CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

AG virus sensitive to VRC01.23 and 10E8v4-5R+100cF. To test the ability of this virus to escape bNAb neutralization, ex vivo CD4+ T cells were infected in the presence of varying bNAb concentrations in duplicate. Cultures were maintained for 60 days with increasing suboptimal concentrations of bNAbs to induce escape. Replication kinetics were monitored by p24 every 3 days. Every 14 days, target cells were replenished and cultures were tested for genotypic and phenotypic measures of bNAb resistance. This was accomplished by single genome sequencing env genes and using the remaining supernatant to spinoculate new CD4+ cells to propagate the escape assay. The remaining infected cells were washed and replenished with bNAb-free media for virus production, which was then tested by neutralization assay for bNAb resistance. Results: Nine non-subtype B viruses were tested against 8 bNAbs, and we observed CD4bs bNAbs to have the greatest breadth, but less potency than V2-apex or V3 bNAbs. In our experiments with E01-0085.V2, complete neutralization resistance to both bNAbs was observed by day 56 of the assay, but sequence signatures begin by day 28. Fixed escape mutations were observed within the epitopes of both antibodies by day 42 and possible compensatory mutations were observed by day 56. Conclusions: Our data reveal escape from both bNAbs was achieved by single non-synonymous nucleotide changes. This in vitro bNAb escape assay will lead to a deeper understanding of viral escape to better inform the design of highly effective bNAb cocktails targeting multiple conserved sites.

(Table). There were 108 (72%) with RAMs to at least one major ARV class (NRTI, NNRTI, PI or INSTI) at baseline, of which 67 (45%) had 2-class resistance and 9 (6%) had 3-class resistance. One participant on B/F/TAF met criteria for VF at Week 48; baseline and at failure genotypes had no RAMs. In the PI/r group, 3 of 4 participants who met criteria for VF at Week 48 had successful genotyping, one with NRTI and NNRTI RAMs (D67D/G, M184V, K103S, P225H) and two with NNRTI but no NRTI RAMs (K103N; V179V/D). Conclusions: Switching virally suppressed adults with or without NRTI resistance from a second-line PI/r regimen to B/F/TAF was non-inferior to continuing a PI/r regimen. These results suggest it can be done without baseline or historical drug resistance testing in regions where INSTI resistance is uncommon.

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HIV-1 Drug Resistance Trends in the Era of Modern Antiretrovirals: 2018-2024 Ron M. Kagan 1 , John D. Baxter 2 , Taekkyun Kim 1 , Elizabeth M. Marlowe 1 1 Quest Diagnostics, San Clemente, CA, USA, 2 Cooper University Hospital, Camden, NJ, USA Background: Transmitted or acquired antiretroviral (ARV) drug resistance limits treatment options for people living with HIV-1 and may reduce the effectiveness of preexposure prophylaxis (PrEP). Novel treatment options with enhanced effectiveness and more convenient formulations have become available from 2016 to 2021. This study assessed the prevalence of plasma RNA and proviral DNA ARV drug resistance in the US from 2018 to 2024. Methods: We retrospectively analyzed plasma RNA (N>50,000) or proviral DNA (N>25,000) deidentified specimens submitted to a large reference laboratory for Sanger or next generation sequencing between January 2018 and May 2024. Specimens were limited to US patients aged 1-90 with complete genotypic results for the reverse transcriptase, protease and integrase genes. We analyzed the annual prevalence of drug resistance mutations (DRMs) with a Stanford HIV database score of ≥30 for nucleoside reverse transcriptase inhibitors (NRTI), nonnucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase strand transfer inhibitors (INSTI). Results: From 2018 to 2024, the prevalence of resistance declined for both RNA and DNA specimens (Figure 1; p<0.0001). Single-class NRTI and NNRTI and dual class NRTI+NNRTI resistance declined for both specimen types but was higher for DNA than RNA (NRTI+NNRTI: 6.1% to 3.5% [RNA] and 12.1% to 7.8% [DNA]). Doravirine and rilpivirine DRMs remained low, with respective 2024 prevalences of 2% (RNA) and 2.9% (DNA) and 6.3% (RNA) and 10.1% (DNA). While INSTI and dual-class NRTI+INSTI resistance also declined, the prevalence was higher for RNA than DNA. Cabotegravir DRM prevalence in 2024 was 3.8% (RNA) and 2.5% (DNA). Although low, prevalence of R263K increased over time in RNA and DNA. PI resistance remained below 3% for RNA and declined from 5.3% to 2.1% for DNA. Prevalence of triple-class resistance was <0.2% for RNA but slightly above 1% for DNA. Resistance prevalence did not differ by gender but was higher for patients in the 60-90 age group. Conclusions: Prevalence of NRTI and NNRTI resistance declined which is consistent with increased use of regimens with higher resistance barriers, improved tolerability, and more convenient dosing, resulting in better adherence. Prevalence of INSTI DRMs was low, supporting US guidelines for limiting INSTI resistance testing to cases of treatment failure, suspected transmitted resistance, or infection during INSTI-based PrEP.

