CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: Cohort study on PWH on ART with ≥1 episode of LLV since 2014. LLV defined as ≥2 consecutive viral loads (VLs) between 50 and 199 copies/mL ≥30 days apart, following a previous VL <50 copies/mL. In case of multiple LLV episodes, only the first was considered. In case of multiple ART switch during LLV, only the first was considered. Follow-up accrued from first VL 50-199 copies/mL [baseline (BL)] to VS (≥1 VL <50 copies), virological failure [VF (≥2 consecutive VLs ≥200 or ≥1 VL ≥1000 copies/mL)], second ART switch or last available VL measurement. Cox regression model applied to assess predictors of VS; ART switch considered as time-dependent variable. Results: Among 6794 PWH in care, 451 (6.6%) developed LLV and were included in the analysis: at BL, 380 (84.3%) males assigned at birth, median age 52.6 (interquartile range 45.8-57.9) years, on ART since 14.2 (6.1-20.9) years, virosuppressed since 3.4 (1.3-8.2) years, CD4+/CD8+ 0.7 (0.4-1.0), 347 (76.9%) on a triple therapy, 296 (65.6%) on a high genetic barrier regimen (including bictegravir, dolutegravir, and/or a boosted PI). After a median follow-up of 0.8 (0.4-1.1) years, 366 (81.2%) individuals achieved VS [303/366 (82.8%) maintained stable VS for ≥2 VL determinations] and 16 (3.5%) had VF. ART was switched in 176 (39.0%) PWH after 0.3 (0.1-0.6) years [136/176 (77.3%) achieved VS (stable in 87.5% of them), 4/176 (2.3%) had VF]. Risk of VS was significantly higher after ART switch [unadjusted hazard ratio (uHR)=2.1, 95% confidence interval (95%CI)=1.7-2.6, p<0.001]. This result was confirmed in sensitivity analyses on PWH on high [uHR=2.3, 95%CI=1.7-3.0, p<0.001] or low [uHR=1.9, 95%CI=1.3-2.7, p=0.001] genetic barrier regimens. At multivariable analysis, a higher risk of VS was significantly associated with ART switch, pre-BL history of VF, and resistance to ≥2 drug classes (Table 1). According to RNA-based genotyping, resistance-associated mutations might have been selected during LLV in 7 (1.6%) PWH. Conclusions: Low-level viremia during ART has a non-negligible prevalence in PWH and could be responsible for the emergence of resistance-associated mutations. Switching ART seems to be beneficial in achieving virological suppression, even in the case of high genetic barrier regimens.

Methods: Eligibility criteria for the A5324 included PWH with plasma HIV RNA < 50 copies/mL, ART regimens without INSTI or MVC, and with NCI on NP screening. This analysis focused on samples collected at baseline and weeks 2, 4, and 12, after randomization. HIV-1 virological markers were measured by ddPCR from total PBMC: cell-associated DNA (CA-DNA), CA-RNA, CA-2LTR. Residual plasma HIV RNA was measured by a low copy assay (LoD of 7 copies/mL). Results: 168 participants (70% assigned male sex at birth; 64% non-White) were enrolled and randomized to dual placebo (n=58), DTG+placebo (n=57), or DTG+MVC (n=53). CA-DNA and CA-RNA were detectable at both baseline and 12 weeks in 97% and 77% of participants, respectively, and did not differ between arms in change over 12 weeks (Wilcoxon rank-sum, P values > 0.2). In contrast, HIV-1 CA-2LTR was only detectable at both baseline and 12 weeks in 49% of participants. CA-2LTR was less frequently detected post-baseline in the DTG+MVC arm (58.5%) compared to placebo (29.3%) or DTG+placebo (31.6%) (Figure, Chi-square; vs. DTG, P = 0.03; vs. placebo, P = 0.02). Conclusions: Unlike some prior studies of INSTI intensification, we did not observe an early increase in CA-2LTR with DTG intensification. Unexpectedly, DTG+MVC intensification appeared to decrease CA-2LTR detection without affecting other virologic measures. One limitation of this finding is that the DTG+MVC arm exhibited a lower percentage of CA-2LTR detectable at baseline, despite randomization (Figure). The reduction of CA-2LTR detection with DTG+MVC may indicate suppression of residual replication, but other mechanisms are possible like altered migration of CA-2LTR-postive CD4+ T cells.

