CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Results: 2745 specimens from 2268 HIV-positive and 477 HIV-negative individuals were included in this analysis. Within the 1147 cART treated and virologically suppressed HIV-positive individuals (<50 copies/ml), our study revealed significant gender specific immune activation expression patterns not present in HIV-negative individuals. Levels (pg/mL) of IP-10 (Male= 58.19, Female= 70.45, p <0.0001), sCD163 (M= 232233, F= 252025, p= 0.0001), and sCD25 (M= 337.9, F= 383.3, p= 0.0012) were significantly higher in females compared to males. We next applied Bayesian multilevel logistic regression models to find associations between immune parameters and the presence of co-infections. We observed that the parameters IL-6, IP-10, and CXCL9 were significantly upregulated in patients with tuberculosis (Probability of no association p< 0.01). HCV Bayesian logistic regression model analyses revealed that patients with high levels of IFN-alpha are less frequently infected with HCV (P- = 0.008). Conclusion: Taken all together, we demonstrate the contribution of gender to immune activation in virologically suppressed individuals infected with HIV on cART (<50 copies/ml). Furthermore, elevated immune activation markers in co- infected individuals reveal that co-infections contribute to immune activation.

confirmed virologic failure (VF: VL ≥1000 c/mL); clinical outcomes and adverse events (intent-to-treat). Results: Women comprised 258/545 (47%) of the study population. More women than men were assigned to Cohort A. Median follow-up was 72 weeks. Fewer women than men had virologic suppression at week 48 (table). This trend occurred in all cohorts, including in Cohort A whose participants stayed on their 2nd-line regimen (39% vs 49%) and in Cohorts B, C and D who received novel regimens (83% versus 89%). Significantly more women experienced VF, Grade 3 signs and symptoms, serious adverse events and hospitalizations, but not more frequent Grade 3+ diagnoses or laboratory abnormalities. Conclusion: More women than men entered the study in cohort A, with a resistance profile suggesting they could be suppressed on their current regimen and therefore stayed on that regimen in the study. Regimens including LPV/r or ATV/r frequently failed. The more frequent occurrence of Grade 3 signs and symptoms in women suggests that tolerability issues were under recognized in women on 2nd-line therapy with demonstrated clinical consequences. More work is needed to identify determinants of drug exposure and tolerability in women in LMIC.

Poster Abstracts

519 TENOFOVIR ALAFENAMIDE VS TENOFOVIR DF IN WOMEN: POOLED ANALYSIS OF 7 CLINICAL TRIALS Melanie Thompson 1 , Indira Brar 2 , Cynthia Brinson 3 , Catherine Creticos 4 , Debbie Hagins 5 , Ellen Koenig 6 , Claudia Martorell 7 , Cristina Mussini 8 , Laura Waters 9 , Susan Guo 10 , Ya-Pei Liu 10 , Lauren L. Temme 10 , Devi SenGupta 10 , Moupali Das 10 1 AIDS Research Consortium of Atlanta, Atlanta, GA, USA, 2 Henry Ford Hospital, Detroit, MI, USA, 3 Central Texas Clinical Research, Austin, TX, USA, 4 Howard Brown Health Center, Chicago, IL, USA, 5 Chatham CARE Center, Savannah, GA, USA, 6 Instituto Dominicano de Estudios Virológicos, Santo Domingo, Dominican Republic, 7 Infectious Disease and The Research Institute, Springfield, MA, USA, 8 Azienda Ospedaliera Universitaria Policlinico di Modena, Modena, Italy, 9 Mortimer Market Centre, London, UK, 10 Gilead Sciences, Inc, Foster City, CA, USA Background: Globally, the majority of people living with HIV are cis-women, who are underrepresented in clinical trials. Tenofovir alafenamide (TAF) has demonstrated an improved renal and bone safety profile relative to tenofovir disoproxil fumarate (TDF) in multiple randomized trials with similar efficacy. We pooled 7 studies to evaluate the efficacy and safety of TAF vs. TDF for ART initiation or switch in women. Methods: Data from 779 cis-women in 7 randomized, double-blind clinical trials (2 in treatment-naïve adults, 5 in virologically suppressed adults) through W96 were analyzed. All participants who initiated or switched to TAF-based regimens (elvitegravir/cobicistat/emtricitabine [FTC]/TAF, rilpivirine/FTC/TAF, FTC/TAF, or bictegravir/FTC/TAF) were compared with those who initiated or continued TDF-based regimens. Virologic suppression (VS; HIV-1 RNA <50 c/ mL) rates at W96 were determined by FDA snapshot analysis. Bone mineral density (BMD) and the renal tubular biomarkers urine beta-2-microglobulin (B2m):creatinine (Cr) ratio and retinol binding protein (RBP):Cr ratio are reported at W96. Differences were compared using Wilcoxon rank sum test. Results: A total of 779 cis-women were enrolled (n=429 TAF, n=350 TDF). Treatment-naïve women (WTN) had a median age of 37, 35.4%were black, 26%were Hispanic/Latina, with median HIV-RNA 4.47 log10 c/mL and CD4 365 cells/mm3. Women with VS (WVS) had a median age 47 years, 50%were black, 25%were Hispanic/Latina, with median CD4 711 cells/mm3. Of WTN, 86% (TAF) and 85% (TDF) achieved VS (p=0.71) at W96. VS was maintained in

518 IMPORTANT SEX DIFFERENCES IN OUTCOMES FOR INDIVIDUALS PRESENTING FOR THIRD-LINE ART

Catherine Godfrey 1 , Michael D. Hughes 2 , Justin Ritz 2 , Robert Gross 3 , Robert A. Salata 4 , Rosie Mngqibisa 5 , Carole Wallis 6 , Mumbi Makanga 7 , Marije Van Schalkwyk 8 , Mitch Matoga 9 , Courtney V. Fletcher 10 , Beatriz Grinsztejn 11 , Ann Collier 12 , for the ACTG 5288 Team 1 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA, 2 Harvard University, Boston, MA, USA, 3 University of Pennsylvania, Philadelphia, PA, USA, 4 Case Western Reserve University, Cleveland, OH, USA, 5 Enhancing Care Foundation, Durban, South Africa, 6 Lancet Labs and BARC SA, Johannesburg, South Africa, 7 Kenya Medical Research Institute, Kisumu, Kenya, 8 Stellenbosch University, Cape Town, South Africa, 9 KEMRI–Centre for Global Health Research, Kisumu, Kenya, 10 University of Nebraska, Omaha, NE, USA, 11 Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro. Brazil, 12 University of Washington, Seattle, WA, USA Background: Sex differences in antiretroviral therapy (ART) outcomes and in drug exposure have been reported supporting the conclusion that some ART combinations may not be as well tolerated in women compared to men. We evaluated disparities in outcomes between men and women participating in ACTG A5288, an interventional strategy trial for individuals failing 2nd-line ART in low and middle-income countries (LMIC). Methods: Participants were assigned to cohorts based on resistance profiles and ART history: Cohort A had no LPV/r resistance, susceptibility to at least one NRTI, and stayed on their LPV/r- or ATV/r-based 2nd-line regimen; others with increasing resistance were assigned to Cohorts B, C or D and changed to a regimen that generally included DRV/r, RAL with ETR or best available NRTIs (except for those with DRV/r resistance or prior RAL exposure). The primary endpoint was virologic suppression at week 48 (VL ≤200 c/ml). In this secondary analysis, we evaluated sex differences in the primary endpoint; in

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