CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

attributable fractions (PAFs) of lifestyles and INSTI regimens in PWH who experienced a 5%weight gain over 4 years. Methods: In an observational cohort study from 2007 to 2019 at Modena HIV Metabolic Clinic, virally suppressed ART-experienced but INSTI-naive PWH were grouped in INSTI-switchers vs non-INSTI on stable ART. Groups were matched for sex, age, 1st visit BMI and follow-up duration. Significant weight gain was defined as an increase of ≥5% from 1st visit weight over follow-up. Physical activity was assessed with International Physical Activity Questionnaire (IPAQ) as metabolic equivalent of task (MET). Daily caloric intake (DCI) was evaluated with a 3 day food diary. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented, using the following dichotomic variables: BMI >25 kg/m 2 vs <25 kg/m 2 , DCI >2500 kcal vs <2500 kcal, IPAQ MET <600 vs MET>600, quitting vs continuing smoking, INSTI vs no-INSTI regimens, and CD4/CD8 ratio <1 vs >1. Results: Of 304 PWH (74%males), mean follow-up was 4.2 years (±1.8 SD), age 54.3 (±7.8 SD) years, median duration since HIV diagnosis 22.3 years (IQR 15.5-27.5), CD4 cell count 716 cells/mL (IQR 564-893);98.7% had undetectable HIV-1 RNA (Table). PAF for weight gain was the greatest for BMI (41%, 24-56, p<0.001), followed by CD4/CD8 ratio (38%, 19-55, p<0.001) and physical activity (33%, 95% CI 8-53, p<0.02). PAF was not significant for DCI (-1%, 9-13, p=0.99), smoking cessation (5%, 0-13, p=0.1) and INSTI switch (9%, -20-33; p<0.51). Conclusion: Our findings suggest that weight gain is mostly influenced by pre- existing weight and low physical activity. High CD4/CD8 ratio suggest additional immunologic mechanisms linked to weight gain.

BMI, AST (but not ALT; alcohol abuse by ICD-10 observed in <4%), lower use of prior PI, and higher use of prior NNRTI. There were no statistically significant differences by NRTI backbone and specific INSTIs between those who gained ≥5% vs those who did not. In MV, pts were less likely to gain ≥5% if they had BSL AST≥30 (relative risk [RR]=0.51 [CI 0.31-0.84], p=0.009) or higher BSL weight (RR=0.99 [CI 0.98-1.00], p=0.034). Conclusion: Of 387 pts switching to INSTIs, over 1/3 lost or maintained weight, over 1/3 experienced weight gain <5%, while remaining 27% experienced gain ≥5% after 12 mo on therapy. UV indicated ≥5% gain was associated with prior regimen components and BSL factors of which only BSL weight and AST remained significant in MV. Future research questions include clinical significance of weight gain thresholds that have implications for morbidity, as well as heterogeneity of responses to ARV agents.

