CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Resistance associated mutations (RAMs) were detected for 14 of them (30.4%), including 8 with RAMs already documented in a previous GRTs before B/F/TAF initiation. Among the 6 participants without previous RAMs, M184I/V was the only selected mutation. An emergent integrase mutation (R263K) was detected for one individual after 9 months of B/F/TAF. He had an unsuppressed baseline viremia (273,000 cp/mL) and documented M184V + 2 TAMs (D67N T215I) in historical GRTs. After VF, B/F/TAF was maintained in 47/55 (85.5%) participants of whom 28/47 (59.6%) achieved viral suppression, 19/47 (40.4 %) remained unsuppressed; 1/55 (1.8%) was lost of FU, ART regimen was changed in 5/55 (9.1%), and 2/55 (3.6%) died. Conclusions: The low prevalence (8.6%) of VF confirmed the real-world effectiveness and robustness of B/F/TAF in this study. Emergence of resistance in case of VF occurred rarely (RAMs selected at VF for 6 participants: mostly M184I/V, only one R263K). Poor or inconsistent adherence may explain most of VF cases, as 59.6% of participants in VF achieved viral suppression post-VF with B/F/TAF. This emphasizes the importance of adherence counselling in improving outcomes. Shifting Paradigms: Doravirine's Potential in Treating Non-Group M HIV-1, the DORAVI-O study Boris Derman 1 , Jeanne Pfister 1 , Fanny Lermechain 1 , Caroline Goudin 1 , Jean Christophe Plantier 2 , Elodie Alessandri-Gradt 2 1 Rouen University Hospital, Rouen, France, 2 University of Rouen Normandy, Normandy, France Background: Non-group M HIV-1 (O, N, and P) are known as genetically divergent and mainly found in Cameroon. Due to the prevalent Y181C mutation in 75% of non-M strains, current treatment guidelines has not recommended the use of Non-Nucleoside Reverse Transcriptase Inhibitors. However, the specific resistance profile of Doravirine (DOR) challenges this recommendation. The DORAVI-O study aims to assess the phenotypic sensitivity of non-M HIV-1 clinical isolates to DOR and explore potential genotypic patterns associated with resistance. Methods: Twenty eight HIV-1 non-M clinical isolates (26 O, 1 N, 1 P) were tested. Two millions human mononuclear cells from healthy donors were infected with 100 TCID50 of viral supernatant for 2 h and exposed to 5 concentrations of DOR (0.1 to 1,000 nM) in quadruplicates at 37°C with 5% CO2 for 3 to 4 days. Viral RNA was extracted (EZ1 Qiagen) and analyzed by qRT-PCR to determine the inhibitory concentration 50 (IC50), maximum percentage inhibition (MPI) and Fold Change (FC). Sanger sequencing (CEQ8000 Beckman) of RT region was performed and sequences compared with the updated french ANRS resistance algorithm. Results: The DOR phenotype was identified in 34% yield on the whole panel, according to internal standardization procedures. Of the 28 exploitable phenotypes 3 isolates (2 O, 1 P) exhibited IC50s>100,000 nM and 4 HIV-1/O had IC50s between [1,000; 10,000 nM], with FC > 100. For the remaining 21 isolates (0 < FC < 50), the mean and median IC50s (+-SD) were 133 nM and 37.4 nM (+- 181 nM) respectively, with IC50s ranging from 0.204 nM to 597 nM. The mean and median MPI were 79.25% and 78.73% respectively. Resistant strains generally displayed lower MPIs, like RBF168, P isolate (MPI 34.4%; IC50 > 100,000 nM) but except for BCF008 (IC50 1260 nM; MPI 90.4%). Most of the panel was classified as DOR intermediate sensitivity (french ANRS algorithm) due to A98G (96%) and Y181C (75%). However, resistant strains (IC50s > 100,000 nM), showed conflicting genotypic interpretations: RBF168 was genotypically sensitive while BCF108 was considered resistant (A98G, Y181C, G190A, and H221Y pattern). Conclusions: The DORAVI-O study revealed a broad phenotypic sensitivities of non-M HIV-1 to DOR , despite the natural Y181C mutation. Phenotypic resistance was observed in 6O, 1P (25%) whereas only 1O isolate has resistance mutations to DOR, suggesting the potential existence of non-M virus specific genotypic pattern not covered by the french ANRS algorithm designed for M variants. Impact of Resistance to Antiretroviral Therapy Among Veterans With Human Immunodeficiency Virus S. Scott Sutton 1 , Joe Magagnoli 1 , Tammy Cummings 1 , Chase Williams 2 , Mary J. Christoph 2 , Cassidy Trom 2 , Woodie Zachry 2 , Michelle D'Antoni 2 , Uche Mordi 2 , Amy Weinberg 2 , James W. Hardin 1 1 University of South Carolina, Columbia, SC, USA, 2 Gilead Sciences, Inc, Foster City, CA, USA Background: Despite significant progress made in antiretroviral (ARV) therapy for human immunodeficiency virus-1 (HIV-1) treatment, one of the

