collected at baseline, 6 months and 12 months. MetS which was the primary outcome of measure was defined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria (i.e. having ≥3 of the following characteristics: elevated fasting blood glucose, elevated waist circumference, low high density lipoprotein cholesterol (HDL-C), elevated triglycerides and elevated blood pressure). Evaluation included laboratory data that were obtained after 8 hours overnight fast and a survey using a questionnaire totassess traditional risk factors associated with metabolic syndrome, HIV/ART-related factors and comorbidities. Prevalence was calculated as the number of cases divided by the total screened population. Incidence rate was calculated as the number of incident cases divided by the total person-months at risk. Cox proportional hazard model was used to estimate the hazard of MetS. The cardiovascular risk score assessment tools (5-year D:A:D CVD risk score, 10-year Framingham risk score and 10-year WHO/ISH risk prediction chart) were used to estimate the risk level of CVD among the study participants. In-depth interviews were conducted among newly diagnosed HIV-positive patients and heads in 10 of the 41 comprehensive HIV care clinics in the Greater Accra Region to ascertain some of the challenges they are encountering in adhering to the new ART guidelines. A sample of 50 patient’s folders were reviewed to abstract data on the tests, physical examination and information on medical and social history collected at baseline before ART initiation and routinely during the course of treatment to assess the facilities adherence to the ART guidelines. Results: Among the 588 participants that were screened, the mean age was 40.61 + 10.73years with 411 (69.9%) being females. The prevalence of MetS was 46.8% using the NCEP-ATPIII definition for MetS. Of the 300 sampled participants (150 per each cohort) followed up for 12 months, those who switched to dolutegravir-based regimen cohort were older in mean age (43.50+9.48) than those who had been newly diagnosed with HIV and were initiated on dolutegravir-based regimen [37.80+10.89]. Using the NCEP-ATPIII diagnostic criteria, the incidence rate of MetS per 100 person-months on dolutegravir-based regimen was 3.47 (CI:2.89 4.17) with incidence of 115 (38.3%). Among the metabolic subcomponents, 100 people had increased waist circumference, representing the component with the highest incidence at an incidence rate of 3.31 (CI: 2.72 – 4.02) per 100 person-months. Seventy-three (73) participants had elevated blood pressure, representing the component with the lowest incidence at an incidence rate of 3.54 (CI: 2.82 – 4.46) per 100 person-months. Dolutegravir-based regimen was found to be a significant risk factor in the development of MetS among the two cohorts even though those who had being on other drug regimen before the dolutegravir had 2.0 hazard of developing MetS compared to those who started with it. Use of dolutegravir-based regimen [HR=2.0; 95% CI (1.12, 3.55)], age groups [HR=58.4; 95% CI (4.27, 80.0)], sex [HR=0.38; 95% CI (0.16, 0.87)], employment status [HR=0.01; 95% CI (0.00, 0.13)], marital status [HR=8.31; 95% CI (2.22, 31.0)], number of adults in household [HR=3.45; 95% CI (1.20, 9.95)], WHO Stage [HR=17.9; 95% CI (1.45, 71.0)], family history of hypertension [HR=19.9; 95% CI (5.22, 75.9)], platelets counts [HR=1.01; 95% CI (1.01, 1.02)], creatinine levels [HR=9.32; 95% CI (1.65, 52.6)], HDL C [HR=2.11; 95% CI (1.29, 3.45)], triglyceride levels [HR=3.23; 95% CI (1.78, 5.88)], fasting blood glucose [HR=10.98; 95% CI (2.73, 44.16)], waist circumference [HR=5.13; 95% CI (1.76, 14.9)], body mass index [HR=11.2; 95% CI (4.13, 30.6)] and blood pressure [HR=2.05; 95% CI (1.08, 3.92)] were found to be significant risk factors for MetS. Majority of the participants were at low risk of developing CVD in the next 10 years using the 10-year FRS (65.7%) and the 10 year WHO/ISH prediction risk scores (76.3%). Using the D:A:D 5-year score, 56.2% of the participants were at moderate to high risk of developing CVD in 5 years. In terms of adherence to the ART guidelines, majority of the facilities surveyed (90%) were not adhering to it with inadequate staff and logistics being a major challenge they are encountering thus the non adherence. Conclusion: The incidence of metabolic syndrome was high among HIV-infected persons on dolutegravir-based regimen irrespective of whether they started with it or switched from one medication to it. The traditional risk factors also played a more significant role in its development. Therefore, there is a need for routine screening for MetS subcomponents throughout the course of ART (dolutegravir-based regimen) in Ghana and Sub-Saharan Africa as a whole.