CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

696

Predictive Factors of Virological Failure After Switching to B/F/TAF (ANRS-CO3-AquiVIH-NA) Alaric Peyrouny-Mazeau 1 , Olivier Leleux 1 , Pantxika Bellecave 2 , Mojgan Hessamfar 2 , Gwenael Le Moal 3 , Didier Neau 2 , Laure Alleman 4 , Charles Cazanave 2 , Estibaliz Lazaro 2 , Pierre Duffau 2 , Marie-Anne Vandenhende 2 , Bernard Castan 5 , Camille Tumiotto 2 , Fabrice Bonnet 2 , for the ANRS-CO3-AquiVIH-NA Cohort 1 University of Bordeaux, Bordeaux, France, 2 Bordeaux University Hospital, Bordeaux, France, 3 Centre Hospitalier Universitaire de Poitiers, Poitiers, France, 4 Centre Hospitalier de la Côte Basque, Bayonne, France, 5 Centre Hospitalier de Périgueux, Périgueux, France Background: Bictegravir/Emtricitabine/Tenofovir alafenamide (B/F/TAF) is a simple highly potent antiretroviral (ART) regimen with a high genetic barrier to resistance. However, real-world evidence in the presence of drug resistance mutations (DRMs) remains limited. We investigated virological factors associated to virological failure (VF) after switching to B/F/TAF in individuals with pre-existing DRMs. Methods: We performed a retrospective study in participants from the French regional prospective cohort ANRS-CO3-AquiVIH-NA. We included individuals treated with B/F/TAF between 2018/01/01 and 2021/12/31. Two groups were identified at B/F/TAF initiation: virologically suppressed (VS; Viral load (VL)<50cp/ml) and virologically unsuppressed (VU; VL>50 cp/mL). DRMs prior to B/F/TAF initiation were identified using cumulative genotypic resistance tests (GRT) according to the current ANRS algorithm. Factors associated with VF, defined as either two consecutive VL>50 cp/mL or a single VL>1000 cp/mL over 60 months of follow-up, were analyzed using a Cox proportional hazards model and survival curves. Results: Among the 636 participants with available GRT results, 82.7% were VS at B/F/TAF initiation. In the VU group, median [min; max] VL was 222 cp/ ml [51-2,574,903 cp/mL] at baseline. DRMs to at least one component of B/F/ TAF were present for 23.1% of participants (20.9% in VS and 33.6% in VU), with the M184I/V mutation identified in 89.1% of cases (88.1% in VS and 91.9% in VU). The occurrence of VF differed between VS and VU groups with an increased risk of VF (HR 9.9 ; CI 95% 5.7-16.9) in VU, and between participants with pre-existing DRMs (20/147; 13.6%) and those without (35/489; 7.2%). In VS participants, VF rates were: 4.5% (5/110) and 4.1% (17/416) among those with and without pre-existing DRMs, respectively. In VU participants, VF rates were 40.5% (15/37) and 24.7% (18/73) among those with and without pre-existing DRMs, respectively. Conclusions: This study highlights the good effectiveness of B/F/TAF in real-world settings. Indeed, B/F/TAF maintained virological suppression in VS participants regardless of pre-existing DRMs. In VU participants, the risk of VF was significantly higher compared to VS participants. These findings suggest that close medical monitoring of VU individuals should always be applied, even in those initiating B/F/TAF. Achievement of Undetectable HIV RNA in the PROMISE-US Study in Subjects Viremic at Baseline Kaitlin Anstett 1 , Princy Kumar 2 , Charlotte-Paige M. Rolle 3 , Christina Harbison 4 , Namrata P. Shah 5 , Smitha Gudipati 6 , for the PROMISE-US Investigators 1 Theratechnologies, Inc, Montreal, Canada, 2 Georgetown University, Washington, DC, USA, 3 Orlando Immunology Center, Orlando, FL, USA, 4 Prism Health North Texas, Dallas, TX, USA, 5 Whitman-Walker Health, Washington, DC, USA, 6 Henry Ford Hospital, Detroit, MI, USA Background: It is estimated that there are over 1.2 million people with HIV (PWH) in the United States. Of these, ~1% are heavily treatment-experienced (HTE) with multidrug resistant (MDR) HIV infection. MDR HIV is found most often in PWH with extensive prior exposure to antiretrovirals (ARVs). For these underrepresented HTE patients with MDR HIV-1, it can be challenging to establish and maintain virologic control, due to fewer active ARVs available for constructing a fully suppressive regimen. The PROMISE-US registry is dedicated to evaluating the efficacy of regimens used in this specific, complex patient population struggling with high unmet needs in the real-world. Methods: PROMISE-US (ClinicalTrials.gov Identifier: NCT05388474) is a phase 4 multicenter, retrospective and prospective, observational, non-interventional registry study. The primary objective is to evaluate the long-term efficacy and durability of ibalizumab in combination with other ARVs by comparing the clinical outcomes of patients receiving ibalizumab treatment (Cohort 2; C2) vs. matched patients not receiving ibalizumab (Cohort 1; C1). This abstract reports a sub-analysis from the first interim analysis, focusing on subjects who were viremic (>50 RNA copies/mL) at baseline and for whom matching has not yet been performed.

