CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

treatment initiated in Fiebig I-III vs. IV-VI using repeated measures analysis adjusting for baseline RNA or DNA. Results: From 2015 to 2017 we enrolled 49 donors with Acute and 34 with Recent HIV. Cohort enrolment/ART initiation occurred at medians of 13/15 days after index donations. Longitudinal HIV reservoir data were available for 18 Fiebig I-III and 42 Fiebig IV-VI subjects. Median plasma RNA was 5.4 log 10 copies/ mL at enrolment, declined to 0.23 log 10 copies/mL, did not differ by Fiebig stage (p=0.56) but was 0.31 log 10 lower in females (p=0.02). Median CA RNA was 3.7 log 10 copies/10 6 PBMC at enrolment, falling to 2.2 log 10 copies/10 6 PBMC, and was 0.64 log 10 higher in Fiebig IV-VI than Fiebig I-III treated-subjects (p=0.002). Median CA total DNA was 1.8 log 10 copies/10 6 PBMC at enrolment, falling to 0.85 log 10 copies/10 6 PBMC with no difference by Fiebig stage (p=0.95). Conclusion: Among clade C HIV-infected donors initiated on ART within 195 days of infection, we observed lower CA HIV RNA in Fiebig I-III vs. Fiebig IV-VI groups, demonstrating a small impact of earlier treatment on long-term reservoir expression, and lower post-ART plasma HIV-1 (single copy assay) in women vs. men. This study demonstrated that a partnership between a national blood service and a treatment NGO can establish early treatment cohorts for subsequent entry into HIV Cure research initiatives. 477 144-WEEK EFFICACY AND SAFETY OF B/F/TAF IN TREATMENT-NAIVE ADULTS ≥50 YRS Anthony Mills 1 , Samir K. Gupta 2 , Cynthia Brinson 3 , Kimberly Workowski 4 , Amanda Clarke 5 , Andrea Antinori 6 , Jeffrey L. Stephens 7 , Ellen Koenig 8 , Jose R. Arribas 9 , David M. Asmuth 10 , Douglas Ward 11 , Jürgen K. Rockstroh 12 , Hailin Huang 13 , Hal Martin 13 , Diana Brainard 13 1 Southern California Men’s Medical Group, Los Angeles, CA, USA, 2 Indiana University, Indianapolis, IN, USA, 3 Central Texas Clinical Research, Austin, TX, USA, 4 Emory University, Atlanta, GA, USA, 5 Brighton & Sussex University Hospitals NHS Trust, Brighton, UK, 6 Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, 7 Mercer University, Macon, GA, USA, 8 Instituto Dominicano de Estudios Virológicos, Santo Domingo, Dominican Republic, 9 Hospital Universitario La Paz, Madrid, Spain, 10 University of California Davis, Davis, CA, USA, 11 Dupont Circle Physicians Group, Washington, DC, USA, 12 Bonn University Hospital, Bonn, Germany, 13 Gilead Sciences, Inc, Foster City, CA, USA Background: As people living with HIV age, identifying effective and safe regimens for older individuals is of heightened importance. The single-tablet regimen bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) may benefit older adults due to its favorable adverse event (AE) profile and few drug interactions. Methods: We conducted two randomized, double blind, phase 3 studies of B/F/ TAF in treatment-naïve adults, Study 1489: B/F/TAF vs dolutegravir, abacavir, and lamivudine (DTG/ABC/3TC) and Study 1490: B/F/TAF vs DTG + F/TAF. A pooled analysis assessed efficacy as the proportion with HIV-1 RNA <50 c/ mL (FDA Snapshot) and safety at Week (W) 144 in adults ≥50 and <50 yrs at baseline. Proteinuria and bone mineral density (BMD) were measured in Study 1489 only. Results: 1274 were randomized and treated (634 B/F/TAF, 315 DTG/ABC/3TC, 325 DTG + F/TAF); 196 were age ≥50 yrs (96 B/F/TAF, 41 DTG/ABC/3TC, 59 DTG + F/TAF) of whom 17%were women, 27% Black, and 15% Latino/Hispanic. Efficacy was high for all treatments (Table). The most common AEs in adults ≥50 were nasopharyngitis (20%, 22%, 25%), diarrhea (19%, 22%, 8%), and upper respiratory tract infection (16%, 17%, 12%). The most common AEs in adults <50 were diarrhea (19%, 18%, 18%), headache (17%, 18%, 19%), and nausea (11%, 26%, 15%). Treatment-related AEs occurred in 24%, 37%, and 29% of participants ≥50; the frequency was 26%, 43% and 29% in participants <50 yrs (p<0.001 for B/F/TAF vs DTG/ABC/3TC). Most treatment related AEs were grade 1. AEs leading to study drug discontinuation for participants ≥50 occurred in 2% on B/F/TAF, 5% on DTG/ABC/3TC and 7% on DTG + F/TAF compared to 1% in each treatment group for participants <50 yrs. For those ≥50 with AEs leading to discontinuation, 1 on B/F/TAF, 1 on DTG/ABC/3TC and 3 on DTG+F/ TAF were treatment-related. In Study 1489, mean % changes in hip and spine BMD, proteinuria, and renal biomarkers were similar between B/F/TAF to DTG/ ABC/3TC. There were small changes from baseline in all treatment groups in fasting lipids. Median weight increased from baseline at W144 with no significant difference between treatment groups (Table). Conclusion: Through three years of treatment, B/F/TAF was highly effective, safe and well tolerated in adults ≥50 yrs with no clinically significant impact on bone or renal safety, fasting lipids or weight. B/F/TAF provides a safe and

