CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

673 THE IMPACT OF WEIGHT GAIN AND SEX ON IMMUNE ACTIVATION FOLLOWING INITIATION OF ART

Sara H. Bares 1 , Laura M. Smeaton 2 , Vincent Vu 2 , Beth A. Zavoda-Smith 3 , Sarah E. Scott 3 , Catherine Godfrey 4 , Grace A. McComsey 3 1 University of Nebraska Medical Center, Omaha, NE, USA, 2 Harvard T.H. Chan School of Public Health, Boston, MA, USA, 3 Case Western Reserve University, Cleveland, OH, USA, 4 DAIDS, NIAID, Bethesda, MD, USA Background: Immune activation persists despite suppressive antiretroviral therapy (ART) and may be affected by sex or body composition. We hypothesized that weight gain, sex and BMI would be associated with changes in immune activation following ART initiation and explored these relationships in a selected subset of women and men initiating ART in two large randomized ACTG trials (A5202 and A5257). Methods: A purposeful sampling design selected participants who achieved virologic suppression on ART and either maintained weight within +/- 0.5 kg/ m2 (“maintainers”) or gained 2.6-6.4 kg/m2 (“gainers”) from baseline to 96 weeks. We measured IL-6, sTNF-RI and II, IP-10, hsCRP, sCD14 and sCD163 at weeks 0 and 96. Multivariable linear regression explored associations of weight gain (gainers vs maintainers), sex, and pre-ART BMI with outcomes of pre-ART biomarker concentrations and changes from baseline to week 96, adjusting for baseline age, race/ethnicity, ART regimen, CD4 count and HIV-1 RNA. Results: 340 participants were selected; median pre-ART age 42 years, CD4+ cell count 273 cells/mm3, HIV-1 RNA 4.7 log10 copies/mL; 49%were women, 33%white, 42% black, and 24% Hispanic. Pre-ART biomarker concentrations were similar in women and men (data not shown). While pre-ART BMI was similar between gainers and maintainers (overall and within sex), gainers had significantly lower pre-ART CD4 vs maintainers. In adjusted models among those with normal pre-ART BMI, pre-ART IL-6, sTNF-RII, IP-10, and sCD163 were higher for gainers versus maintainers. Association of weight gain on week 96 changes of these 4 biomarkers differed by sex; women who gained weight had smaller declines in biomarkers compared to men who gained (see Table). For IL-6, for women, gaining weight was associated with attenuating changes by 0.05 (difference between model-based means), whereas for men, gaining weight was associated with increasing changes by 0.13. For sTNF-RII, the association between weight gain and changes in sTNF-RII also varied by pre-ART BMI. Conclusion: Higher pre-treatment immune activation markers are significantly associated with weight gain following ART initiation even after controlling for pre-ART CD4 counts. Weight gain attenuates the decline in several immune activation markers following ART initiation among women; thus, women may be at increased risk for complications of weight gain. Identifying individuals at risk of weight gain may allow for targeted investigation of preventive interventions.

672 INTEGRASE STRAND TRANSFER INHIBITORS ARE ASSOCIATED WITH WEIGHT GAIN IN WOMEN Anne Marie Kerchberger 1 , Anandi N. Sheth 1 , Christine D. Angert 1 , Cyra Christina Mehta 1 , Nathan A. Summers 1 , Igho Ofotokun 1 , Deborah Gustafson 2 , Sheri Weiser 3 , Seble Kassaye 4 , Deborah Konkle-Parker 5 , Anjali Sharma 6 , Adaora Adimora 7 , Hector Bolivar 8 , Cecile D. Lahiri 1 1 Emory University, Atlanta, GA, USA, 2 SUNY Downstate Medical Center, Brooklyn, NY, USA, 3 University of California San Francisco, San Francisco, CA, USA, 4 Georgetown University, Washington, DC, USA, 5 University of Mississippi, Jackson, MS, USA, 6 Albert Einstein College of Medicine, Bronx, NY, USA, 7 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 8 University of Miami, Miami, FL, USA Background: Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is recommended first line for HIV treatment. Studies have suggested individuals who switch to INSTI-ART experience increase in body weight. These changes may be more prominent in women. We evaluated the effect of INSTI use on body weight and measurements in HIV+ women. Methods: Data were collected from 2008-2017 from HIV+ women enrolled in the Women’s Interagency HIV Study (WIHS) with viral load <1000 copies/mL on ART. Women who switched to or added an INSTI to ART (SWAD group) were compared to women who remained on non-INSTI ART (STAY group). Outcomes included changes in body weight; body mass index (BMI); percentage body fat (PBF); circumference of waist, hip, arm, and thigh; blood pressure (BP); and incident diabetes mellitus (DM). Outcomes were measured 6-12 months before and 6-18 months after INSTI switch/add in the SWAD group with comparable time points in the STAY group. Baseline demographic and clinical characteristics for STAY and SWAD groups were compared. Linear regression models compared change over time in each outcome by STAY/SWAD group, adjusted for age, race, WIHS site, education, income, smoking status, and baseline ART regimen. Changes in outcomes were also stratified by INSTI type (dolutegravir or raltegravir/elvitegravir). Results: 1118 WIHS participants (884 STAY and 234 SWAD) were followed for average 2.0 (+/- 0.1) years; mean baseline age was 48.8 (+/- 8.8) years, 61% were Black, and mean CD4 669 (+/- 294) cells/mm3. At baseline, women in SWAD group were more likely to be on protease inhibitor-ART but did not differ from STAY by demographics or body measurements. Compared to the STAY group, the SWAD group experienced 2.14 kg greater increase in weight, 0.78 kg/m² greater increase in BMI, 1.35% greater increase in PBF, and 2.05, 1.87, 0.58, and 0.98 cm greater increases in waist, hip, arm, and thigh circumference, respectively (Table 1). Women in SWAD also had 2.24 and 1.17 mmHg greater change in systolic and diastolic BP. New-onset DM occurred in 4.5% (n=8) in SWAD and 2.2% (n=15) in STAY, p=0.11. No significant differences in outcomes were observed by INSTI type. Conclusion: In a longitudinal study of HIV+ women on ART, a switch to INSTI was associated with significant increases in body weight and measurements, body fat, and blood pressure compared to those remaining on non-INSTI ART. Further research is urgently needed for prevention and management of metabolic effects with INSTI use.

Poster Abstracts

CROI 2019 257