TAF and Integrase Inhibitors shown to promote weight gain in people living with HIV

Tenofovir alafenamide (TAF) promotes weight gain in people who switch HIV treatment regimen according to results from three studies presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2021).

The largest study on weight gain so far included a cohort of 14,703 people on antiretroviral treatment (ART) in Europe and Australia. 80% of participants were already receiving ART at the start of the study. The observation lasted more than two years, at the end of which researchers analysed the association between weight gain with each drug – comparing the incidence of weight gain, measured by an increase in body mass index (BMI) of 7% or more, compared with lamivudine (3TC).

54% of the participants gained 7% or more of their BMI, with four antiretroviral drugs been associated with the weight gain:

• Integrase inhibitors, dolutegravir and raltegravir
• Nucleotide reverse transcriptase inhibitor (NRTI), TAF
• Non-nucleoside reverse transcriptase inhibitor (NNRTI), etravirine.

However, the likelihood of weight gain was higher when dolutegravir and TAF were used together. Taking each drug separately also increased the chances of gaining weight by an average of 30%.

In another study, researchers analysed data from 2,272 patients receiving care in major clinics in the United States and London. All participants had suppressed viral loads and switched to a new ART regimen with integrase inhibitors (INI). Of these, 47% had switched from tenofovir disoproxil fumarate (TDF) to TAF.

One year after changing ART, participants gained an average of 1.3 kg. Those who took dolutegravir gained 10% or more in weight. Also, a similar increase was found to be more likely in women; people with low or normal weight at baseline; people who switched from a previous regimen without integrase inhibitors; and those who changed from TDF to TAF.

Thirdly, an outpatient study covering eight centres in the United States analysed data from 736 people who switched to an integrase inhibitor, TAF, or both. Roughly 20% were women, 26% were black, and the average age was 51. The observation period lasted for two and a half years.

Those who switched to a regimen containing both INI and TAF gained the most weight. The researchers estimated that 87% of the weight gain in the first eight months was associated with an integrase inhibitor in the regimen in those also receiving TAF.

Each of these three studies suggest that TAF-based regimens promote weight gain in people switching from another ART regimen. However, the data on the role of integrase inhibitors are contradictory and requires further research.