effective treatment option for older adults with a low potential for drug-drug interactions.

478 CD4:CD8 NORMALIZATION BY INTEGRASE INHIBITORS AMONG TREATMENT-NAIVE PATIENTS Alice Zhabokritsky 1 , Leah Szadkowski 1 , Alison McClean 2 , Robert S. Hogg 2 , Curtis Cooper 3 , Marina Klein 4 , Zabrina Brumme 2 , Sharon Walmsley 1 , for the CANOC Collaboration 1 University of Toronto, Toronto, ON, Canada, 2 British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada, 3 Ottawa Hospital Research Institute, Ottawa, OT, Canada, 4 McGill University, Montreal, QC, Canada Background: HIV infection leads to selective depletion of CD4+ T cells and an increase in CD8+ T cells resulting in an inverted CD4:CD8 ratio which often persists despite antiretroviral therapy (ART). A low CD4:CD8 ratio is associated with AIDS and non-AIDS related morbidities. A positive association between CD4:CD8 ratio normalization and initiation of raltegravir containing regimens has been observed. We hypothesize that Integrase Strand Transfer Inhibitor (INSTI)-containing regimens are associated with shorter time to CD4:CD8 normalization relative to other ART regimens among treatment naïve patients. Methods: Retrospective analysis of the Canadian Observational Cohort (CANOC), a collaboration of HIV-infected individuals initiating combination ART between 2000 and 2014. Participants starting on 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs)/1 INSTI or a non-INSTI regimen on or after January 1, 2011 with a pre-treatment CD4:CD8 ratio <1.2 and ≥2 follow- up ratios within 6 months of treatment initiation were included. Kaplan Meier estimates were used to describe time to CD4:CD8 ratio normalization (CD4:CD8 ratio ≥1.2 on 2 consecutive measures ≥ 30 days apart). Multivariable proportional hazards models were used to estimate the association between ART class and time to CD4:CD8 normalization. Results: 781 participants were included and followed for a median [IQR] 1.9 [1.0, 2.7] years. Median [IQR] age was 38 [31, 47] and 699 (90%) were men. 235 participants starting on INSTI-containing regimens were more likely to have a higher median [IQR] pre-treatment CD4 count (370 [225, 480] vs. 330 [210, 440], p=0.04) compared to those starting non-INSTI regimens. 35 (15%) participants on INSTI-containing regimens normalized their CD4:CD8 ratio with a 0.21 (95%CI 0.13, 0.28) probability of achieving normalization within 2 years. 63 (12%) of those on non-INSTI regimens normalized with a 0.11 (95%CI 0.08, 0.14) probability of achieving so within 2 years (p<0.01). After adjusting for pre-treatment CD4, viral load, risk factor, hepatitis B and C, those starting INSTI-containing regimens compared to other ART were more likely to achieve normalization (HR=1.75, 95%CI 1.10, 2.77). Conclusion: Our results provide further evidence that initiation of INSTI- containing regimens results in a higher rate of normalization of the CD4:CD8 ratio in ART naïve subjects. Whether this is associated with lower rates of comorbidity or improved survival requires further study.

Poster Abstracts

CROI 2020 168