CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

prior antiretroviral (ART) regimen. This exploratory post-hoc analysis examined the impact of pre-existing resistance-associated mutations (RAMs) on the virologic response to DOR/ISL in these trials, focusing on M184V/I and other RAMs in reverse transcriptase. Methods: MK8591A-017 (P017; NCT04223778) was an open-label study in adults receiving any oral 2- or 3-drug ART regimen. MK8591A-018 (P018; NCT04223791) was a double-blind study in adults receiving bictegravir/ emtricitabine/tenofovir alafenamide (B/F/TAF). Participants with HIV-1 RNA <50 copies/mL and no known treatment failure or DOR resistance at baseline were randomized (1:1) to switch to once-daily DOR/ISL (100/0.75mg) or to continue baseline ART (bART) in P017 or B/F/TAF in P018; at week 48, the P017 bART group switched to open-label DOR/ISL. RAMs present at baseline in HIV proviral DNA were identified by Monogram Bioscience (GenoSure Archive assay). Genotypic resistance analyses were based on IAS-USA drug resistance mutation lists for approved ART and other mutations reported in the scientific literature. Results: Baseline resistance data were available for ~90% of study participants. Of the 889 participants who received DOR/ISL in P017 or P018 and had baseline resistance data available, 46 (5.2%) had M184M/I/V at baseline; none of these participants had confirmed viremia (CV; 2 consecutive HIV-1 RNA ≥200 copies/mL 2-4 weeks apart) or low-level viremia (LLV; 2 consecutive HIV-1 RNA ≥50 and <200 copies/mL 2-4 week apart) while receiving DOR/ISL, and 2/46 (4.3%) had ≥1 viral blips (HIV-1 RNA ≥50 copies/mL followed by <50 copies/mL at next measurement). Twenty participants (6.5%) in the bART group had M184M/I/V at baseline: 2/20 (10%) developed CV, and none had LLV or viral blips. Twelve participants (4.3%) in the B/F/TAF group had M184M/I/V at baseline: none developed CV or LLV, and 1/12 (8.3%) had ≥1 viral blips. NNRTI RAMs were present at baseline in 287 (32.3%) of 889 DOR/ISL participants, 100 (32.6%) bART participants, and 85 (30.4%) B/F/TAF participants. Among participants with NNRTI RAMs, virologic outcomes were similar in the DOR/ISL and comparator groups. Conclusion: Switching to DOR/ISL 100/0.75mg maintains viral suppression for up to 96 weeks regardless of archived M184I/V or NNRTI RAMs in proviral DNA. The figure, table, or graphic for this abstract has been removed. Longitudinal Analysis of Preexisting Resistance-Associated Mutations Prior to B/F/TAF Switch Michelle L D'Antoni , Kristen Andreatta, Silvia Chang, Jason Hindman, Laurie Background: Preexisting resistance can affect antiretroviral (ARV) efficacy. Circulating HIV-1 variants with drug resistance-associated mutations (RAMs) can be archived in viral reservoirs, where they can persist and re-emerge. Given the dynamic properties of the latent reservoir, detection of these RAMs over time has not been well defined. Methods: Participants from bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) switch studies (4449, 4030, 4580; virologic suppression [≥3-6 months]; no prior virologic failure) with HIV-1 RNA or proviral HIV-1 DNA genotyping (population reporting) from ≥2 pre-switch timepoints were included. For 2 timepoints only, RAMs in protease, reverse transcriptase and integrase, and other substitutions (accessory, polymorphisms) were categorized as detected 100% (2 out of 2 tests) or 50% (1 out of 2 tests; subcategorized as detection lost or gained) of the time. For >2 timepoints, RAMs were categorized as lost, gained, persistent, or fluctuating. Time between first and last tests was reported in median years (y). Nonparametric statistics were used. Results: In all, 235 participants had evaluable data (longitudinal tracking of ≥1 RAM or other substitution). For 206 participants with 2 timepoints, 103 of 256 RAMs reported (40.2%) had 100% detection, and 153 (59.8%) had 50% detection, with 95 (62.1%) gained and 58 (37.9%) lost (Figure). 100% detection was lower for RAMs versus other substitutions (n=3329/4339 [76.7%]; p<0.0001). Time between tests was not different between RAMs with 100% and 50% detection: 7.7 y (quartile 1-3 [IQR] 3.2-11.1) vs 5.9 y (IQR 3.2-9.7), respectively (p=0.06). For 29 participants with >2 timepoints (median 3 reports, 9.3 y [IQR 5.7-13.9] between first and last tests), 66 RAMs were categorized as fluctuating (48.5%), gained (25.8%), persistent (15.2%), or, least common, lost (10.6%). K103N (n=10) and M184V/I (n=16) were predominantly fluctuating (60.0% and 43.8%, respectively) and only lost in 10.0% and 6.3% of cases, respectively. Conclusion: Some RAMs were consistently reported, but the majority were newly detected or fluctuated and did not disappear significantly over time, VanderVeen, Christian Callebaut Gilead Sciences, Inc, Foster City, CA, USA

