Prevalence of overweight and obesity among adolescents living with HIV after dolutegravir - based antiretroviral therapy start in Kampala, Uganda.

BACKGROUND: Dolutegravir (DTG)-based antiretroviral therapy (ART) is currently the preferred first-line treatment for persons living with HIV (PLHIV) including children and adolescents in many low- and middle-income countries including Uganda. However, there are concerns about excessive weight gain associated with DTG especially in adults. There remains paucity of current information on weight-related outcomes among adolescents on DTG. We determined the prevalence of excessive weight gain and associated factors among adolescents living with HIV (ALHIV) receiving DTG-based ART in Kampala, Uganda. METHODS: Cross-sectional study involving ALHIV aged 10-19 years on DTG-based ART for at least one year were recruited from public health facilities in Kampala between February and May 2022. Excessive weight gain was defined as becoming overweight or obese per body mass index (BMI) norms while on DTG-based ART for at least one year. Demographic, clinical and laboratory data were collected using interviewer-administered questionnaires and data extracted from medical records. At enrolment, blood pressure and anthropometry were measured and blood was drawn for blood glucose and lipid profile. Data was summarised using descriptive statistics and logistic regression was performed to determine the associated factors. RESULTS: We enrolled 165 ALHIV with a median age of 14 years (IQR 12-16). Eighty (48.5%) were female. The median duration on ART and DTG was 8 years (IQR 7-11) and 2 years (IQR 1-3) respectively. At DTG initiation, the majority of participants (152/165, 92.1%) were ART-experienced, and had normal BMI (160/165, 97%). Overall, 12/165 (7.3%) adolescents (95% CI: 4.2-12.4) had excessive weight gain. No factors were significantly associated with excessive weight gain after DTG start in ALHIV. However, all ALHIV with excessive weight gain were females. CONCLUSION: Our study found a prevalence of 7.3% of overweight and obesity in ALHIV after initiating DTG. We did not find any factor significantly associated with excessive weight gain in ALHIV on DTG. Nonetheless, we recommend ongoing routine monitoring of anthropometry and metabolic markers in ALHIV as DTG use increases globally, to determine the exact magnitude of excessive weight gain and to identify those at risk of becoming overweight or obese while taking the medication.

Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults.

BACKGROUND: The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance. METHODS: In this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%ß respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance. RESULTS: Of the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28-37). Despite a trend towards an initial increase in both HOMA IR and HOMA%ß at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%ß at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: -0.46, 0.733, p = 0.648) and (difference in mean HOMA %ß from baseline: 6.7, 95%CI: -13.4, 26.8, p = 0.506) respectively. CONCLUSION: We demonstrated insignificant changes in both insulin resistance and pancreatic beta cell function in clinically stable young adult Ugandan PWH on dolutegravir for 48 weeks. We add to the body of evidence demonstrating glucose metabolic safety of dolutegravir in ART naïve patients. Ugandan guidelines should reconsider restricting DTG initiation in ART naive adults at high risk for diabetes.