CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

transcriptase-inhibitor-(NNRTI) first line was without prior HIV-1 viral load (VL) testing. VL monitoring and drug resistance testing (DRT) are still in scale-up in Malawi. In parallel to the national ART policy change, a prospective enhanced monitoring is conducted in three health centres of the decentralized HIV- programme in rural Chiradzulu District. We present month 6 outcomes. Methods: Inclusion criteria were age >20 years (male), ≥45 years (female) and eligible for TLD by Malawian guidelines. Plasma VL is assessed at 3, 6, 12- and 18-months post TLD-start. Baseline VL was assessed retrospectively from blood collected at inclusion. Virological suppression was defined as VL<50 copies/ml. Participants with VL>50 copies/ml during follow-up receive enhanced adherence counselling and a confirmatory VL test three months later. For virological failure (VF), VL>500 copies/ml at confirmatory test, resistance genotyping (dried blood spots) is done and plasma ARV concentration is measured. Serious adverse events, including treatment discontinuation, are reported. Results: From January–May 2019, 1928 participants were included: 49.1% female, 98.2% TLD-transitioners, with a median 98.2 months (IQR: 50.9 - 135.5) on ART, and 35 ART-initiators. Baseline VL-suppression of transitioners was 94.5% (95%CI: 93.3 - 95.4), 3.3% had VL>1000 copies/ml. Among TLD-initiators, 54% had a CD4 count < 200 cells/μL and the median baseline VL was 5 log 10 (IQR: 4.5 – 5.6). Overall VL suppression was 98% (95%CI: 97.3 - 98.6) at M3 and 98.3% (95%CI: 97.5 – 98.9) at M6 (among 1361 currently assessed). Six (0.4% of tested) transitioners had M6 VF. Among three with currently available DRT, two had DTG resistance (mutation R263K or G118R) in combination with resistance to TDF. Two treatment discontinuations occurred before M3, both due to severe neuropsychiatric events reported as related to dolutegravir. Conclusion: In a cohort highly suppressed on NNRTI-first-line ART, VL- suppression was well maintained at 6 months post-transitioning to TLD, and VL-suppression was high among the few ART-initiators. Of concern are 2 cases of DTG resistance detected after 6 months on TLD, emphasizing the importance of further monitoring and resistance surveillance. RANDOMIZED SWITCH TO B/F/TAF IN AFRICAN AMERICAN ADULTS WITH HIV Debbie P. Hagins 1 , Princy N. Kumar 2 , Michael Saag 3 , Anson K.Wurapa 4 , Indira Brar 5 , Daniel S. Berger 6 , Olayemi Osiyemi 7 , Corrilynn O. Hileman 8 , Moti Ramgopal 9 , Cheryl McDonald 10 , Christiana Blair 11 , Kristen Andreatta 11 , Sean E. Collins 11 , Diana Brainard 11 , Hal Martin 11 1 Chatham CARE Center, Savannah, GA, USA, 2 MedStar Health, Washington, DC, USA, 3 University of Alabama at Birmingham, Birmingham, AL, USA, 4 Infectious Disease Specialists of Atlanta, Atlanta, GA, USA, 5 Henry Ford Hospital, Detroit, MI, USA, 6 Northstar Medical Center, Chicago, IL, USA, 7 Triple O Research Institute, West Palm Beach, FL, USA, 8 Case Western Reserve University, Cleveland, OH, USA, 9 Midway Immunology and Research Center, Fort Pierce, FL, USA, 10 Tarrant County Infectious Disease Associates, Fort Worth, TX, USA, 11 Gilead Sciences, Inc, Foster City, CA, USA Background: Black Americans have the highest rates of HIV/AIDS in the US but are under-represented in HIV medical research. The single-tablet regimen bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) is a guidelines- recommended treatment for HIV. We evaluated the safety and efficacy of switching to B/F/TAF among Black adults. Methods: In the Phase 3 BRAAVE 2020 study, adults with HIV who self- identified as Black or African American and were virologically suppressed on 2 NRTIs plus a 3rd agent were randomized (2:1) to switch to open-label B/F/ TAF once daily or stay on their baseline regimen (SBR). Prior virologic failure was permitted with the exception of failure on an INSTI-based regimen. Prior resistance to NNRTIs, PIs and/or NRTIs was permitted except for K65R/E/N, ≥3 thymidine analogue mutations or T69-insertions; primary INSTI-resistance was excluded. Primary efficacy endpoint was the proportion with HIV-1 RNA ≥50 c/mL at Week (W) 24 (FDA snapshot); noninferiority was assessed through 95% confidence intervals (CI). Change from baseline in CD4 was a secondary endpoint. The HIV-Treatment Satisfaction Questionnaire (HIV-TSQ) was assessed at baseline, W4 and W24. Results: 558 were screened, 495 randomized and treated (B/F/TAF n=330, SBR n=165): 32% cis women, 2% trans women, median age 49 yrs (range 18-79), median HIV treatment duration 10 yrs (IQR 6,17), 11% had M184V/I mutation, 62% lived in the US South. Baseline 3rd agents: INSTIs 61%, NNRTIs 31% and PIs 9%. At W24, 0.6% on B/F/TAF and 1.8% on SBR had HIV-1 RNA ≥50 c/mL (difference -1.2%; 95% CI -4.8% to 0.9%) demonstrating noninferiority of B/F/ TAF. The proportion with HIV-1 RNA <50 c/mL was 96% B/F/TAF and 95% SBR. No participant had treatment emergent resistance to study drugs. The mean