Results: By 8-Nov-2023, a total of 112 subjects were enrolled; 70 in C1, 42 in C2. Of these, 27 subjects in C1 and 25 in C2 were viremic at baseline (39% and 57%, respectively; p =0.0279); 84% of subjects in C1 had CD4+ T-cell counts above 200 cells/mm 3 at baseline, compared to 50% of subjects in C2 ( p =0.0002). Table 1 describes the sub-population of viremic subjects in this study. Subjects in C2 had statistically significantly higher mean viral loads (1060 vs. 12101 copies/ mL; p =0.0424) and lower mean CD4 T-cells counts (417 vs. 259 cells/mm 3 , p =0.0386) compared to C1. However, similar rates of undetectability (<50 RNA copies/mL) are achieved in those on ibalizumab compared to subjects on non-ibalizumab containing regimens at 6 (50% for C1 vs. 47.3% for C2) and 12 months (42.9 for C1 vs. 42.1% for C2). Conclusions: Despite displaying characteristics indicative of more severe HIV disease, subjects on ibalizumab-containing regimens have similar measures of undetectability at 6 and 12 months in the PROMISE-US registry compared to controls without ibalizumab in their regimens. Limitations of this analysis include small sample size, and unmatched disease severity between the two treatment groups.

Poster Abstracts

698

Outcomes for Persons With Triple-Class Resistant HIV and a History of Virological Failure Suzanne M. Ingle 1 , Fabrice Bonnet 2 , Linda Wittkop 3 , Alexandra Calmy 4 , Ramon Teira 5 , Timothy Sterling 6 , Heidi M. Crane 7 , Christoph Stephan 8 , Marc van der Valk 9 , Janne Vehreschild 10 , Giota Touloumi 11 , M. John Gill 12 , Adam Trickey 1 , Jonathan A. C. Sterne 1 , Mojgan Hessamfar 2 , for the Antiretroviral Therapy Cohort Collaboration (ART-CC) 1 University of Bristol, Bristol, UK, 2 Bordeaux University Hospital, Bordeaux, France, 3 University of Bordeaux, Bordeaux, France, 4 University Hospitals of Geneva, Geneva, Switzerland, 5 Hospital Sierrallana, Torrelavega, Spain, 6 Vanderbilt University Medical Center, Nashville, TN, USA, 7 University of Washington, Seattle, WA, USA, 8 University Hospital Frankfurt, Frankfurt, Germany, 9 Stichting HIV Monitoring, Amsterdam, Netherlands, 10 University of Cologne, Cologne, Germany, 11 National and Kapodistrian University of Athens, Athens, Greece, 12 University of Calgary, Calgary, Canada Background: The ANRS 139 TRIO trial provided evidence for the safety and efficacy of an antiretroviral therapy (ART) regimen containing raltegravir (RAL), etravirine (ETR), and darunavir/ritonavir (DRV/r) (combination called TRIO) for heavily treatment-experienced (HTE) people with HIV (PWH) with multidrug-resistance. Due to improved options for treatment simplification with 2nd generation integrase inhibitors, questions remain on how HTE PWH are managed in real-life settings. However, data on long-term outcomes are lacking. Methods: The Antiretroviral Therapy Cohort Collaboration (ART-CC) combines European and North American cohort studies of PWH. Eligible adults had: prior viral failure (1 viral load>200cp/ml) on nonnucleoside reverse-transcriptase inhibitors (NNRTI)-containing ART; ≥3 primary protease inhibitor and nucleoside reverse transcriptase inhibitor (NRTI)-mutations; and ≤3 darunavir and NNRTI mutations. Included PWH switched to the TRIO regimen between 2007-18 without prior exposure to TRIO drugs, and with viral failure. We examined viral suppression (<50cp/ml) while on TRIO, AIDS/mortality after starting TRIO, simplification (defined as switching to a 1 or 2 drug regimen) post-TRIO in those virally suppressed, and viral failure after simplification. We used competing risks to estimate cumulative incidence of outcomes after TRIO. Results: Of 126 eligible PWH, 24% were female; median age was 46 years (Interquartile range [IQR]: 41-50). Median follow-up duration 7.9 years (IQR: 5.1-9.3): total follow-up time 859 years. By end of follow-up, 23 (18%) had died, 12 (10%) were still on TRIO and 91 (72%) had stopped TRIO. 20/91 had no record of a switch to another regimen, 31/91 switched to a simplified regimen and the remaining 40/91 stopped TRIO to switch to another ≥3-drug regimen. The 5-year cumulative incidence of competing outcomes following TRIO was: stop TRIO and start another regimen with ≥3 drugs 32%; simplify 15%; stop TRIO without switch 17%; died on TRIO 7% (see graph). The rate of first AIDS/death

697

CROI 2025 199