CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

factors SP3 and ETV3 were significantly decreased in participants with detectable versus undetectable monocyte CA-HIV RNA. Conclusion: In AHI, detectable monocyte HIV RNA is linked to notable transcriptional dysregulation, potentially impacting long-term myeloid cell programming and CNS outcomes. Identifying individuals with a higher transcriptionally active HIV myeloid reservoir warrants further study to guide early myeloid targeted treatment strategies and prevention of inflammation.

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Reduced HIV RNA Transcription During Long-Term ART Is Associated With Increased Ki67+ CD8+ T-Cells Alan Wells 1 , Christophe Vanpouille 2 , Noah Gaitan 1 , Antoine Chaillon 1 , Stephen Rawlings 3 , Victor DeGruttola 1 , Xinlia Zhang 1 , Miranda Lynch 4 , Xin Tu 1 , Alan Landay 5 , Eileen P. Scully 6 , Jonathan Karn 7 , Sara Gianella Weibel 1 1 University of California San Diego, La Jolla, CA, USA, 2 National Institute of Child Health and Human Development, Bethesda, MD, USA, 3 Tufts University, Boston, MA, USA, 4 Hauptman-Woodward Medical Research Institute, Buffalo, NY, USA, 5 Rush University, Chicago, IL, USA, 6 The Johns Hopkins University, Baltimore, MD, USA, 7 Case Western Reserve University, Cleveland, OH, USA Background: Sex-based differences affect HIV infection and immune responses. We investigate longitudinal T cell phenotypes and their association to HIV reservoir in men and women during long term suppressive ART. Methods: From the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials, we identified 52 cisgender women and 29 age-matched men. Participants were between the ages of 40-53 at time of ART initiation and virally suppressed (<20cp/ml) throughout the entire study period (318 timepoints, median 4 per participant). At each timepoint we measured markers of activation (HLA-DR+CD38+), cytotoxicity (CD107a+), cycling (Ki67+), exhaustion (TIGIT+PD-1) on T cell memory subsets (central memory, effector memory, terminally differentiated) and cellular HIV DNA and RNA (by ddPCR). Immune cell trajectories were analyzed with a negative binomial generalized additive model. Association between immune cells and HIV reservoir measures were analyzed using a similar model with a gaussian distribution. All p-values were adjusted for multiple comparisons (FDR). Results: At baseline, median CD4+ T cells were 218 cells/uL for women and 238 for men. Median follow up was 106 months for women and 83 for men. As expected, total CD4+ T cells increased, whereas CD8+ T cells decreased over time (p<0.001). Overall, we found a significant decrease in cellular markers of cycling (Ki67+) and activation (CD38+HLA-DR+) across all memory subtypes in CD4+ and CD8+ T cells (p<0.001). Similarly, we found a significant decrease in cellular markers of exhaustion (TIGIT+PD-1+) in all CD4+ T cell subtypes (p<0.01) but not in CD8+ T cells. Markers of T cell cytotoxicity (CD107a+) remained elevated over time. We did not observe any significant sex-difference in T cell dynamics. Increased proportions of effector memory and terminally differentiated CD8+ T cells expressing Ki67 were associated with lower cellular HIV RNA (p=0.037), and lower HIV DNA (p=0.016). Conclusion: While markers of T cell activation and cycling keep decreasing, cytotoxic CD4+ and CD8+ T cells and exhausted CD8+ T cells remain elevated in people with HIV despite years-long HIV suppression, as a possible consequence of ongoing antigen exposure. In both sexes, increased Ki67+CD8+ T cells correlate with reduced cellular HIV RNA and DNA. Although women showed a slower decline in HIV reservoir than men in this cohort (PMID:34612493), we did not detect any sex-differences in T cell phenotypes, suggesting that deeper phenotypic analysis might be needed. HIV-2 Transcription in Blood CD4+ T-Cells Is Inhibited by Blocks to Elongation and Completion Adam Wedrychowski 1 , Julie Janssens 1 , Sun Jin Kim 1 , Gayatri N. Kadiyala 1 , Sushama Telwatte 2 , Stacey M. Gaudreau 3 , Susan Cu-Uvin 4 , Athe Tsibris 5 , Steven A. Yukl 1 1 San Francisco VA Medical Center, San Francisco, CA, USA, 2 The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia, 3 The Miriam Hospital, Providence, RI, USA, 4 Brown University, Providence, RI, USA, 5 Brigham and Women's Hospital, Boston, MA, USA Background: HIV-2 differs from HIV-1 in sequence, transmissibility, and pathogenicity. Both can establish a latent infection that prevents cure, but it is unclear if the mechanisms that inhibit viral expression are the same for both viruses. As with HIV-1, we hypothesized that HIV-2 expression may be inhibited by blocks to transcriptional elongation, completion, and splicing.