Poster Abstracts

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High Prevalence of Baseline NRTI Resistance in PWH Switched From Second-Line PI/r to B/F/TAF Jean Bernard Marc 1 , Samuel Pierre 1 , Paul Sax 2 , Johnny Wu 3 , Sean E. Collins 4 , Emelyne Dumont 1 , Fabienne Homeus 1 , Santiago Avila Rios 5 , Claudia Garcia Morales 6 , Vanessa Rivera 1 , Dennis Israelski 4 , Bernard Liautaud 1 , Jean W. Pape 1 , Serena Koenig 2 , Patrice Severe 1 1 GHESKIO Center, Port-au-Prince, Haiti, 2 Brigham and Women's Hospital, Boston, MA, USA, 3 Analysis Group, Inc, Boston, MA, USA, 4 Gilead Sciences, Inc, Foster City, CA, USA, 5 Instituto Nacional de Enfermedades Infecciosas, Mexico City, Mexico, 6 Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico Background: Patients on PI/r-based regimens in resource-limited settings have high rates of NRTI resistance, but testing is rarely available. Methods: In this open-label prospective trial conducted at GHESKIO in Haiti, virologically suppressed adults on second-line PI/r-based ART were randomized to continue current regimen vs. switch to B/F/TAF. The primary endpoint was the proportion with HIV-1 RNA ³200 copies/mL at week 48 using the FDA snapshot algorithm. Proviral DNA genotype testing (GenoSure Archive, Monogram Biosciences) was performed on baseline samples for all participants randomized to B/F/TAF, HIV RNA genotyping was done for participants with virologic failure (VF), and results were interpreted using IAS-USA resistance mutations (RAMs) and Stanford HIVdb version 9.6. Results: Between October 2020 and April 2023, of 436 patients screened, 301 were randomized and treated (B/F/TAF: 153; PI/r: 148); median age 48 years (IQR 40, 56) and 173 (58%) were women. At enrollment, 180 (60%) were taking LPV/r and 121 (40%) ATV/r; 234 (78%) were taking TDF, 54 (18%) AZT, and 13 (4%) ABC; all were taking lamivudine or emtricitabine. At week 48, the proportion with HIV-1 RNA ³200 copies/mL was 0.7% (1/153) and 4.1% (6/148) in the B/F/ TAF and PI/r groups, respectively, 145 (95%) and 132 (89%), respectively had 48-week HIV-1 RNA <200 copies/mL. Of 153 participants randomized to B/F/ TAF, 149 had baseline proviral genotype results. NRTI RAMs were common; 76 (51%) had M184V/I conferring resistance to FTC, 3TC and ABC, 24 (16%) had K65R/E/N conferring resistance to TDF, and 21 (14%) had M184V/I + K65R/E/N

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