Recent reports describe greater weight gain among antiretroviral therapy (ART)-naïve persons with HIV (PWH) starting integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) vs. protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART. Since many PWH have switched from non-INSTI to INSTI-based regimens, we assessed weight over time among PWH switched to an INSTI regimen (before the introduction of tenofovir alafenamide) in the multisite North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).
Adult PWH with >2 years of no HIV-1 RNA measurements >1000 copies/mL prior to and following the switch from an NNRTI- or PI- to INSTI-based ART were included. Piecewise linear mixed models with random intercepts and slopes estimated pre- and post-switch weight over time, adjusting for age, sex, race, cohort site, HIV acquisition mode, calendar year, pre-switch ART class (NNRTI vs. PI), and CD4+ T cell count and BMI at the time of switch. We included interaction terms for sex, race, and age (<50 vs. >=50) with regimen and time.
A total of 2255 participants switched to an INSTI and had the required follow-up time; of these, 877 met viral suppression criteria and were included. At switch, median age was 50 years, BMI 26 kg/m2, and CD4+ count 619 cells/mm3; 83% were men, and 59% were white. Overall, the annualized weight slope among PI users was +0.80 (95% CI: 0.57 to 1.04) kg/year before switch, which decreased by -0.46 (-0.67 to -0.26) after switch to an INSTI (absolute slope +0.34 kg/year after switch). For NNRTI users, the slope before switch was +0.63 (0.34 to 0.91) kg/year, increasing by +0.50 (0.23 to 0.77) after switch to an INSTI (absolute slope +1.13 kg/year after switch). This difference was primarily driven by an increase in the weight slope among women, non-whites, and older PWH in the NNRTI group (table). Among individual INSTI drugs, the slope change after switch from NNRTI was highest for dolutegravir (DTG) at +0.93 (0.39 to 1.46) kg/year vs +0.44 (-0.04 to 0.92) kg/year for elvitegravir and +0.23 (-0.13 to 0.58) kg/year for raltegravir.
Women, non-whites and older PWH with viral suppression had greater annualized weight gain after switch from NNRTI- to INSTI-based ART, which was greatest for dolutegravir, whereas those switched from a PI had slowing of weight gain. These findings may reflect a heterogenous effect of ART class and agent on body weight regulation.