Background
The impact of antiretrovirals on body weight in people with HIV is unclear. Reversible weight-suppressive effects of emtricitabine/tenofovir disoproxil fumarate (F/TDF) have been demonstrated, while effects of emtricitabine/tenofovir alafenamide (F/TAF) are debated. Comparison of F/TAF with placebo in people without HIV may give valuable insight into F/TAF’s effect on weight. We used data from pre-exposure prophylaxis efficacy studies to compare weight gain with F/TAF vs placebo among people without HIV.
Methods
Data from 2 randomized clinical trials were used: iPrEx (NCT00458393; F/TDF vs placebo; N=2499) and DISCOVER (NCT02842086; F/TAF vs F/TDF; N=3573). Weight was measured during regular study visits. The common F/TDF groups were used to bridge studies and compare mean weight change on F/TAF to placebo. Participants from countries not represented in the iPrEx placebo sample were excluded from this analysis (European sites from DISCOVER). Sensitivity analyses were limited to participants from North America and DISCOVER participants who used F/TDF at baseline (BL).
Results
DISCOVER participants were older, more likely of White race, had higher body mass index at BL, and more frequently used medication associated with weight change vs iPrEx participants. After adjusting for differences in demographics across trials, estimated mean weight change with F/TDF was similar between studies (Figure). Weight change from BL in participants on F/TAF with no prior F/TDF use (n=1422) was similar to placebo (Figure); there were no statistically significant differences in mean (95% CI) weight change at Week (W) 48 (+0.44 [-0.04, 0.92] kg) and W96 (+0.53 [-0.28, 1.34] kg). Among DISCOVER participants who switched from F/TDF to F/TAF (n=360), differences in mean weight change vs placebo were larger: +1.15 (0.53, 1.77) kg at W48 and +1.74 (0.78, 2.70) kg at W96. Results were consistent when restricted to North American participants and when using different model and sample weighting approaches.
Conclusions
This is the first analysis comparing changes in weight with F/TAF vs placebo. The observed weight trajectories in the 2 study samples with F/TDF were nearly overlapping, supporting the general validity of our cross-trial comparison. Greater weight gain among those who switched from F/TDF was consistent with a reversible weight-suppressive effect of F/TDF. Similar observed weight change with F/TAF and placebo in people without HIV suggests no clinically meaningful effect of F/TAF on weight gain.
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