Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials

Abstract

Background Initiation of antiretroviral therapy (ART) often leads to weight gain. While some of this weight gain may be an appropriate return-to-health effect, excessive increases in weight may lead to obesity. We sought to explore factors associated with weight gain in several randomized comparative clinical trials of ART initiation. Methods We performed a pooled analysis of weight gain in 8 randomized controlled clinical trials of treatment-naive people living with human immunodeficiency virus (HIV) initiating ART between 2003 and 2015, comprising >5000 participants and 10 000 person-years of follow-up. We used multivariate modeling to explore relationships between demographic factors, HIV disease characteristics, and ART components and weight change following ART initiation. Results Weight gain was greater in more recent trials and with the use of newer ART regimens. Pooled analysis revealed baseline demographic factors associated with weight gain including lower CD4 cell count, higher HIV type 1 RNA, no injection drug use, female sex, and black race. Integrase strand transfer inhibitor use was associated with more weight gain than were protease inhibitors or nonnucleoside reverse transcriptase inhibitors (NNRTIs), with dolutegravir and bictegravir associated with more weight gain than elvitegravir/cobicistat. Among the NNRTIs, rilpivirine was associated with more weight gain than efavirenz. Among nucleoside/nucleotide reverse transcriptase inhibitors, tenofovir alafenamide was associated with more weight gain than tenofovir disoproxil fumarate, abacavir, or zidovudine. Conclusions Weight gain is ubiquitous in clinical trials of ART initiation and is multifactorial in nature, with demographic factors, HIV-related factors, and the composition of ART regimens as contributors. The mechanisms by which certain ART agents differentially contribute to weight gain are unknown.

Weight gain among treatment‐naïve persons with HIV starting integrase inhibitors compared to non‐nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada

“…The use of TAF, approved in the US in November 2015, is rapidly increasing given the lower incidence of adverse bone and renal effects compared to TDF. Recent data from pooled clinical trials and other studies indicate that TAF use predisposes to weight gain independent of concomitant INSTI use [20,30,31]. The very low number of participants receiving TAF is both a strength and a limitation of our study.…”

“…hormonal and psychotropic drugs) nor did we adjust for pregnancy, as these data were not routinely collected in the cohort. Furthermore, only 13% of participants were females; therefore, we might be misrepresenting the population‐level impact of weight gain in the target population of HIV positive individuals initiating ART in the United States and Canada during this period – especially as several studies have shown ART‐associated weight gain to be a greater problem among females [20,30]. Finally, we did not assess clinical outcomes, such as metabolic or cardiovascular disease incidence or progression, and future studies will be needed to determine the impact of the observed weight changes on the health of PWH.…”

The potential role of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) single‐tablet regimen in the expanding spectrum of fixed‐dose combination therapy for HIV

“…DTG and BIC appear to be associated with greater weight gain in ART‐naive patients than other INSTIs, as TAF is with other NRTIs . Preliminary data suggests this might be true in switch as well.…”

Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase

“…4 Secondly, greater weight gain was observed in patients treated with DTG compared to efavirenz (EFV) in two clinical trials in sub-Saharan Africa, and elsewhere, leading to concerns about long-term effects of obesity with lifelong ART. [5][6][7][8][9] Whilst cost-effectiveness analyses continue to support the use of DTG as rst-line therapy despite these issues, 10 the WHO and others are revisiting targeted use of efavirenz (EFV). Concerns remain about the use of EFV with widespread NNRTI resistance, which exceeds 10-15% in much of sub-Saharan Africa.…”