CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

360

Signature of CD4 T Cells During Acute HIV-1 Infection Is Predictive of Disease Progression Dominic Paquin-Proulx 1 , Bonnie M. Slike 1 , Ningbo Jian 1 , Boonrat Tassaneetrithep 2 , Leigh-Anne Eller 3 , Gina Donofrio 1 , Matthew Creegan 1 , Sandhya Vasan 3 , Julie Ake 4 , Mary A. Marovich 4 , Nelson L. Michael 4 , Merlin L. Robb 3 , Michael A. Eller 1 , Shelly J. Krebs 4 , for the RV 217 Study Team 1 Henry M Jackson Foundation, Rockville, MD, USA, 2 Mahidol University, Bangkok, Thailand, 3 Henry M Jackson Foundation, Bethesda, MD, USA, 4 Walter Reed Army Institute of Research, Silver Spring, MD, USA Background: Immune activation, a hallmark of chronic HIV infection, is a major contributor of HIV pathogenesis, even in the context of viral suppression by anti retroviral therapy. The magnitude of immune activation during HIV infection is both established early and is more predictive of the rate of disease progression than plasma viral load. Elucidating the critical events in acute HIV infection (AHI) associated with disease progression will facilitate the design of new approaches to achieve HIV remission. Methods: To investigate the dynamics of inflammation and immune activation during AHI, we utilized samples from 17 Thai and 26 East African participants in the RV217 AHI study. We measured the levels of 26 soluble markers of inflammation inclusive of chemokines, cytokines, and markers of microbial translocation starting from pre-infection through AHI. We determined the dynamics of cellular immune activation by assessing CD4 and CD8 T cell activation during AHI using flow cytometry. The level and frequency of immune activation was used to predict a CD4 T cell count <350 using nonparametric rank-based testing, logistic regression, and cumulative incidence. The prediction capability of identified markers was also examined by Area under the Receiver Operating Characteristic (AURCO) curve. Results: The level of soluble and cellular markers of immune activation between East Africa and Thailand significantly differed between regions both before and during AHI. Similarly, variable signatures of immune activation were associated with peak and set point viral loads for each region. IP-10, IL-8 and IL-10 levels were associated with peak viral load in Africa but not in Thailand. Levels of IL-1 β pre-infection in Thailand, but not in East Africa, were inversely associated with peak and set point viral loads. Combining datasets, higher levels of CCR5 and CD38 expression on CD4 T cells at 4.5 weeks post 1st HIV RNA positive test (around set point viral load) were predictive of reaching a CD4 count <350 independently of region or viral load. Conclusion: Our results show that the frequency of CD4 T cells expressing CCR5 and CD38 at set point viral load is associated with faster disease progression independent of viral load. This suggests that CD4 T cells circulating with an activated phenotype associated with susceptibility to viral entry may be predictive of immune pathology. Distinct Plasma Protein Changes Precede Loss of Spontaneous HIV Control Nadira Vadaq 1 , Albert L. Groenendijk 2 , Jessica D. Santos 1 , Wilhelm A. Vos 1 , Marc Blaauw 1 , Louise E. van Eekeren 1 , Leo Joosten 1 , Vasiliki Matzaraki 1 , Jan van Lunzen 1 , Susan M. Schader 3 , Casper Rokx 2 , Annelies Verbon 2 , Mihai Netea 1 , Ferdinand Wit 4 , Andre J. van der Ven 1 1 Radboud University Medical Center, Nijmegen, Netherlands, 2 Erasmus University Medical Center, Rotterdam, Netherlands, 3 ViiV Healthcare, Research Triangle Park, NC, USA, 4 Stichting HIV Monitoring, Amsterdam, Netherlands Background: Understanding antiretroviral therapy (ART)-independent control of HIV is of paramount importance and central for HIV cure. Some people living with HIV spontaneous regulate viral replication without ART and are categorized into 'elite controllers' (EC, HIV-RNA <50 c/mL) and 'viremic controllers' (VC, HIV-RNA between 50-10,000 c/ml). EC or VC may eventually lose controller status (HIV-RNA >10,000 copies/mL) and become transient controllers (TC), in contrast to persistent controllers (PC). Exploring plasma protein profiles of controllers that transition to TC may discern the intricacies of HIV pathogenesis and may ultimately yield new treatment strategies. Our aim was to scrutinize

mortality. The biomarkers associated with increased odds of mortality differed by sex. These findings suggest that there may be distinct pathophysiologic mechanisms that account for the observed increased risk of death seen in female PWH that warrant further investigation.

