CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

dolutegravir, CAB may have different effects on weight/weight gain, or the interaction between HIV-infection and INI treatment may be an important contributor to observed weight gain as part of ART.

Oral Abstracts


Raphael J. Landovitz 1 , Sahar Z. Zangeneh 2 , Gordon Chau 2 , Beatriz Grinsztejn 3 , Joseph J. Eron 4 , Halima Dawood 5 , Manya Magnus 6 , Albert Y. Liu 7 , Ravindre Panchia 8 , Mina C. Hosseinipour 9 , David A. Margolis 10 , Adeola Adeyeye 11 , Marybeth McCauley 12 , Myron S. Cohen 4 , Judith S. Currier 1 1 University of California Los Angeles, Los Angeles, CA, USA, 2 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 3 Institute Nacional de Infectologia Evandro Chagas (INI/Fiocruz), Rio de Janeiro, Brazil, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 University of KwaZulu-Natal, Durban, South Africa, 6 George Washington University, Washington, DC, USA, 7 San Francisco Department of Public Health, San Francisco, CA, USA, 8 Chris Hani Baragwanath Hospital, Johannesburg, South Africa, 9 University of North Carolina Project–Malawi, Lilongwe, Malawi, 10 ViiV Healthcare, Research Triangle Park, NC, USA, 11 DAIDS, NIAID, Bethesda, MD, USA, 12 FHI 360, Washington, DC, USA Background: In people living with HIV, ART treatment with regimens containing integrase inhibitors (INIs) has been associated with weight gain and increased waist circumference, raising concerns about possible future risk for metabolic and cardiovascular disease. These changes have been associated with female sex, non-white individuals, and those with higher baseline BMI. HPTN 077, a Phase 2a randomized placebo-controlled study of two dose/dose- interval regimens of cabotegravir, enrolled HIV-uninfected participants from 8 sites in the US (4), Brazil (1), and sub-Saharan Africa (3). 199 participants were enrolled and randomized 3:1 to active CAB or placebo and received oral CAB 30mg or placebo (PBO) QD x 4 weeks, a one-week washout, and then sequential injections of CAB LA or 0.9% saline PBO fromWeek (W) 5 through W41. Methods: We measured weight at study entry (W0), during oral study product administration (W2, W4) and during injectable study product administration (W5, 17, 19, 29/33, and 41). Age, race/ethnicity, sex at birth, injectable dosing cohort, smoking status, and BMI were assessed at baseline. Longitudinal models fitted via generalized estimating equations (GEE) were used to assess marginal effects of study arm on weight over time. Wilcoxon rank sum tests were used to compare medians of numeric variables and chi-square tests were used to compare frequencies of categorical variables. Results: The Table shows median weights at W0 and W41 overall, and changes from baseline (W0-W41) by covariates of interest. Median weight change over 41 weeks was +1.1 kg (IQR -0.9, 3.0) in the CAB arm and +1.0 kg (IQR -1.2, 3.2) in the PBO arm (p=.66). In longitudinal statistical analyses, no statistically significant differences were found in change in weight fromW0 to 41 in CAB vs. PBO treated participants in aggregate, by sex, dosing cohort, age, race/ ethnicity, smoking status, BMI, nor by baseline BMI category. No differences in weight change for CAB vs. PBO were seen for W0-4 and W5-41 separately. Conclusion: In this moderately sized global cohort of 199 HIV-uninfected males and females, there was no difference in weight change for participants receiving CAB compared to PBO-treated participants. Although structurally similar to

35 ASSESSING THE PROBIOTIC EFFECT IN TREATED HIV: RESULTS OF ACTG A5350 Edgar T. Overton 1 , Eunice Yeh 2 , Rachel Presti 3 , Jeffrey Jacobson 4 , Brett Williams 5 , Cara Wilson 6 , Alan Landay 5 , Jason Brenchley 7 , Michael Dube 8 , Carl Fichtenbaum 9 , Netanya S. Utay 10 , Douglas W. Kitch 2 , Adriana Andrade 11 , for the ACTG A5350 Study Team 1 University of Alabama at Birmingham, Birmingham, AL, USA, 2 Harvard University, Boston, MA, USA, 3 Washington University in St Louis, St Louis, MO, USA, 4 Temple University, Philadelphia, PA, USA, 5 Rush University, Chicago, IL, USA, 6 University of Colorado, Aurora, CO, USA, 7 NIH, Bethesda, MD, USA, 8 University of Southern California, Los Angeles, CA, USA, 9 University of Cincinnati, Cincinnati, OH, USA, 10 University of Texas at Houston, Houston, TX, USA, 11 NIH, Rockville, MD, USA Background: HIV alters gastrointestinal (GI) tract permeability, GI lymphoid tissue structure and function, contributing to systemic inflammation. In inflammatory bowel diseases, probiotics can resolve gastrointestinal symptoms and reduce local and systemic inflammation. In this trial, we evaluated whether the probiotic Visbiome Extra Strength (ES) reduced measures of systemic inflammation in persons with HIV (PWH). Methods: A5350, a phase II, randomized, double-blind, two-arm, placebo- controlled study, evaluated changes in soluble inflammatory markers after 24 weeks of probiotic Visbiome ES, and the safety/ tolerability in PWH on antiretroviral therapy (ART). Primary endpoint was change in sCD14 levels; secondary measures included D-dimer, Kynurenine to Tryptophan (KT) ratio, CD4 count, & CD4/CD8 ratio. Mean changes were compared between arms with a 2-sample t-test. Per-protocol analysis included all randomized participants with baseline & week 25/26 sCD14 measurements, remained on study product through week 26 with >50% adherence, no use of prohibited medications, without confirmed virologic failure, and did not experience inflammatory conditions, receive vaccines, or have concurrent illness. Results: Overall, 93 participants (46 placebo, 47 Visbiome ES) enrolled; 86% men, 55%white, 42% black, 20% Hispanic/Latino; median (Q1, Q3) age was 51 (45, 56) years, BMI was 27.1 (24.2, 30.7) kg/m2, CD4 count was 712 (542, 893) cells/mm3 and 99% had HIV-1 RNA <40 copies/mL; one participant had 48 copies/mL. Overall, 25 participants reported adverse events: (8 [19%] placebo; 17 [36%] Visbiome ES) (p=0.098). Excluding 19 participants who did not complete study treatment and one virologic failure, 73 participants (31 placebo; 42 Visbiome ES) remained in the per-protocol population. The mean change (95% CI) in sCD14 from baseline to week 25/26 was 92.3 (-48.5, 233)


CROI 2019

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