CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

738

Bictegravir + Lenacapavir: Baseline and Week 48 Resistance in ARTISTRY-1 Phase II Nicolas Margot, Nina Pennetzdorfer, Vidula Naik, Mauricio Montezuma, Peter Sklar, Christian Callebaut Gilead Sciences, Inc, Foster City, CA, USA Background: ARTISTRY-1 is a Phase 2/3 study evaluating the safety and efficacy of the complete regimen of the capsid inhibitor lenacapavir (LEN) given with the integrase strand-transfer inhibitor (INSTI) bictegravir (BIC) compared to remaining on a complex multi-tablet regimen. Virologically suppressed participants with no known INSTI resistance mutations were enrolled in the Phase 2 portion. At Week 48, BIC+LEN showed high efficacy in maintaining viral suppression. Here we describe the resistance profile of participants at baseline and Week 48. Methods: The presence of HIV-1 resistance-associated mutations (RAMs) was assessed using historical genotypic reports (HGR) and retrospective proviral DNA analysis of Day 1 samples (GenoSure Archive, Monogram). The impact of baseline RAMs on response at Week 48 was evaluated. Post-baseline resistance was assessed in participants with rebound (confirmed HIV-1 RNA ≥ 50 c/mL or last visit ≥ 50 c/mL; analyzed if ≥ 200 c/mL) using assays from Monogram or Seq-IT. Phenotypic assays were also conducted. Results: Baseline HIV-1 genotypic resistance from HGR and/or proviral DNA analyses were obtained from 98% of participants (125/128). Resistance to NRTI, NNRTI, and PI was present in 81%, 65%, and 46% of participants, respectively; 11% of participants had primary INSTI RAMs (proviral DNA analysis only). The presence of baseline RAMs did not affect efficacy at Week 48. A single participant met the criteria for resistance testing; no INSTI mutation was observed, and sequencing of CA identified a novel substitution at CA N74 (N74T) as treatment-emergent, with 2.1-fold decrease in LEN susceptibility. This participant had known NRTI, NNRTI, and PI resistance. Though he had viral load (VL) <50 c/mL at screening, VL was detectable at baseline. He had been on a complex regimen of DRV/r bid+DTG bid+MVC prior to switching to BIC+LEN. Data on prior INSTI use or VL/genotype while on INSTI were not available. On study, he experienced viral load blips and confirmed virologic rebound (VL 305 c/mL at Week 48). This participant resuppressed on a regimen of LEN SC+DTG bid+MVC. Conclusions: The frequency of baseline drug resistance in ARTISTRY-1 was high, but did not affect the efficacy of BIC+LEN in virologically suppressed participants. On-treatment low-level LEN resistance was observed in 1 participant who resuppressed on a LEN-containing regimen. These data underscore the potential of the use of once-daily BIC and LEN to optimize therapy in people receiving a complex ART regimen. Real-World Robustness of B/F/TAF at Virologic Failure in the ANRS-CO3 AquiVIH-NA Cohort Pantxika Bellecave 1 , Alaric Peyrouny-Mazeau 2 , Olivier Leleux 2 , Mojgan Hessamfar 3 , Gwenael Le Moal 4 , Didier Neau 1 , Laure Alleman 5 , Charles Cazanave 1 , Estibaliz Lazaro 1 , Pierre Duffau 1 , Marie-Anne Vandenhende 1 , Bernard Castan 6 , Fabrice Bonnet 1 , Camille Tumiotto 1 , for the ANRS-CO3-AquiVIH-NA Cohort 1 Bordeaux University Hospital, Bordeaux, France, 2 University of Bordeaux, Bordeaux, France, 3 CHU de Bordeaux, Bordeaux, France, 4 Centre Hospitalier Universitaire de Poitiers, Poitiers, France, 5 Centre Hospitalier de la Côte Basque, Bayonne, France, 6 Centre Hospitalier de Périgueux, Périgueux, France Background: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a high potent and simplified antiretroviral therapy (ART) regimen as shown by clinical trials. However, real-world evidence in individuals experiencing a virologic failure (VF) remains limited. We investigated the virological outcomes in participants who experienced VF after switching to B/F/TAF. Methods: We conducted a retrospective study using data from the French regional prospective cohort ANRS-CO3-AquiVIH-NA. Participants who switched to B/F/TAF between 2018/01/01 and 2021/12/31 with a follow-up (FU) up to 65 months and with a genotypic resistance test (GRT) available before B/F/ TAF initiation were included. VF was defined as either 2 consecutive HIV-1 viral loads (VL)>50 cp/mL or 1 VL>1000 cp/mL. GRTs were performed using Sanger sequencing and interpreted using the v34 ANRS resistance algorithm. We described the virological outcomes at the last FU visit or at treatment discontinuation. Results: Of 636 participants with available GRT at B/F/TAF initiation, 55/636 (8.6%) experienced VF during the study period. Among those, 22/55 were unsuppressed at baseline; with a median [min; max] VL of 140 cp/ml [55; 599,503]. GRTs were performed in 46/55 (83.6%) participants at the time of VF.