359

Glycomic Markers of Biological Aging in Trans Women With HIV Versus Cis Men and Cis Women With HIV Leila B Giron 1 , Ana N. Hyatt 2 , Mohamed Elkaeid 1 , Paula Debroy 2 , David B. Hanna 3 , Igho Ofotokun 4 , Margaret A. Fischl 5 , Daniel Merenstein 6 , Sabina Haberlen 7 , Alan Landay 8 , Frank Palella 9 , Phyllis Tien 10 , Todd T. Brown 7 , Jordan E. Lake 2 , Mohamed Abdel-Mohsen 1 1 Wistar Institute, Philadelphia, PA, USA, 2 University of Texas at Houston, Houston, TX, USA, 3 Albert Einstein College of Medicine, Bronx, NY, USA, 4 Emory University, Atlanta, GA, USA, 5 University of Miami, Miami, FL, USA, 6 Georgetown University, Washington, DC, USA, 7 The Johns Hopkins University, Baltimore, MD, USA, 8 Rush University, Chicago, IL, USA, 9 Northwestern University, Chicago, IL, USA, 10 University of California San Francisco, San Francisco, CA, USA Background: The effects of gender-affirming hormonal therapies (GAHT) on systemic markers of inflammation and aging among transgender women with HIV (TWWH) who are virally suppressed by antiretroviral therapy (ART) are unknown. Methods: Plasma samples were collected from 22 transgender women with HIV (TWWH); all were on estrogen, 50% were on spironolactone/antiandrogen, and 32% having testosterone levels <50ng/dL. These samples were age (± 5 years), race/ethnicity, and body mass index category matched with samples from 20 cisgender men with HIV (CMWH) and 18 cisgender women with HIV (CWWH, 6 pre-menopausal and 12 post- menopausal). All participants were on ART and had viral load <50 copies/ml. We measured two categories of plasma based markers of aging: 1) 20 markers of inflammatory aging (based on PMID: 34888528) using multiplex cytokine arrays, and 2) 31 IgG glycomic markers of biological aging (based on PMID: 24325898) using capillary electrophoresis. Kruskal-Wallis tests and Spearman correlations were used for analyses, and false discovery rates (FDR) were calculated to correct for multiple comparisons. Results: While we observed no differences in levels of inflammation markers between TWWH and CMWH, there were significant differences in levels of several IgG glycomic markers of aging between the two groups. Notably, levels of several galactosylated glycans, which are linked to younger chronological and biological age, were higher in TWWH compared to CMWH (FDR<0.05; Fig. 1A). Conversely, several agalactosylated glycans, linked to older age, were lower in TWWH compared to CMWH (FDR<0.05; Fig. 1B). These effects were consistent among TWWH, regardless of whether they had testosterone suppression or not. The anti-aging glycomic profiles of TWWH resembled those of pre-menopausal CWWH, while the pro-aging profiles of CMWH resembled those of post menopausal CWWH. The anti-aging profile, enriched in TWWH, was correlated with lower levels of several inflammation markers, including CXCL9, TNFα, and IP10, while the pro-aging profile, lower in TWWH, was associated with higher inflammation, especially in TWWH. Conclusion: TWWH exhibit anti-aging glycomic profiles that resemble those of pre-menopausal CWWH. Longitudinal studies are needed to better understand the relationships between GAHT, biological aging, and the risk of developing age-associated diseases. Mechanistic investigation is also warranted to explore the potential impact of GAHT and sex hormones on aging processes. The figure, table, or graphic for this abstract has been removed.

Poster Abstracts

361

82

CROI 2024