Weight gain during the dolutegravir transition in the African Cohort Study

Abstract

Introduction: Dolutegravir (DTG) has become a preferred component of first-line antiretroviral therapy (ART) in many settings but may be associated with excess weight gain. We evaluated changes in weight and body mass index (BMI) after switch to single-tablet tenofovir/lamivudine/dolutegravir (TLD) by people living with HIV (PLWH) in four African countries. Methods: The African Cohort Study (AFRICOS) prospectively follows adults with and without HIV in Kenya, Uganda, Tanzania and Nigeria. Demographics, ART regimen, weight, BMI and waist-to-hip ratio were collected every 6 months. Multivariable Cox proportional hazards modelling was used to estimate hazard ratios and 95% confidence intervals (CIs) for factors associated with developing a BMI ≥25 kg/m 2 . Linear mixed effects models with random effects were used to examine the average change in BMI, weight and waist-to-hip ratio. Results: From 23 January 2013 to 1 December 2020, 2950 PLWH were enrolled in AFRICOS and 1474 transitioned to TLD. In adjusted models, PLWH on TLD had 1.77 times the hazard of developing a high BMI (95% CI: 1.22-2.55) compared to PLWH on non-TLD ART. Examining change in weight among all PLWH on ART, participants on TLD gained an average of 0.68 kg (95% CI: 0.32-1.04) more than PLWH on other regimens after adjusting for duration on ART, sex, age, study site and CD4 nadir. Among participants who switched to TLD, the average change in weight prior to TLD switch was 0.35 kg/year (95% CI: 0.25-0.46) and average change in weight was 1.46 kg/year (95% CI: 1.18-1.75) in the year following transition to TLD after adjustment for confounders. Conclusions: Elevated BMI and weight gain among PLWH on TLD are concerning safety signals. Implications for the development of metabolic comorbidities should be monitored, particularly if annual weight gain persists during continued follow-up after transitioning to TLD.

Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir in adults living with HIV: evidence from routine care in Johannesburg, South Africa

“…More recently, out of the African Cohort Study (AFRICOS), which was also conducted in routine care settings, researchers found the average change in weight prior to switching to a dolutegravir-based regimen was 0.35 kg/year, which increased to an average change in weight of 1.46 kg/year in the year following transition to dolutegravir, corresponding to a 4-fold increase. 21 Our results provide support for these findings.…”

“… 23 In a multinational cohort of adults with well-controlled HIV, women on dolutegravir had a higher mean BMI and waist circumference than did women on an alternative ART regimen or men on dolutegravir. 21 , 22 Our results do not fully support this, as women in our cohort who switched to dolutegravir experienced similar weight gain as did men who switched to dolutegravir. This could be a result of a slightly higher uptake of dolutegravir in men compared to women in the full sample prior to matching.…”

“…Prior literature has also demonstrated potential differential effects of INSTIs on weight gain among men and women. 21 , 22 In the NAMSAL study, women were more likely to experience a ≥10% change in weight over 48-week follow-up period compared to men. 23 In a multinational cohort of adults with well-controlled HIV, women on dolutegravir had a higher mean BMI and waist circumference than did women on an alternative ART regimen or men on dolutegravir.…”

Non‐communicable diseases by age strata in people living with and without HIV in four African countries

“…INSTIs, particularly second‐generation INSTIs, have been implicated in substantial weight gain [ 24 , 25 , 26 ]. While over 70% of PLWH age ≥50 were on an INSTI at the most recent visit, DTG was not programmatically rolled out by PEPFAR until late 2018 [ 27 ].…”

Hypertension and human immunodeficiency virus: A paradigm for epithelial sodium channels?

“…Sax et al further showed that demographic factors associated with weight gain included lower CD4 cell count, higher HIV type 1 RNA, no injection drug use, female sex, and black race. Several observational studies have also indicated significant weight gain in PWH on INSTIs with some indicating a predisposition toward black race and female sex ( 72 , 156 , 157 ). Excessive weight gain, particularly central obesity is associated with vascular endothelial dysfunction.…”