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Antiretroviral Therapy Within 2 Years of HIV Acquisition Is Associated With Fewer Viral Blips Trevor A Crowell 1 , Hsing-Chuan Hsieh 2 , Xun Wang 2 , Xiuping Chu 2 , Britt Gayle 3 , Catherine M. Berjohn 4 , Jason M. Blaylock 2 , Joseph M. Yabes 5 , Derek T. Larson 4 , Robert J. O'Connell 2 , Anuradha Ganesan 2 , Brian K. Agan 2 , for the Infectious Disease Clinical Research Program (IDCRP) HIV Working Group 1 US Military HIV Research Program, Silver Spring, MD, USA, 2 Uniformed Services University of the Health Sciences, Bethesda, MD, USA, 3 US Military HIV Research Program, Bethesda, MD, USA, 4 Naval Medical Center San Diego, San Diego, CA, USA, 5 Brooke Army Medical Center, San Antonio, TX, USA Background: Viral blips may represent bursts of HIV replication or clonal expansion from reservoirs. Antiretroviral therapy (ART) started within days of HIV acquisition may limit reservoirs, thereby decreasing blips, but is uncommon. We evaluated the impact of ART initiation within months to years after HIV acquisition on the occurrence of viral blips. Methods: The ongoing U.S. Military HIV Natural History Study enrolls adult U.S. Department of Defense beneficiaries with HIV. HIV RNA results and ART medications are extracted from centralized electronic medical records. These analyses included participants who had an estimated HIV seroconversion date (midpoint of documented negative and positive test dates), achieved viral suppression (VS) ≤400 copies/mL within 1 year after starting ART, and had at least 3 HIV RNA measurements after achieving VS. A blip was any HIV RNA 401-1000 copies/mL immediately preceded and followed by HIV RNA ≤400 copies/mL without a change in ART. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors potentially associated with the time from VS to first viral blip. Results: From January 1996 to December 2022, 1,413 participants on suppressive ART met inclusion criteria for these analyses. Their median age at HIV diagnosis was 29.2 years (interquartile range 24.9-35.4) and a majority were males (96.3%). Viral blips were observed in 88 (6.2%) participants. Of these, 68 (77.3%) had a single blip, 13 (14.8%) had two blips, four (4.5%) had three blips, and three (3.4%) had four blips. The overall incidence of blips was 1.2 blips per 100 person-years (95% CI 0.9-1.4) and blip incidence decreased over time (Panel A). ART initiation within 24 months of estimated HIV acquisition was associated with decreased hazard of viral blips as compared to ART initiation after more than 24 months (0-6 months HR 0.32 [95% CI 0.20-0.52]; 6-12 months HR 0.48 [95% CI 0.35-0.67]; 12-24 months HR 0.52 [95% CI 0.40-0.69]; controlling for age, sex, race, time-updated ART regimen, time-updated CD4, HIV RNA at ART initiation, ART adherence [proportion of days covered >90%], history of hepatitis B, and history of hepatitis C; unadjusted in Panel B). Conclusion: Participants who initiated ART within two years of HIV acquisition had lower hazard of blips. Further research to characterize the clinical implications of blips and how they relate to HIV reservoir dynamics is ongoing. HIV reservoir plasticity may extend beyond the period of acute HIV.

Poster Abstracts

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CROI 2024 121