Poster Abstracts

677 DRUG CONCENTRATIONS AND BODY WEIGHT GAIN IN PLWH SWITCHED TO 3TC & DOLUTEGRAVIR (DTG) Charles Burdet 1 , Gilles Peytavin 1 , Minh Le 1 , Roland Landman 1 , Delphine Bachelet 2 , Christine Katlama 3 , François Raffi 4 , André Cabié 5 , Charlotte Charpentier 1 , Aida Benalycherif 6 , Diane Descamps 1 , Yazdan Yazdanpanah 1 , Véronique Joly 1 , for the Lamidol Study Group 1 AP–HP, Hôpital Bichat-Claude Bernard, Paris, France, 2 AP–HP, Paris, France, 3 AP– HP, Hôpitaux Universitaires Pitié Salpêtrière, Paris, France, 4 CHU de Nantes, Nantes, France, 5 CHU Fort de France, Fort de France, Martinique, 6 IMEA, Paris, France Background: Weight gain after initiation of DTG-containing ART has recently been reported in clinical trials and cohorts, but pathophysiology remains unclear. In most switch studies, DTG was associated with a 2-NRTIs backbone. We evaluated changes in body weight in virologically suppressed PLWH switched to 3TC plus DTG dual therapy (ANRS 167 Lamidol trial). Methods: Virologically suppressed patients included in the ANRS 167 Lamidol [Joly et al. Antimicrob. Agents Chemother. , 2019], a single arm study, received 8 weeks DTG (50 mg qd) combined with 2 NRTIs backbone (phase 1, fromW-8 to D0) before switching to DTG/3TC for 48 weeks (phase 2, from D0 to W48, 104 patients). All patients entering phase 2 were evaluated, except for 8 subjects exposed to DTG prior to study entry. Body weight was recorded at each visit i.e. W-8, W-4, D0, W8, W16, W24, W36 and W48. The evolution of weight over time was analyzed using a linear mixed effects model. Total DTG and 3TC plasma concentrations (C min ) were measured at D0, W24 and W48 using UPLC-MS/ MS. The relationships between weight variation between W-8 and W48 and the geometric means of DTG and 3TC concentrations were studied using the Spearman correlation coefficient. Results: 96 patients were evaluated (median age 45.2 years, range 23.9-70.6). 82 (85.4%) were male. Before inclusion in the trial, ART regimen included a PI in 24 patients, a NNRTI in 58 patients and an INSTI other than DTG in 14 patients. Median baseline weight was 73.5 kg (IQR 65-80). Weight gain was 1.15 kg (IC 95% 0.45-1.85, p=0.002) during phase 1 and 1.22 kg (IC 95 1.04-1.40, p<0.0001) during phase 2. Weight gain was significantly more rapid during phase 1 (p<0.0001). There was no relationship between weight variation and geometric means of DTG and 3TC C min . Conclusion: In this population of virologically controlled patients, administration of DTG was associated with significant weight increase. This effect was more important at initial phase of DTG administration when DTG was associated to a 2 NRTIs backbone, but persisted when DTG was combined with 3TC only, and was not related to trough plasma DTG concentrations. These

676 UNDERSTANDING WHO DOES AND DOES NOT GAIN WEIGHT WITH INTEGRASE INHIBITORS (InSTI) Grace A. McComsey 1 , Keri N. Althoff 2 , Todd T. Brown 3 , Joseph J. Eron 4 , Gregory D. Huhn 5 , Anthony Mills 6 , Graeme Moyle 7 , Soodi Navadeh 8 , Janna Radtchenko 9 , Paul E. Sax 10 , Richard A. Elion 11 1 Case Western Reserve University, Cleveland, OH, USA, 2 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 Ruth M. Rothstein CORE Center, Chicago, IL, USA, 6 Men's Health Foundation, Los Angeles, CA, USA, 7 Chelsea and Westminster Hospital, London, UK, 8 Gilead Sciences, Inc, Foster City, CA, USA, 9 Trio Health Analytics, 10 Brigham and Women's Hospital, Boston, MA, USA, 11 George Washington University, Washington, DC, USA Background: Randomized clinical trials have shown greater weight gain with INSTI regimens vs other classes of antiretrovirals. Why do some patients gain weight on INSTI and others do not? Are there synergies with other ARV agents and INSTI? We examine HIV patients (pts) in US clinical care switching to INSTIs and compare those with gain ≥5% body weight vs loss or gain <5% after 12 months (mo) on INSTIs. Methods: A retrospective evaluation of 38000 HIV pts with EMR records selected 2384 virally suppressed pts per protocol. Subgroup analysis was conducted in 387 subjects: pts ≥18 years, switched to INSTI regimens in Jan 2015-Jun 2018 for ≥12 mo, with ≥6 mo history, viral suppression and weights at baseline [BSL] and 12 mo (±2 mo). Univariate analyses [UV] were conducted via chi-square and t-test. Multivariate analysis [MV] with a binary outcome of gain ≥5% at 12 mo was conducted using log binomial model; variables significant in UV and demographics were considered; final model included continuous variables age, BSL weight and categorical BSL AST <30 vs ≥30, use of prior protease inhibitors [PI] and prior non-nucleoside reverse transcriptase Inhibitors [NNRTI]. Results: Of 387 pts switched to INSTIs, 103 (27%) gained ≥5%weight, 140 (36%) lost weight or had 0% change, 144 (37%) gained <5%. In comparison to other study pts, those who gained ≥5% had significantly lower BSL weight,

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