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What are the roles of TAF and integrase inhibitors in weight gain?

Tenofovir alafenamide (TAF) was linked to weight gain in three large studies of people changing HIV treatment presented at CROI 2021. Each study identified TAF as a contributor to weight gain but produced conflicting findings on the role of integrase inhibitors.

TAF in combination with emtricitabine is included in several of the more commonly prescribed antiretroviral combinations and it has emerged in several studies as an independent risk factor for weight gain.

The three studies presented at CROI 2021 looked at people who changed treatment, not people just starting treatment, so any ‘return to health’ effect of starting treatment can be ruled out.

An analysis from the RESPOND cohort study covered 14,703 people in Europe and Australia.

Participants were followed for a median of 2.6 years and just over half of participants (54%) experienced a weight gain of at least 7% of body mass index (BMI). Four antiretroviral drugs were associated with an increased odds of weight gain in multivariate analysis: the integrase inhibitors dolutegravir and raltegravir, the non-nucleoside reverse transcriptase inhibitor etravirine, and TAF, a nucleotide reverse transcriptase inhibitor.

The odds of weight gain associated with dolutegravir and TAF were higher when the two drugs were used together, but both dolutegravir and TAF were independently associated with higher odds of weight gain of at least 30% of BMI.

To investigate how prior tenofovir use, or a switch from TDF to TAF, affected weight gain in people taking an integrase inhibitor, Professor Grace McComsey and colleagues looked at 2272 people receiving HIV care at major clinics in the US and London.

All participants were virologically suppressed and switched to a new integrase inhibitor regimen, including 64% who had previously been on a different integrase inhibitor. Forty-seven per cent switched from TDF to TAF at the same time. Participants gained an average of 1.3kg in the year following the switch, with no difference in mean weight gain between integrase inhibitors.

Weight gain of at least 10% was more likely in women, people underweight or normal weight at baseline, those switching from a prior non-integrase regimen and those switching from TDF to TAF.

An analysis of the US HIV Outpatients Study found that switching to an integrase inhibitor was independently associated with weight gain and that the greatest weight gain occurred in the first eight months after switching. Thereafter, further weight gain was largely attributable to TAF use.