CROI 2020 Abstract eBook

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Poster Abstracts

493 VIROLOGIC OUTCOMES BY RESISTANCE CATEGORY AND PRETREATMENT IN THE DUALIS STUDY Eva Wolf 1 , Christoph Boesecke 2 , Annamaria Balogh 1 , Helen Bidner 3 , Christiane Cordes 4 , Hans Heiken 5 , Ivanka Krznaric 6 , Tim Kümmerle 7 , Jochen Schneider 8 , Christoph D. Spinner 8 , for the DUALIS Study Group 1 MUC Research, Munich, Germany, 2 University of Bonn, Bonn, Germany, 3 Muenchner Studienzentrum, Munich, Germany, 4 Praxis Cordes, Berlin, Germany, 5 Medizinische Hochschule Hannover, Hannover, Germany, 6 Center for Infectious Disease Research, Berlin, Germany, 7 Praxis am Ebertplatz, Cologne, Germany, 8 Klinikum rechts der Isar, Munich, Germany Background: Advances in potency and resistance barrier of antiretroviral drugs for HIV infection and evidence from recent randomized clinical trials (RCTs) support the use of dual therapy at least in specific patient populations. Both, Dolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretroviral drugs with a high resistance barrier. DUALIS, a phase IIIb, open-label RCT demonstrated non-inferiority of a switch to DTG+bDRV (2DR) versus continuous 2NRTI+bDRV (3DR) in virologically suppressed people living with HIV (PLWH) with week 48 virologic response rates of 86% (2DR) and 88% (3DR). Methods: Post-hoc analysis of virologic outcomes in DUALIS with respect to treatment history and HIV drug resistance. Among study inclusion criteria was an HIV-RNA level <50 cps/mL for ≥24 weeks (one blip accepted); any history/presence of drug resistance other than INSTI or bDRV was not exclusionary. Documentation of resistance-associated mutations (RAMs) was based on the Stanford HIVdb mutation list involving specific additional RAMs. Virologic outcomes in subgroups include the primary endpoint (PE, i.e. %with HIV-RNA<50cps/mL at week 48) and % of patients with ≥50 cps/mL (i.e. data in window and ≥50 cps/mL or discontinuation for lack of efficacy or discontinuation for other reason and ≥50 cps/mL). Results: The ITTe set included 263 subjects (2DR n=131, 3DR n=132): 90.1% males, median age 48 years, CDC stage C 29.7%, CD4 nadir<200/µl 47.0%; median time on ART 5.3 years, 27.4%with ≥2 ART changes, 8.4%with prior INSTI use; 20.9% and 11.0% had a history of ≥2 NRTI and ≥2 PI changes, respectively. NRTI, NNRTI and (minor or major) PI RAMS were observed in 9.1, 12.9, and 26.6% (major PI RAMS 3.4%), respectively. Resistance categories and PE analyses within subgroups are shown in Table 1 with response rates ≥80% across groups. Response rates with major and/or minor RAMs were 88.9% on 2DR and 95.5% on 3DR versus 84.9% (2DR) and 84.1% (3DR) without documented RAMs. No patient with major/minor RAMs in either group had ≥50 HIV-RNA cps/mL at last follow-up. No emergence of RAMs during follow-up was observed. Conclusion: As shown in the DUALIS study, dual therapy with DTG+bDRV tends to be an effective treatment option with no treatment-emergent resistance for PLWH on suppressive first- or further-line ART with or without evidence of pre-existing NRTI, NNRTI or PI RAMs.

494 ONCE-DAILY ETRAVIRINE/RALTEGRAVIR (400/800 MG) AS MAINTENANCE REGIMEN Romain Palich 1 , Yasmine Dudoit 1 , Gilles Peytavin 2 , Minh Le 2 , Cathia Soulie 3 , Roland Tubiana 1 , Clotilde Allavena 4 , Laurence Weiss 5 , Ana Montoya Ferrer 6 , Claudine Duvivier 7 , Olivier Bouchaud 8 , Julie Bottero 9 , Anne-Geneviève Marcelin 1 , Lambert Assoumou 10 , Christine Katlama 1 1 AP–HP, Hôpitaux Universitaires Pitié Salpêtrière, Paris, France, 2 AP–HP, Hôpital Bichat-Claude Bernard, Paris, France, 3 INSERM, Paris, France, 4 CHU de Nantes, Nantes, France, 5 Georges Pompidou European Hospital, Paris, France, 6 CHU de Montpellier, Montpellier, France, 7 Necker Hospital, Paris, France, 8 Assistance Publique – Hôpitaux de Paris, Paris, France, 9 AP–HP, Paris, France, 10 Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France Background: The ANRS163-ETRAL study showed 99.4% of virological success rate for etravirine/raltegravir (200/400 mg) twice-daily (ETR/RAL BID) dual therapy in suppressed HIV-infected patients older than 45 years [Katlama C, et al., J Antimicrob Chemother , 2019]. To simplify this regimen, we aimed to assess the efficacy of etravirine/raltegravir (400/800mg) given once-daily (ETR/RAL QD). Methods: Patients with plasma viral load (pVL) <50 copies/mL under ETR/ RAL BID for at least 96 weeks were switched to ETR/RAL QD in this prospective, multicenter, open-label, single arm study. Primary outcome consisted in the rate of virological failure (VF, defined as 2 consecutive pVL >50 copies/mL 2-4 weeks apart or a single value >400 copies/mL) at W48, estimated with the Kaplan- Meier method. Secondary outcomes included tolerance, treatment strategy success rate (defined as absence of VF with no treatment discontinuation), plasma drugs concentrations and resistance profile in case of VF. The objective of the study was to show a VF rate <10%. Results: A total of 111 patients were included with a median (IQR) age: 57 years (52-62), CD4: 710 cells/mm 3 (501-919), CD4 nadir: 183 cells/mm 3 (90-269) and HIV suppression duration: 7.9 years (5.9- 10.7). Two VF occurred at W24 and W48 leading to a VF rate of 2.0% (95%CI [0.5-7.8]). One of both reported poor compliance and were virologically suppressed after ART resumption, with no acquired resistance. The second patient had low etravirine and raltegravir plasma concentrations (C 24h : 365 ng/mL and 71 ng/mL, respectively), with selection of INI associated resistance mutations L74I, G140A and Q148H. Overall 7 patients discontinued ETR/RAL QD for non VF reasons: adverse events (n=3, lethal myocardial infarction, nausea and death), investigator decision (n=2), pregnancy (n=1) and patient decision (n=1), leading to a strategy success rate of 91.7% (95%CI [84.6-95.6]) at W48. Median (IQR) C 24h values of etravirine 400 mg and raltegravir 800 mg QD were 401 ng/mL (286-591) and 51 ng/mL (26-93), respectively. Conclusion: Switching from ETR/RAL BID to QD regimen is highly effective in maintaining virological suppression in HIV-infected patients. This once-daily combination is a good option to avoid protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) in aging patients. 495 PATTERNS OF ADHERENCE IN BICTEGRAVIR- AND DOLUTEGRAVIR-BASED REGIMENS Paul E. Sax 1 , Joseph J. Eron 2 , Andrew Frick 3 , Scott Milligan 4 , Moti Ramgopal 5 , Steven Santiago 6 , Richard A. Elion 7 1 Harvard University, Cambridge, MA, USA, 2 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 3 University of California San Diego, San Diego, CA, USA, 4 Trio Health, La Jolla, CA, USA, 5 Midway Immunology and Research Center, Fort

Poster Abstracts

CROI 2020 175