CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

482 LONG-ACTING CABOTEGRAVIR + RILPIVIRINE FOR HIV TREATMENT: FLAIR WEEK 96 RESULTS Chloe Orkin 1 , Shinichi Oka 2 , Patrick Philibert 3 , Cynthia Brinson 4 , Ayesha Bassa 5 , Denis Gusev 6 , Olaf Degen 7 , Juan González-García 8 , Ronald D’Amico 9 , David Dorey 10 , Sandy Griffith 9 , David A. Margolis 9 , Marty St Clair 9 , Peter E. Williams 11 , William Spreen 9 1 Queen Mary University, London, United Kingdom; 2 National Center for Global Health and Medicine, Tokyo, Japan; 3 Hôpital Européen, Marseille, France; 4 Central Texas Clinical Research, Austin, TX, United States; 5 Mzansi Ethical Research Centre, Middelburg, South Africa; 6 State Medical Center for the Prevention and Control of AIDS and Infectious Diseases, St. Petersburg, Russia; 7 University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; 8 Hospital Universitario La Paz, Madrid, Spain; 9 ViiV Healthcare, Research Triangle Park, NC, United States; 10 GlaxoSmithKline, Mississauga, Ontario, Canada; 11 Janssen Research & Development, Beerse, Belgium Background: Chronic daily oral ART can be lifesaving but also inconvenient, increasing the risks of non-adherence and treatment failure. To address these issues, long-acting (LA) injectable regimens of the INSTI cabotegravir (CAB) and the NNRTI rilpivirine (RPV) are under evaluation. FLAIR (NCT02938520) is a randomized, Phase 3, open-label, multicenter study investigating whether switching to monthly CAB+RPV LA is non-inferior to daily dolutegravir/ abacavir/lamivudine (DTG/ABC/3TC [CAR]) in virologically suppressed adults infected with HIV-1. Methods: ART-naive participants received induction therapy with oral CAR for 20 weeks. After 16 weeks, participants with HIV-1 RNA <50c/mL were eligible to enter the maintenance phase (MP) and were randomized (1:1) to either switch to LA or continue CAR. Those randomized to the LA arm received an oral lead-in of CAB 30mg + RPV 25mg once daily for 4 weeks before receiving monthly injectable CAB+RPV LA. The primary endpoint was viral load ≥50c/ mL at MP Week 48 (W48) by FDA snapshot algorithm (NI margin 6%). Endpoints assessed at MP Week 96 (W96) included viral loads ≥50c/mL and <50c/mL, confirmed virologic failure (CVF; two consecutive viral loads ≥200c/mL), safety, tolerability, and patient satisfaction. Results: From 629 participants who initiated induction therapy, 566 were randomized to either the LA or CAR arm (283/arm). Median age was 34y (11% ≥50y); 22%were female and 74%were white. At W96, 9 (3.2%) participants in each arm had HIV-1 RNA ≥50c/mL, underscoring the non-inferiority established at W48 (Table). For the LA arm, the rate of CVF was unchanged fromW48 at W96 (4 participants [1.4%]); 3 had mutations in the NNRTI + INSTI domains and 1 had no mutations). The CAR arm had 4 CVFs through W96 (vs. 3 through W48); none had mutations. Across both treatment arms, AEs leading to withdrawal were infrequent. Injection site reactions (ISRs) were the most common drug-related AE (86% of participants in the LA arm); their frequency decreased over time. Median ISR duration was 3 days and 99%were Grade 1 or 2. At W96, the LA regimen was associated with a greater treatment satisfaction vs. oral CAR as measured by HIVTSQs. Conclusion: CAB+RPV LA maintained viral suppression with no further CVFs between W48 and W96 and was non-inferior to oral standard of care ART. Although ISRs were frequently reported with CAB+RPV LA, they seldom led to withdrawal, and overall treatment satisfaction was higher than with ART. These results attest to the durability of CAB+RPV LA. 483 DTG+3TC VS DTG+TDF/FTC (GEMINI 1&2): CONFIRMED VIROLOGIC WITHDRAWALS THROUGH WEEK 96 Mark Underwood 1 , Ruolan Wang 1 , Paul Benson 2 , Norma Porteiro 3 , Giuliano Rizzardini 4 , José R. Santos 5 , Rickesh Patel 6 , Justin Koteff 1 , Rimgaile Urbaitye 7 , Joe Horton 8 , Jörg Sievers 6 , Choy Man 1 , Allan Raymond Tenorio 1 , Jean van Wyk 6 1 ViiV Healthcare, Research Triangle Park, NC, USA, 2 Be Well Medical Center, Berkley, MI, USA, 3 Fundación Ideaa, Buenos Aires, Argentina, 4 Luigi Sacco Hospital, Milan, Italy, 5 Fundació Lluita contra la Sida, Badalona, Spain, 6 ViiV Healthcare, Brentford, UK, 7 GlaxoSmithKline, Uxbridge, UK, 8 PAREXEL International, Durham, NC, USA Background: In GEMINI-1&2, the dolutegravir (DTG) + lamivudine (3TC) 2-drug regimen (2DR) is non-inferior to the DTG + tenofovir/emtricitabine (TDF/FTC) 3-drug regimen (3DR) in HIV-1 ART-naïve participants at Weeks 48/96. Eleven participants on 2DR and seven on 3DR met protocol-defined Confirmed Virologic Withdrawal (CVW) criteria through Week 96. We present a detailed description of these CVWs. Methods: Patients were stratified by viral load (VL) ≤/>100,000c/mL and CD4+≤/>200cells/mm 3 . Patients were not eligible if screening HIV-1

