If there’s any sanity to find in a mad, mad world, it’s that new HIV clinical research findings still flow forth as copiously as they were a year ago. For instance, we continue to gain precision in our understanding of the metabolic effects of some newer antiretrovirals, particularly tenofovir alafenamide (TAF) and dolutegravir (Tivicay, DTG). AIDS 2020 brought a few noteworthy developments in this area.
An analysis of the OPERA study, in which virally suppressed treatment-experienced people were switched from a regimen containing tenofovir disoproxil fumarate (TDF, Viread) to a TAF-containing regimen, found a marked early increase in weight gain among TAF recipients that plateaued over time.
Among participants whose only regimen change was to swap TDF for TAF, weight gain averaged 2.6 kg/year in the first nine months after switching, and 0.3 kg/year afterward.
Interestingly, participants whose background regimen included a boosted protease inhibitor appeared to experience slightly less weight gain (2.0 kg/year in the first nine months, and weight loss of 0.1 kg/year after) than those on an integrase inhibitor (2.6 kg/year initially, 0.3 kg/year after) or NNRTI (2.3 kg/year initially, 0.2 kg/year after).
Meanwhile, metabolic data from the TANGO study suggested that if a provider wanted to switch their patient off TAF due to metabolic concerns, they may want to be careful about what to switch to. In TANGO, which switched people from a stable TAF-based regimen to dolutegravir/lamivudine (we’ll have more on that two-drug regimen shortly), switching to the two-drug regimen tended to yield minor but statistically significant improvements in total cholesterol, LDL cholesterol, triglycerides, fasting insulin, and insulin resistance, but had no real impact on weight.
This association between the integrase inhibitor dolutegravir and weight gain also played out in data from the AFRICOS study, which examined body mass index (BMI) and hyperglycemia in the context of the rollout of dolutegravir/lamivudine/TDF in several African countries. The study found that people receiving the regimen were 85% more likely to become overweight (i.e., have a BMI of 25 kg/m2 or higher) and experienced higher incidence of hyperglycemia than people taking other antiretroviral regimens.
Long-term findings from the ADVANCE study, a first-line treatment trial in South Africa, suggest that the weight-increasing effects of dolutegravir and TAF may be particularly noticeable among women. Through 144 weeks, the study found markedly greater weight gain among women who received dolutegravir/lamivudine/TAF (12.3 kg on average) compared to women who received dolutegravir/lamivudine/TDF (7.4 kg) or efavirenz/lamivudine/TDF (5.5 kg). (That said, all three regimens were highly effective.)
All of this appears to be taking place within a broader trend of unhealthy weight gain among people living with HIV generally. A Kaiser Permanente study found that, over a 12-year span, BMI among people with HIV increased at a rate of 0.22 kg/m2 per year, compared to an increase of 0.06 kg/m2 per year for their HIV-negative counterparts—and that BMI increases were greater for people with HIV across baseline weight classifications, be they underweight, obese, or anything in between. We explore these data more deeply in a separate article.