major challenges facing the efficacy of ARV is drug resistance. The objective of this study was to evaluate clinical outcomes associated with resistance to ARV among people with HIV (PWH). Methods: This national retrospective cohort study was conducted using data from the United States Department of Veterans Affairs. The Veterans Affairs Informatics and Computing Infrastructure (VINCI) was utilized to obtain individual-level information of structured claims data on demographics, medical claims, and pharmacy dispensation. Study cohorts were created by resistance testing results (non-resistance cohort, those with any resistance associated mutation (RAM) and those with ≥1 major RAM). The resistance cohorts had ≥1 documented RAM in integrase, protease or reverse transcriptase genes as defined by the International Antiviral Society-USA. Results: A total of 7,746 veterans had an interpretable resistance test with 1,875 with no detectable resistance, 4,466 with ≥1 minor RAM detected and 1,405 patients having ≥1 major RAM, and. Median CD4 counts within 60 days of index were higher among those without RAMs (358 cells/mm3) compared with those with any RAM (294 cells/mm3) or major RAMs (285 cells/mm3). Opportunistic infections occurred during follow up for 3.8% of the non resistance cohort compared to 5.6% of those with ≥1 minor RAM (p=0.005) and 5.1% of those with major RAMs (p=0.07). The number of hospitalizations post index was also greater in both the resistance and major RAM cohorts compared to those without resistance (p<0.001 for both). Among veterans who did not have an active ARV prescription at the time of the resistance test and who then initiated ARV (n=3,522), those with no resistance were more likely to persist on therapy at one year compared to those with resistance, with differences being even more pronounced in those with major RAMs (Figure), both p<0.0001. Among those with resistance taking complete ARV regimen at index who switched therapies, veterans generally switched to INSTI- or PI-based regimens. Conclusions: HIV drug resistance was associated with a more complex patient profile in both clinical and therapy outcomes. Patients harboring major RAMs exhibited lower CD4 counts, more frequent hospitalizations, and reduced ARV persistence. Interventions to prevent resistance development may reduce patient complexity and burden.

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Population-Based Longitudinal Dynamics of HIV Drug Resistance During Dolutegravir Roll-Out in Uganda Michael A. Martin 1 , Steven J. Reynolds 2 , Brian Foley 3 , Fred Nalugoda 4 , Thomas C. Quinn 5 , Godfrey Kigozi 4 , Robert Ssekubugu 4 , Joseph Kagaayi 4 , Oliver Ratmann 6 , Christophe Fraser 7 , Ronald Galiwango 4 , David Bonsall 7 , M. Kate Grabowski 8 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 3 Los Alamos National Laboratory, Los Alamos, NM, USA, 4 Rakai Health Sciences Program, Kalisizo, Uganda, 5 The Johns Hopkins University, Baltimore, MD, USA, 6 Imperial College London, London, UK, 7 Oxford University, Oxford, UK, 8 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background: African countries have shifted to dolutegravir (DTG)-based first-line HIV treatment. However, population-based studies of resistance trends through DTG roll-out in sub-Saharan Africa are extremely limited. Methods: We analyzed data from the Rakai Community Cohort Study, an open population-based cohort, during five survey rounds between 2012 and 2022. Consenting people aged 15-49 years were interviewed and provided samples for HIV testing, viral load quantification, and virus deep-sequencing. Sequence data from viremic samples (≥1000 copies/mL) were used to predict intermediate/ high-level resistance and identify resistance mutations. The prevalence

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