CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

samples from 23 ET and 14 LT participants who had been on ART a median of 68 months (45-101) was performed. We measured total HIV DNA using qPCR, and frequencies of intact and defective proviruses using the IPDA. Results: Thirty-eight (92.7%) participants were men. The median time from the estimated date of infection to ART initiation was 75 days (42-128) in the ET group and >180 days in the LT group. Pre-ART HIV viral load was higher in the ET group (p=0.035), but there were no significant differences in CD4+ and CD8+ counts, or CD4+/CD8+ ratio pre-ART (p>0.05). In the longitudinal analysis, all viral forms, included intact, declined over time in both cohorts. However, defective proviruses plateaued after 6-12 months of ART in LT participants, while continuous decay was observed in the ET group (p=0.01). Participants in the cross-sectional analysis maintained virological suppression for a median of 63 months (39-95) without significant differences between ET and LT (p>0.05). Total HIV DNA and defective proviral DNA levels were significantly higher in LT participants (Fig.1A). Although we did not observed differences in intact proviral DNA between groups (Fig.1A), the contribution of the intact form to the total pool of HIV-DNA was significantly higher in ET participants (Fig.1B). Conclusion: The intact HIV reservoir after ART remains similar between ET and LT individuals with comparable immunological status. Further research is necessary to determine the implications of these findings for HIV cure strategies.

of proviral HIV DNA integrated into CD4+ T-cells, but this population is rare. We evaluated how the time between seroconversion and ART initiation impacts HIV reservoir decay during up to 15 years of suppressive ART to clarify reservoir pathogenesis and inform future studies of strategies to achieve HIV remission. Methods: The U.S. Military HIV Natural History Study enrolls adult U.S. Department of Defense beneficiaries with HIV. We identified participants who achieved HIV RNA <400 copies/mL within 1 year of starting ART, maintained suppressive ART for at least 10 years, and had stored peripheral blood mononuclear cell (PBMC) specimens. PBMCs were analyzed using the intact proviral DNA assay (IPDA) to separately quantify intact and defective proviruses. We created linear spline models for intact HIV DNA, total HIV DNA, and proportion of intact HIV DNA based on time between estimated HIV seroconversion and ART initiation (<1 year vs. ≥1 year), with knots at 1, 4, 7, and 10 years on ART. Models were adjusted for age, race/ethnicity, CD4 count, and viral load at ART initiation. Correlations between intact and total HIV DNA were assessed using Spearman's rank correlation coefficient. Results: Of 83 participants, median age at ART initiation was 34.3 years (IQR: 29.2-41.5), 23 (27.7%) started ART within one year of estimated HIV acquisition (21 within 3-12 months), and 82 (98.8%) were male. The first ART regimen was NNRTI-based for 49 (59.0%). There were similar patterns of decay of intact HIV DNA (Figure), total HIV DNA, and proportion of intact HIV DNA between time to ART initiation groups. Intact HIV DNA was consistently lower in the earlier ART initiation group (1.13 vs. 1.54 log 10 copies/10 6 CD4+ T-cells at 10 years, p<0.05). Correlations between intact and total HIV DNA were strongly positive at all visits for both groups (range: 0.824-0.964; p<0.001). Conclusion: Earlier ART initiation was associated with lower levels of intact proviral DNA in PBMCs that persisted through 10-15 years of suppressive ART, at which point they were about 30% smaller in the early-treated group. Significant reservoir decay was observed through 10 years of ART. Future studies of curative interventions may consider enrolling participants who initiated ART within one year of year of estimated HIV acquisition, particularly those with a long history of suppressive ART.

Poster Abstracts

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Tumor Suppressor and Innate/Inflammatory Pathways are Associated With the HIV Reservoir Size German G Gornalusse 1 , Ashok K. Dwivedi 2 , Rebecca Hoh 2 , Jeffrey Martin 2 , Frederick Hecht 2 , Meei-Li Huang 1 , Julieta Reppetti 3 , Phuong M. Vo 1 , Claire M. Levy 1 , Pavitra Roychoudhury 1 , Keith R. Jerome 1 , Florian Hladik 1 , Timothy J. Henrich 2 , Steven G. Deeks 2 , Sulggi A. Lee 2 1 University of Washington, Seattle, WA, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 University of Buenos Aires, Buenos Aires, Argentina Background: The major barrier to an HIV cure is the HIV reservoir: latently infected cells that persist despite effective antiretroviral therapy (ART). Most prior studies of host genetic predictors of HIV control have focused on "elite controllers," rare individuals able to control virus in the absence of ART. However, there have been few genetic studies among ART-suppressed non controllers, who make up the majority of people with HIV (PWH). Methods: We performed a large cross-sectional study of 191 PWH on ART and measured host gene expression (RNA-seq) and HIV reservoir from peripheral blood CD4+ T cells. HIV reservoir was quantified as total DNA (tDNA), unspliced RNA (usRNA), and intact DNA. Results: After adjusting for nadir CD4+ count, timing of ART initiation, and genetic ancestry, we identified two host genes for which higher expression was significantly associated with smaller total DNA viral reservoir size, P3H3 and NBL1 , both known tumor suppressor genes. We then identified 17 host genes for which lower expression was associated with higher residual transcription (HIV usRNA). These included novel associations with membrane channel ( KCNJ2 , GJB2 ), inflammasome ( IL1A , CSF3 , TNFAIP5 , TNFAIP6 , TNFAIP9 , CXCL3 , CXCL10) , and innate immunity ( TLR7 ) genes (FDR-adjusted q<0.05). Gene set enrichment analyses further identified significant associations of HIV usRNA with TLR4/ microbial translocation (q=0.006), IL-1/NRLP3 inflammasome (q=0.008), and IL-10 (q=0.037) signaling. Protein validation assays using ELISA and multiplex cytokine assays supported these observed inverse host gene correlations, with P3H3, IL-10, and TNF-α protein associations achieving statistical significance (p<0.05). Of note plasma IL-10 was also significantly inversely associated with HIV DNA (p=0.016). HIV intact DNA was not associated with differential host gene expression, although this may have been due to a large number of undetectable values in our study.

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Intact HIV Remains Similar in Early- and Late-Treated Patients With Comparable Immunological Status Paula Suanzes 1 , Judith Grau-Expósito 2 , Jordi Navarro 1 , Joan Rey Cano 2 , Adrià Curran 1 , Joaquín Burgos 1 , Arnau Monforte 1 , Meritxell Genescà 2 , Vicenç Falcó 1 , María Buzón 2 1 Hospital Universitario de la Vall d’Hebron, Barcelona, Spain, 2 Vall d'Hebron Research Institute, Barcelona, Spain Background: The HIV reservoir stablished in the early stages of the acute HIV infection (AHI) and at the time of ART initiation is a major barrier to curing HIV. In this study, our objective was to assess the longitudinal impact of initiating ART during early HIV infection on the composition of the viral reservoir, in comparison to a cohort of individuals with similar immunological status treated during the chronic phase of the infection. Methods: The VHAHI cohort is an ongoing ambispective cohort (n=147) including patients with confirmed AHI in Barcelona (Suanzes et al, IJID, 2023). We included 25 participants from the VHAHI cohort that started ART within 180 days (early treated: ET), and 16 individuals with similar immunological status that started ART during the chronic phase of HIV infection (late treated: LT). We performed a longitudinal analysis after 0, 6, 12 and 36 months of ART in 13 ET and 7 LT participants. Moreover, a cross-sectional analysis using

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