CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

transmission networks of resistance, allowing the detection of TC harbouring minority-resistant species not detectable with Sanger.

failure (VF; rebound in HIV-1 RNA ≥50 copies (c)/mL after achieving <50 c/mL or >1 log10 increase from nadir, subsequently confirmed and ≥200 c/mL; or HIV-1 RNA ≥200 c/mL at last visit) underwent genotypic/phenotypic resistance analyses for PR/RT/IN. Participants who did not resuppress (<50 c/mL) were included in the final resistance analysis population (RAP). Results: Preexisting primary resistance-associated mutations (RAMs) were detected in PR (1-3%) and RT (2-10%) across treatment groups, including M184I (n=1), M41L (n=2), and K219N (n=1) in RT, and did not affect virologic suppression through EoS. The final RAP consisted of 14 participants: DTG+F/ TDF group, 7/122 (6%); B/F/TAF group, 6/119 (5%); and DTG+F/TDF to B/F/TAF group, 1/89 (1%). No participants developed primary RAMs, including 6 who had multiple (2-4) confirmed VFs. Another 8 participants who did not qualify for the final RAP had resistance testing during the study. Of these, 1 from the DTG+F/TDF group with reported nonadherence developed K70E in RT at W24 (conferring low-level resistance to TDF) and M184V/I in RT at W36 (conferring resistance to emtricitabine); no others developed resistance to study drugs. Conclusions: Treatment outcomes were not affected by the presence of preexisting nucleos(t)ide reverse transcriptase inhibitor (NRTI) RAMs, and no participant in the final RAP developed resistance to study drugs. One participant in the DTG+F/TDF group with reported nonadherence developed primary NRTI RAMs. Through EoS, B/F/TAF or DTG+F/TDF maintained high rates of HIV-1 virologic suppression. Resistance Analysis of Weekly Islatravir Plus Lenacapavir in People With HIV at 48 Weeks Laurie Vanderveen 1 , Silvia Chang 1 , Lisa Selzer 1 , Tracy Diamond 2 , Ernest Asante Background: Islatravir (ISL), a nucleoside reverse transcriptase (RT) translocation inhibitor, and lenacapavir (LEN), a capsid (CA) inhibitor, have pharmacokinetic profiles supportive of once-weekly (QW) oral dosing. GS US-563-6041 (NCT05052996) is a Phase 2, open-label study evaluating QW ISL+LEN in virologically suppressed people with HIV-1. At Week (W) 48, ISL+LEN maintained high rates (94.2%) of viral suppression (VS; HIV-1 RNA <50 copies/ mL [c/mL]). Here, we report W48 interim HIV-1 resistance analyses. Methods: Participants received either ISL (2 mg QW from Day [D] 1) + LEN (600 mg D1 and D2; then 300 mg QW) orally (n=52) or remained on once-daily oral bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; n=52). Proviral DNA sequencing of HIV-1 protease (PR), RT, and integrase (IN) was performed at screening, and historical genotypes were collected if available. Absence of known primary nucleoside RT inhibitor (NRTI) or non-NRTI (NNRTI) resistance (-R) by genotype was required for eligibility. Genotypic (HIV-1 CA, PR, RT, and IN) and phenotypic resistance analyses were performed at virologic failure (VF; HIV-1 RNA ≥50 c/mL, subsequently confirmed and ≥200 c/mL, or HIV-1 RNA ≥200 c/mL at study drug discontinuation or last visit). Results: Pre-existing primary resistance-associated mutations were detected in the study population, including five participants who enrolled based on historical genotype and were found to have pre-existing resistance on screening archive genotype after enrollment: 4 (3.8%) participants with NRTI-R, 2 (1.9%) with NNRTI-R, 6 (5.8%) with PR inhibitor-R, and 2 (2.0%) with IN strand transfer inhibitor-R ( Table ). Of those with VS at W48 (ISL+LEN: 49/52; B/F/TAF: 48/52), two had pre-existing M184V/I in RT (one per arm). Three participants in the ISL+LEN arm had missing data at W48 and did not meet resistance analysis criteria; all three had VS at their last visit. One participant without archived genotypic resistance (including M184I/V) receiving ISL+LEN with HIV-1 RNA ≥50 c/mL at D1 met criteria for resistance analysis, but did not have treatment-emergent drug resistance, and subsequently resuppressed by W30 while maintaining ISL+LEN. No participants in the B/F/TAF arm met criteria for resistance testing. Conclusions: ISL+LEN maintained high rates of VS, including one participant with pre-existing M184V. No participants with VF developed study drug resistance. These findings support the ongoing evaluation of ISL+LEN as an oral, QW treatment for HIV-1 infection. Appiah 2 , Cyril Llamoso 2 , Martin Rhee 1 , Christian Callebaut 1 1 Gilead Sciences, Inc, Foster City, CA, USA, 2 Merck & Co, Inc, Rahway, NJ, USA

