Is tenofovir disoproxil fumarate associated with weight loss?

Recent clinical trials have shown weight gain associated with newer antiretrovirals. It is unclear how the nucleoside reverse transcriptase inhibitor backbone affects weight. Recent evidence suggests greater weight gain with tenofovir alafenamide (TAF) compared with tenofovir disoproxil fumarate (TDF). However, it is not fully understood whether TDF contributes to weight suppression.

A systematic search of PubMed, Embase and clinicaltrials.gov was conducted to identify all randomized control trials comparing TDF/FTC or TDF to control in HIV-negative individuals. The primary endpoint included the number of events of 5% weight loss. Mantel-Haenszel test with random-effects modelling was used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI). Further analyses of gastrointestinal (GI) adverse events were also undertaken.

Seven PrEP trials: PARTNERS, VOICE, TDF-2, Bangkok PrEP, iPrEX, FEM-PrEP and HPTN 084 were included in the analysis of weight loss, with a total sample size of 19 359. One study (HPTN 084) compared TDF/FTC to cabotegravir (CAB). HIV-negative individuals taking TDF were more likely to experience weight loss compared with control [odds ratio (OR) 1.44; 95% CI 1.12-1.85; P = 0.005). Exposure to TDF was also linked to greater odds of vomiting (OR 1.81; 95% CI 1.20-2.73; P < 0.005). There were no increased odds of nausea, diarrhoea or loss of appetite.

There is evidence in HIV-negative individuals that TDF may be associated with weight loss. Further research should be carried out in HIV-positive individuals, and clinical trials of TDF/FTC should publish weight data to widen the evidence base.