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Virological Success on InSTI-Based ART Despite Archived InSTI DRMs Yanis Merad 1 , Alice-Andrée Mariaggi 2 , Marina Karmochkine 2 , Jean-Paul Viard 2 , Caroline Charre 3 1 Hospices Civils de Lyon, Lyon, France, 2 Assistance Publique – Hôpitaux de Paris, Paris, France, 3 Cochin Hospital, Paris, France Background: The relevance of drug resistance mutation (DRM) detection in HIV-1 proviral sequencing for the prediction of virological success on antiretroviral therapy (ART) remains unclear. In this retrospective study, we examined archived INSTI DRMs in people with HIV (PWH) virologically suppressed on INSTI-based regimens. Methods: PWH with at least one HIV-1 integrase proviral sequencing were screened for inclusion. HIV-1 DNA integrase was sequenced using the Sentosa SQ HIV Genotyping Assay. Genotypic resistance was analyzed using the Stanford HIV Drug Resistance algorithm. Inclusion criteria were (i) at least one DRM conferring full-class INSTI resistance (T66K, E92Q, G118R, E138A/K/T, G140A/C/S, Q148H/K/R, N155H or R263K) on proviral sequencing and (ii) virological suppression on an INSTI-based regimen at the time of sequencing. Mutational load was calculated as the product of DRM frequency and the amount of total HIV-1 DNA. Proviral defectiveness was presumed based on the detection of stop codons or APOBEC-induced G-to-A hypermutation (using the Los Alamos HIV Database’s Hypermut 2 algorithm). Results: From 883 screened PWH since March 2022, 26 were included for analysis (sex assigned at birth: 69% male; median age: 53.6 [IQR 40–61.8]; subtype B: 58%). Identified DRMs were G140S (n=8), R263K (n=8), E138K (n=7), N155H (n=4), G118R (n=2) and E138A (n=1). Individuals were successfully treated with ART containing DTG (n=17), BIC (n=10), CAB (n=1), EVG (n=1) or RAL (n=1) as shown in figure 1A. DRMs were found in presumably defective proviruses in 18 individuals (69%). A history of virological failure on an INSTI based regimen was reported for 10 individuals. DRMs previously detected in plasma RNA (n=2) were harbored in presumably intact proviruses. Median total HIV-1 DNA was 2,36 log 10 copies/10 6 leukocytes (IQR 2,24–2,65, n=17). Mutational loads are represented in figure 1B. No virological failure on an INSTI based regimen was reported after proviral DRM detection (median follow-up: 202 days [IQR 105–366]). Conclusions: In virologically suppressed PWH, we found a low frequency of archived INSTI DRMs. They were not accountable for any virological failure on INSTI-based regimens during follow-up, even though some of the mutational loads were notably high. This finding is consistent with the detection of DRMs mostly in presumably defective proviruses. Together, our results suggest that archived INSTI DRMs should be cautiously interpreted and do not preclude virological success on INSTI-based regimens.

Poster Abstracts

739

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CROI 2025 214