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No Virological Failure in Patients Switched to Doravirine Treatment With Past Resistance Mutations Basma Abdi 1 , Sanaa Saliba 2 , Marc Wirden 1 , Antoine Faycal 1 , Theophile Cocherie 2 , Romain Palich 1 , Luminita Schneider 1 , Sophie Seang 2 , Marc-Antoine Valantin 1 , Valerie Pourcher 1 , Vincent Calvez 1 , Anne-Geneviève Marcelin 1 , Christine Katlama 1 1 Assistance Publique – Hôpitaux de Paris, Paris, France, 2 Pitie Salpetriere Hospital, Paris, France Background: Doravirine (DOR) is licensed in patients living with HIV (PWH) harboring no prior resistance to any NNRTIs. We aimed to evaluate in real life the efficacy of DOR-containing regimen in PWH with prior NNRTIs virological failure and selected NNRTI resistance-associated mutations (RAMs). Methods: This observational single center study included all PWH who have switched to a DOR-containing regimen (two-drug [2-DR] or three-drug regimen [3-DR]) between 30-09-2019 and 01-05-2022, with an HIV-1 RNA ≤50 cp/ mL at the time of switch and the presence of past NNRTI-RAMs identified on cumulated RNA and/or DNA genotypes interpreted using the latest ANRS and Stanford algorithms. Main outcome was the proportion of participants with virologic failure at week 48 and week 96. Secondary outcomes evaluated the rate of viral suppression, the rate of transient virologic blip, RAMs in case of virologic failure, the occurrence of side effects and the rate of DOR-containing regimen discontinuation. Results: A total of 102 patients was analyzed, mostly men (63%), with a median age of 59 years (IQR 51-63). The median time since HIV-1 diagnosis was 26 years (IQR 16-31), and they had been on ART for 22 years (IQR 14-26). Median viral suppression duration was 7 years (IQR 1-11), and the median CD4 T cell count/mm3 was 544 (IQR 352-753). Most PWH were infected with non-B subtype virus (51%). Of the patients analyzed, 25 of 102 (25%) had documented historical RAMs to DOR, with 9 of these 25 cases (36%) showing possible resistance and 16 cases (64%) showing major resistance to this molecule (Table 1). This resistance profile consisted mainly (21/23) of the K103N, Y181C and/or G190A/E reverse transcriptase substitutions. Median time since the last detection of NNRTI-RAMs was 12 years (5-17). Over 2 years follow-up, no virologic failure occurred neither at week 48 (0/87, 0%) nor 96 (0/86, 0%). All 86 patients maintained virologic success either in DOR-3-DR or 2-DR. Conclusions: Our study provides the first large real-world data on the use of DOR-containing regimens with up to 96 weeks of follow-up. NNRTIs drugs are often compromised by cross-resistance within the class, but with the introduction of DOR, which offers protection even in the presence of some resistant variants in the past, there is still hope for the use of this molecule as an option in salvage regimens for patients with a history of specific NNRTIs-RAMS, provided they have been virologically suppressed for a long time. HIV-1 Resistance Analysis of Treatment-Naive People With HIV and HBV Receiving B/F/TAF or DTG+F/TDF Michelle D'Antoni 1 , Archana V. Boopathy 1 , Kristen Andreatta 1 , Silvia Chang 1 , Jason T. Hindman 1 , Anchalee Avihingsanon 2 , Laurie Vanderveen 1 , Christian Callebaut 1 1 Gilead Sciences, Inc, Foster City, CA, USA, 2 HIV-NAT, Thai Red Cross AIDS and Infectious Disease Research Centre, Bangkok, Thailand Background: In the ALLIANCE study (GS-US-380-4458; NCT03547908), bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) was noninferior to dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) at achieving HIV-1 RNA suppression at Week (W) 48 in treatment-naïve adults with HIV-1/hepatitis B virus (HBV) coinfection, with high rates of suppression maintained through End of Study (EoS). We present HIV-1 resistance analyses through EoS for the B/F/TAF group (through the ≥96W randomized phase and 48W of open-label extension [OLE]) and the DTG+F/TDF to B/F/TAF group (switched from DTG+F/TDF to B/F/TAF at OLE start); additionally, we report data for the DTG+F/TDF group through the randomized phase. Methods: Population sequencing of HIV-1 protease (PR) and reverse transcriptase (RT) was performed at screening. Historical PR, RT, and integrase (IN) genotypes were also collected, if available. Participants with virologic The figure, table, or graphic for this abstract has been removed.

Poster Abstracts

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