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RISK FACTORS FOR EXCESS WEIGHT GAIN FOLLOWING SWITCH TO INTEGRASE INHIBITOR–BASED ART
Jordan E. Lake1, Kunling Wu2, Kristine M. Erlandson3, Sara H. Bares4, Paula Debroy1, Catherine Godfrey5, John R. Koethe6, Grace A. McComsey7, Frank J. Palella8, Katherine Tassiopoulos2
1University of Texas at Houston, Houston, TX, USA,2Harvard University, Cambridge, MA, USA,3University of Colorado Anschutz Medical Campus, Aurora, CO, USA,4University of Nebraska Medical Center, Omaha, NE, USA,5NIH, Bethesda, MD, USA,6Vanderbilt University, Nashville, TN, USA,7Case Western Reserve University, Cleveland, OH, USA,8Northwestern University, Chicago, IL, USA
Weight gain following antiretroviral therapy (ART) initiation occurs with all modern regimens. Recent real-world reports from small studies suggest that integrase strand transfer inhibitor (INSTI)-based ART may be associated with excess weight gain. We assessed weight gain following switch to INSTI-based ART among AIDS Clinical Trials Group (ACTG) participants in ACTG protocols A5001 and A5322, which provided long-term observational follow-up of individuals enrolled in randomized interventional trials.
A5001 and A5322 participants in follow-up from 1997-2017 who switched to INSTI were included. Within-person weight and waist circumference trajectories were generated, allowing participants to serve as their own controls for estimation of background/age-related weight gain. Piecewise linear mixed effects models adjusting for age, sex, race/ethnicity, parent study baseline BMI and their interactions, nadir CD4+ T cell count, smoking, diabetes and percent follow-up time with suppressed (<200 copies/mL) HIV-1 RNA examined weight and waist circumference change before and after first switch to INSTI. Linear spline models with a single knot accounted for non-linear trends.
Adults (n=972) who switched to INSTI (68% from PI, 31% NNRTI, 2% other non-INSTI at median 7.8 years after parent trial entry) were 81% male and 50% non-white. Median age at switch was 50 years, CD4+ T cell count 511 cells/μL and BMI 26.4 kg/m2; 539 switched to RAL, 222 to EVG and 211 to DTG. When restricted to persons with suppressed HIV-1 RNA at switch (n=691), women, blacks and persons age ≥60 experienced significantly greater weight gain in the 2 years following switch to INSTI vs 2 years prior to switch; men and persons age <40 experienced less weight gain. In adjusted models, white or black race, age ≥60 and BMI ≥30 kg/m2 were associated with greater weight gain following switch among women, whereas age ≥60 was the greatest risk factor among men. Trends for waist circumference were similar (data not shown).
Yearly weight gain increased following switch to INSTI. These increases were particularly significant for women, blacks and persons age ≥60. When compared to pre-switch weight changes on stable suppressive ART and given concomitant increases in waist circumference, these data suggest increases in weight/fat mass greater than expected for age. The cardiometabolic implications of increased weight gain following switch to INSTI need to be established.