Poster Abstracts

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Factors Affecting Long-Term Trends of Immunologic Markers After ART: Results From the START Trial Christos Thomadakis 1 , Giota Touloumi 1 , Birgit Grund 2 , Ab Babiker 3 , Irini Sereti 4 , Karen Rogstad 5 , Rocío Montejano Sanchez 6 , Thomas Benfield 7 , Claudia P. Cortes 8 , Simon Collins 9 , Anthony D. Kelleher 10 , Mauro Schechter 11 , for the INSIGHT START Study Group 1 National and Kapodistrian University of Athens, Athens, Greece, 2 University of Minnesota, Minneapolis, MN, USA, 3 University College London, London, UK, 4 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 5 Sheffield Teaching Hospitals, Sheffield, UK, 6 Hospital Universitario La Paz, Madrid, Spain, 7 University of Copenhagen, Copenhagen, Denmark, 8 University of Chile, Santiago, Chile, 9 HIV i-Base, London, UK, 10 University of New South Wales, Darlinghurst, Australia, 11 Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Background: The START trial randomized ART-naïve individuals with CD4 counts>500 cells/μL to immediate ART initiation (Immediate group) or deferring ART until CD4 declined to 350 cells/μL or AIDS development. In 2015, all participants were recommended to start ART; extended follow-up continued through 2021. We assessed long-term immunologic responses over 10 years (CD4 count, CD4%, CD4/CD8 ratio), and identified factors influencing immune recovery. Methods: Linear mixed models with natural splines were used to model trajectories of the 3 markers post-ART initiation, which were compared across 4 groups defined by timing and CD4 count at ART initiation: (1) Immediate group, (2) Deferred >500 cells/μL, (3) Deferred 351-500 cells/μL, (4) Deferred ≤350 cells/μL. Although these comparisons are not protected by randomization,

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Impact of Antiretroviral Therapy (ART) Intensification on HIV-1 Virologic Markers (ACTG 5324) Jonathan Reed 1 , Luke Hall 2 , Ashley McKhann 2 , Ginger Kwak 1 , Erin A. Goecker 1 , Huichao Chen 2 , Eric S. Daar 3 , Peter W. Hunt 4 , Christina M. Marra 1 , Qing Ma 5 , Gene D. Morse 5 , Robert W. Coombs 1 , Scott L. Letendre 6 , Serena Spudich 7 , Alexander L. Greninger 1 , for the ACTG A5324 Study Team 1 University of Washington, Seattle, WA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 University of California Los Angeles, Los Angeles, CA, USA, 4 University of California San Francisco, San Francisco, CA, USA, 5 University at Buffalo, Buffalo, NY, USA, 6 University of California San Diego, La Jolla, CA, USA, 7 Yale University, New Haven, CT, USA Background: The A5324 trial investigated intensification with dolutegravir (DTG) +/- maraviroc (MVC) on neuropsychological performance (NP) in persons with HIV (PWH) and neurocognitive impairment (NCI) on suppressive ART. Intensification with these drug classes does not reduce the reservoir size or residual viremia, but changes in other virological parameters have been observed. For example, intensification with integrase strand transfer inhibitors (INSTIs) may increase early (2-4 week) cell-associated 2-LTR circle (CA-2LTR). MVC intensification may also increase CA-2LTR as well as cell-associated unspliced RNA (CA-RNA). We investigated the impact of the first 12 weeks of intensification with DTG +/- MVC versus dual placebo on these virologic measures in the large randomized, double-blind, placebo-controlled A5324 study.

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