target population of ART-naïve patients with CD4 count<200 or AIDS is likely to show a notable reduction in risk of treatment failure in people initiated with dolutegravir vs. boosted-darunavir based therapies.

481 FLOW CYTOMETRIC SCREENING OF HLA-B17 IN HIV+ PATIENTS UNDERGOING ABACAVIR THERAPY

Poster Abstracts

Arianna Gatti 1 , Cristina Ceriani 1 , Bruno Brando 1 , Maurizio Mena 1 , Paolo Viganò 1 , Massimo De Paschale 1 , Pierangelo Clerici 1 1 ASST Ovest Milanese, Legnano, Italy Background: The Abacavir Hypersensitivity Syndrome (AHS) is a life- threatening side effect that can occur in HLA-B*5701+ HIV+ patients treated with Abacavir. Every HIV+ patient eligible for Abacavir therapy must be therefore screened for the presence of the HLA-B*5701 allele and treated only if negative. The B*5701 allele is a member of the HLA-B17 family. HLA-B *5701 typing is mostly based on molecular methods, that are expensive and require a median of 21 days for processing. In this study we have developed a rapid dual- color Flow Cytometric (FC) assay, including anti-B17monoclonal antibody that provides a cheap and sensitive screening for putative HLA-B*5701+ patients Methods: 21 HIV+ patients already SSO-typed for HLA-B*5701 served as positive (6) or negative (15) controls, respectively. Other 437 HIV+ patients were prospectively evaluated for HLA-B17 by FC and their outcome during Abacavir treatment was monitored.Briefly, 50 mL of EDTA blood were stained with 10 mL of unconjugated IgMmonoclonal anti-B17 antigen (OneLambda) in a stain-lyse- and-wash procedure. A secondary PE- anti-mouse IgM was used for indirect immunofluorescence, with anti-CD3 FITC counterstaining. Isotype cold IgM and secondary PE conjugate were used as negative controls. The staining intensity of anti-B17 PE expression on T cells was considered to calculate the reaction cutoff, which was used to discriminate positive and negative cases Results: The agreement between SSO typing and FC assay in the controls was 6/6 for double-positives; one false-positive FC case was due to the cross- reacting antigen B*5702; whereas 14/14 cases were double negatives. Of the prospective 437 cases, 43 (10%) resulted positive for anti-B17, as expected. In 28/43 cases a confirmatory molecular test for HLA-B*5701 allele was performed, which disclosed the B*5701 in 11 patients. In the other 17 cases different alleles of the B17 family were detected, that did not prevent Abacavir therapy. None of the 394 FC B17-negative patients developed AHS during Abacavir administration. Conclusion: In conclusion, the rapid FC assay to evaluate the HLA-B17 phenotype in HIV+ subjects eligible to Abacavir therapy proved reliable to safely screen out HLAB*5701-negative subjects, that represent the majority of cases. Its prospective use allows significant saving of time and money, since it can restrict the confirmative molecular HLA B*5701 typing to the small group of FC positive individuals.

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