Antiretroviral therapy (ART) containing integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF) has been associated with greater weight gain. Yet few studies have delineated between exposure to 'anchor' drugs [protease inhibitors (PI), nonnucleoside reverse transcriptase inhibitors (NNRTI) or INSTIs] and exposure to nucleoside reverse transcriptase inhibitors (NRTIs).

In this cohort of antiretroviral drug-naive patients who initiated ART from 2008-2022, we analyzed BMI gain for eight contemporary 'anchor' drugs and three contemporary NRTIs during the first 3 years of ART. We censored patients if they stopped, switched, or added another antiretroviral drug to their regimen.

We used generalized estimating equations (GEE) to assess the association between BMI gain and choice of ART and a nonlinear mixed model for the marginal coefficients of determination. We adjusted for time, baseline demographic and HIV-characteristics, and time-updated HIV and substance use-related variables.

The median BMI gain in 4 194 patients over 3 years was + 1.9 kg/m 2 [interquartile range (IQR) 0.1-4.1]. Most patients were black (55%) and men (77%). Multivariable modeling from 20 528 BMI measurements revealed that the type of ART accounted for just 9% of the predicted BMI change. Only efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) were independently associated with (lower) weight gain but no differences were observed between INSTIs, PIs, and rilpivirine, or between TAF and abacavir.

The choice of initial ART had little impact on weight gain. INSTIs or TAF were not independently associated with weight change after ART initiation, but EFV and TDF were.