Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium. Lancet HIV
Bansi-Matharu et al. on behalf of the RESPOND cohort consortium aimed to investigate factors associated with weight gain among people in the RESPOND cohort, focusing particularly on contemporary antiretrovirals, such as dolutegravir and tenofovir alafenamide.
People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral body-mass index (BMI) levels (baseline) were considered at each BMI measurement during antiretroviral treatment. They used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. They adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline.
14’703 people were included in this study, of whom 7’863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17–1·38), raltegravir (1·37, 1·20–1·56), and tenofovir alafenamide (1·38, 1·22–1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91–2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47–1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96–0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19–1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15–1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52–2·11, and 1·70, 1·44–2·01, respectively).
In conclusion, this study identified a significant and consistent association between exposure to dolutegravir, tenofovir alafenamide, and raltegravir and BMI increase and shows that both tenofovir alafenamide and dolutegravir are independently associated with a BMI increase (and the magnitude of the association is greater for both drugs when used concomitantly). This finding held true for several subpopulations, including participants with low BMI before treatment, ART-naïve participants, and those with high CD4 cell counts. Weight gain is associated with potential consequences, such as insulin resistance, dyslipidaemia, and hypertension. These consequences can in turn result in an increased risk of cardiovascular disease. When making the decision to start new antiretroviral treatment, clinicians and people with HIV should be aware of the potential weight gain associated with dolutegravir and tenofovir alafenamide, particularly in the first 3 years, and of the more extreme weight gain seen in a subset of people beyond 3 years. The accumulation of weight gain over time and the effect on weight once dolutegravir and tenofovir alafenamide are discontinued need to be investigated further.