Risk Factors for Weight Gain Following Switch to Integrase Inhibitor–Based Antiretroviral Therapy

Abstract

Background Treatment initiation with integrase strand transfer inhibitors (INSTIs) has been associated with excess weight gain. Whether similar gains are seen after switch to INSTIs among virologically suppressed persons is less clear. We assessed pre/post-INSTI weight changes from AIDS Clinical Trials Group participants (A5001 and A5322). Methods Participants who were in follow-up from 1997–2017 and switched to INSTI-based antiretroviral regimens were included. Piecewise linear mixed-effects models adjusting for age, sex, race/ethnicity, baseline BMI, nadir and current CD4+ T-cell count, smoking, diabetes and follow-up time with suppressed HIV-1 RNA examined weight and waist circumference change before and after first switch to INSTIs. Linear spline models with a single knot at time of switch accounted for nonlinear trends. Results The 972 participants who switched to INSTIs were 81% male and 50% nonwhite with a median age at switch of 50 years, CD4+ T-cell count 512 cells/μL, and BMI 26.4 kg/m2. Restricting to persons with suppressed HIV-1 RNA at switch (n = 691), women, blacks, and persons ≥60 years experienced greater weight gain in the 2 years after versus before switch. In adjusted models, white or black race, age ≥60, and BMI ≥30 kg/m2 at switch were associated with greater weight gain following switch among women; age ≥60 was the greatest risk factor among men. Trends for waist circumference were similar. Conclusions Yearly weight gain increased following switch to INSTIs, particularly for women, blacks, and persons aged ≥60. Concomitant increases in waist circumference suggest that this weight gain is associated with an increase in fat mass.

Weight gain among treatment‐naïve persons with HIV starting integrase inhibitors compared to non‐nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada

“…Women and persons of black race who received RAL‐based ART experienced greater increases in waist circumference compared to the PI‐based ART recipients. In another study evaluating weight gain following switch to INSTI‐based regimens among virally suppressed ACTG participants in protocols A5001 and A5322, female sex, black race and older age were all associated with greater annualized weight gain after switch to INSTI [26]. Similarly, in the current study we found that female sex, lower baseline weight and lower baseline CD4 were factors associated with significantly higher odds of a >10% weight gain at two and five years after ART initiation.…”

HIV and antiretroviral therapy-related fat alterations

“…Differences in gender (mainly men) and ethnicity (mainly white) could partly explain this result. By contrast, an analysis of 691 patients with virologic suppression in the ACTG A5551 or A5332 studies from 2007 to 2017 found that women, black people and persons aged ≥60 years experienced a greater rate of weight gain in the 2 years after a switch to an INSTI-based regimen than before the switch 74 . Additionally, in the ANRS163 ETRAL study, 165 persons with viral suppression who switched from a PI to raltegravir and etravirine had a 12% increase in DXA-assessed total, trunk and limb fat but not in lean mass after 96 weeks 75,76 .…”

HIV antiretroviral drugs, dolutegravir, maraviroc and ritonavir-boosted atazanavir use different pathways to affect inflammation, senescence and insulin sensitivity in human coronary endothelial cells

“…However, recently, several reports revealed treatment with that some INSTIs resulted in weight gain, both in ART-initiated and ART-experienced patients switched off PIs to INSTI [12,13,[17][18][19][20][21][22]. This may represent an undesirable effect placing patients at higher risk for cardiovascular and metabolic complications on the long term.…”