(SD) changes in CD4 were +13 (209) and +1 (171) (p=0.56), median changes in weight 0.9 and 0.2 kg for B/F/TAF and SBR respectively. Study drug related AEs occurred in 10% on B/F/TAF, most were grade 1. Drug related AEs led to discontinuation in 5 participants on B/F/TAF vs 0 on SBR. Participants on B/F/TAF had higher HIV-TSQ scores at W4 and W24 compared to SBR (p<0.001). Conclusion: For Black Americans, switching to B/F/TAF was noninferior to continuing their regimen with high efficacy in both arms. The single-tablet regimen B/F/TAF was safe and effective for people switching from a variety of regimens, including those with pre-existing NRTI resistance, and was associated with greater treatment satisfaction.

Oral Abstracts

37 IMPACT OF ANTI-PD-1 AND ANTI-CTLA-4 ON THE HIV RESERVOIR IN VIVO: THE AMC-095 STUDY Thomas A. Rasmussen 1 , Laskhmi Rajdev 2 , Ajantha Solomon 1 , Ashanti Dantanarayana 1 , Surekha Tennakoon 1 , Socheata Chea 1 , Rachel L.Rutishauser 3 , Danielle Rigau 4 , Shelly Lensing 5 , Sonia Bakkour 6 , Michael P. Busch 6 , Dirk Dittmer 7 , Steven G. Deeks 3 , Christine Durand 4 , Sharon R. Lewin 1 1 Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia, 2 Albert Einstein College of Medicine, Bronx, NY, USA, 3 University of California San Francisco, San Francisco, CA, USA, 4 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5 University of Arkansas for Medical Sciences, Little Rock, AR, USA, 6 Vitalant Research Institute, San Francisco, CA, USA, 7 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Antibodies to PD-1 and CTLA-4 may perturb HIV persistence during antiretroviral therapy (ART) by reversing HIV-latency and/or boosting HIV-specific immunity. We tested this hypothesis in a prospective multi-center clinical trial of individuals on ART who had cancer and received single immune checkpoint blockade (ICB) with nivolumab (anti-PD-1) or combination therapy with nivolumab and ipilimumab (anti-CTLA-4). Methods: This is a substudy of the AIDS Malignancy Consortium-095 Study. ART-suppressed HIV-infected participants with advanced malignancies were assigned to nivolumab (anti-PD-1) 240 mg every two weeks or nivolumab 240 mg every two weeks plus ipilimumab 1 mg/kg (anti-CTLA-4) every 6 weeks. In samples obtained at baseline, within 24 hours and 7 days after the first and fourth dose of ICB and at one late time point after multiple cycles, we quantified cell-associated unspliced (CA US) HIV-RNA and CA HIV-DNA. Plasma HIV-RNA was quantified during the first cycle of ICB using replicate testing using the Aptima HIV-1 Quant assay. Quantitative viral outgrowth assay to estimate the frequency of replication competent HIV was done at baseline and during ICB for a subset of participants. Changes from baseline, including the difference between those on single compared to dual ICB, were tested using non- parametric and parametric statistics (as appropriate) and repeated-measures analysis of variance. Results: Forty participants were included, 36 males and 4 females. Of those, 33 received anti-PD-1 alone and 7 received anti-PD-1 plus anti-CTLA-4. At baseline, median age was 53.0 (IQR 47.0-58.5) and CD4 count was 315 (IQR 227-465). Whereas CA US HIV-RNA did not change from baseline in those receiving anti- PD-1 alone, we detected a median 1.44 fold-increase (IQR 1.16–1.89) within 24 hours of the first dose in participants on combination ICB (P=0.031). This increase was also significantly higher compared to the corresponding change from baseline in those on anti-PD-1 alone (P=0.025). There were no significant changes from baseline in plasma HIV RNA. We also detected no changes during ICB in the level of HIV DNA or the frequency of cells containing replication- competent HIV (n=10). Conclusion: Dual ICB with anti-PD-1 and anti-CTLA-4 induced a larger increase in CA-US HIV RNA than anti-PD-1 alone with no effect on plasma HIV RNA or the latent HIV reservoir.

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CROI 2020