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Impact of Archived Minority Populations With M184V/I on DTG/3TC for Maintenance of Viral Suppression Rosa De Miguel Buckley 1 , Mayra Sigcha 2 , Maria de Lagarde 2 , Jose Luis Blanco 3 , Rocio Montejano 1 , Angela Gutiérrez Liarte 4 , Esperanza Cañas-Ruano 5 , Arkaitz Imaz 6 , Cristina Hernández 7 , Antonio Ocampo Hermida 8 , Pedro Gil 9 , Rafael Delgado 2 , Federico Pulido 2 , Jose R. Arribas 1 , for the VOLVER-GESIDA 11820 Study Group 1 La Paz University Hospital, Madrid, Spain, 2 Hospital Universitario 12 de Octubre, Madrid, Spain, 3 Hospital Clinic of Barcelona, Barcelona, Spain, 4 Hospital Universitario de La Princesa, Madrid, Spain, 5 Hospital del Mar, Barcelona, Spain, 6 Bellvitge University Hospital, Barcelona, Spain, 7 Hospital Universitario Príncipe de Asturias, Madrid, Spain, 8 Hospital Universitario Alvaro Cunqueiro, Vigo, Spain, 9 Fundación SEIMC-GeSIDA, Madrid, Spain Background: There is limited evidence on the utility of proviral DNA sequencing to guide treatment changes in virologically suppressed persons with HIV (PWH) and prior virologic failures. VOLVER clinical trial aimed to evaluate if proviral DNA could assist in switching to dolutegravir/lamivudine (DTG/3TC) in PWH with history of 3TC resistance. Methods: Open-label single-arm multicentric clinical trial of virologically suppressed PWH with past 3TC resistance. Participants switched to DTG/3TC if population sequencing of proviral DNA at baseline did not detect the M184V/I mutation. Proviral DNA next-generation sequencing (NGS) was performed from baseline samples. Primary endpoint was proportion of participants with HIV-1 RNA viral load (VL) ≥50 copies/mL at 48 weeks (intention-to-treat-exposed, FDA snapshot). NCT04880785. Results: 121 participants with a mean virological suppression of 9 years switched to DTG/3TC. 109 participants (90.1%, 95%CI: 83%-95%) had a VL <50 copies/mL at week 48, 12 premature discontinuations (4 with VL≥50 copies/mL). Baseline proviral DNA NGS (using a >5% detection threshold) data is available for 106 participants: 21 (19.8%) had M184V/I (184V: 18, 184I: 3; mean frequency 28%, range: 8-51%), 1 had K65R, 4 had thymidine analogue associated mutations (TAMs), and 3 had other nucleoside associated mutations (NAMs) – no participant had both M184V/I and TAMs. Outcomes at 48 weeks of the 21 participants with M184V/I were: all had VL<50 copies/mL, even though 2 (9.5%) withdrew prematurely due to adverse events. Among participants who withdrew the study with VL≥50 copies/mL with baseline NGS data (3/4), none had M184V/I by NGS at baseline, including 2 who discontinued due to protocol virologic withdrawal criteria (one had NAMs 67G and 70E at baseline in NGS). At virologic withdrawal the only amplifiable sample (139 copies/mL) showed no emerging integrase resistance and the M184V with a 17% frequency by NGS in plasma RNA. After baseline, 10/103 participants with NGS data and VL<50 copies/mL at week 48 had a transient viral rebound: 1/21 with 184V/I (4.8%), 0/8 with other mutations and 9/74 without mutations (12.2%). Conclusion: In this clinical trial of DTG/3TC for maintenance of virological suppression detecting M184V/I in proviral DNA with NGS at baseline did not predict virologic outcomes. Our results question the use of proviral DNA NGS to guide switches to DTG/3TC in PWH with a history of lamivudine resistance. Switching to Doravirine/Islatravir Maintains Viral Suppression Regardless of Archived Mutations Ernest Asante-Appiah , Steffy Joseph, Jingwen Chai, Megan Green, Karen Eves, Prachi Nair, Mandy Su, Stephanie Olsen Klopfer, Todd Alan Correll, Jason Yun Kim, Michelle Candice Fox Merck Research Laboratories, Rahway, NJ, USA Background: In 2 phase 3 clinical trials, switching to the 2-drug combination doravirine/islatravir (DOR/ISL) 100/0.75mg was non-inferior to continuing the

Poster Abstracts

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