CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

750

Baseline KSHV T-Cell Responses Are Associated With Pre-Treatment Clinical Presentation in KS Ralph Kamel 1 , Minhee Kang 2 , Carlee Moser 2 , Richard Ambinder 3 , Dirk Dittmer 4 , Lara Hosey 5 , Roy Matining 2 , Mina Hosseinipour 4 , Margaret Borok 6 , Thomas Campbell 7 , Susan E. Krown 8 , Bernard Macatangay 1 , Charles R. Rinaldo 1 , for A5263/AMC066 and A5264/AMC067 1 University of Pittsburgh, Pittsburgh, PA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 The Johns Hopkins University, Baltimore, MD, USA, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 DLH Corporation, Silver Spring, MD, USA, 6 University of Zimbabwe, Harare, Zimbabwe, 7 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 8 Memorial Sloan Kettering Cancer Center, New York, NY, USA Background: T cell immunity is important in controlling KS herpesvirus (KSHV) disease progression. We evaluated T cell responses to KSHV and associations with pre-treatment clinical characteristics and outcomes in 2 ACTG/AMC studies (A5263/AMC066; A5264/AMC067) of KS treatment in resource-limited settings. Methods: T cell ELISPOT responses (log 10 spot-forming units [SFU]/10 6 cells) to 2 latency (LANA, K12) and 2 lytic (gB and K8.1) KSHV and to HIV Gag peptides were measured from 49 advanced KS (A5263/AMC066) and 94 mild/moderate KS (A5264/AMC067) participants with samples. In A5264/AMC067, we also measured T cell PD-1 expression by flow cytometry. Wilcoxon rank-sum and Fisher's exact tests were used. Results: At entry, median age was 34; mostly male and black African. Median CD4 count was 250 and 190 cells/mm 3 , and median plasma HIV-1 RNA was 3.5 and 5.1 log 10 cps/mL in advanced and mild/moderate KS, respectively. Advanced KS participants with oral KS had lower baseline responses to K12 (median: 0.76 vs 2.30 log 10 SFU; p=0.042), K8.1 (0 vs 2.3 SFU; p=0.038), and LANA (2.15 vs 3.02 SFU; p=0.039) than those without. In mild/moderate KS, a higher proportion of participants without oral KS had positive response to LANA (65% vs. 19%; p=0.013). Advanced KS participants with Karnofsky scores (KPS) <90 had higher gB responses than those with KPS ≥90 (median: 2.55 vs 0 SFU; p=0.046). Similarly, in mild/moderate KS, a higher proportion of participants with KPS <90 had detectable responses to gB (63% vs. 21%; p=0.040). Despite strong responses to Gag, this response was not associated with oral KS or KPS. There was a trend for mild/moderate participants with screening T0 KS stage to respond to gB compared to those with T1 stage (54% vs 17%; p=0.056). Mild/ moderate participants with oral KS had a trend for higher %PD1+CD8+ T cells (median 18.45% vs 14.40%; p=0.074) than those without. At 12 weeks, a higher proportion of mild/moderate participants without early KS disease progression had a drop in %PD-1+CD4+ (74% vs 21% with early disease progression; p=0.002) and %PD-1+CD8+ T cells (89% vs 57%; p=0.042). KSHV T cell responses were not associated with clinical outcomes in either study. Conclusion: In advanced and mild/moderate KS, pre-treatment KSHV specific T cell responses were associated with several pre-treatment clinical characteristics. In mild/moderate KS, decreased T cell exhaustion was associated with less early KS disease progression. This supports T cell immunity's importance in controlling KS.

associated with both malignancy and cardiovascular disease in the non-HIV population. Clonal hematopoiesis has been described as infrequent in patients under 50 and becomes more prevalent in the aging population. Recent studies have demonstrated that PLWH have a higher rate of CH than people without HIV. We aimed to describe CH in a cohort of PLWH as the initial phase of an ongoing analysis to determine the prognostic implications of CH in PLWH. Methods: We used phenotype and whole exome sequencing data from patients recruited to the Mount Sinai BioMe Biobank. We identified 487 patients in the cohort who met criteria for HIV. CH was called by excluding any patient with a myeloid malignancy and by filtering for predefined myeloid CH mutations with variant allele frequency (VAF) ≥ 2%. Results: Out of 487 total patients with HIV, we identified 29 patients with HIV with 30 CH mutations. The median age of patients without CH was 49, while the median age of patients with CH was 57. 7 out of 29 of patients with CH were below the age of 50. In logistic regression analysis, age was significantly associated with presence of CH in the HIV population (p=0.006) while ancestry, smoking, and sex were not. The most common CH mutations in the cohort were DNMT3A (8/30) and TET2 (4/30). None of the patients had mutations in ASXL1. Median VAF was 8.4% (IQR 6.6 – 11.7%). Conclusion:Our findings show a seemingly young age distribution of patients with CH in our cohort of PLWH, though we have not yet compared our cohort to a non-HIV population. Distinct from previously reported findings that ASXL1 was the most commonly mutated gene, we did not identify any mutations in ASXL1 in our cohort. Instead, other common CH genes such as DNMT3A and TET2 represented the majority of mutations. Interestingly, smoking, a commonly implicated risk factor for CH, was not significantly associated with presence of CH in our cohort. Multivariable analyses are ongoing with plans to investigate CH in patients with HIV as a predictor of cardiovascular disease, malignancy, and death. Inflammatory Signatures Predict the Risk of Severe Non-AIDS Events, Especially Non-AIDS Cancers Javier Martínez-Sanz 1 , Claudio Díaz-García 2 , Elena Moreno 2 , Laura Martín Pedraza 1 , Laura Luna Garcia 1 , Juan Carlos López Bernaldo de Quirós 3 , Jose I. Bernardino 4 , Marta Montero 5 , Enrique Bernal 6 , Helena Albendin Iglesias 7 , Santiago Moreno 1 , Sergio Serrano-Villar 1 , for the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) 1 Hospital Ramón y Cajal, Madrid, Spain, 2 Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain, 3 Hospital General Universitario Gregorio Marañón, Madrid, Spain, 4 Hospital La Paz Institute for Health Research, Madrid, Spain, 5 Hospital Universitario La Fe, Valencia, Spain, 6 Hospital Universitario Reina Sofia, Murcia, Spain, 7 Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain Background: While elevated levels of inflammatory biomarkers in people with HIV (PWH) have consistently been linked to a higher risk of severe non-AIDS adverse events (SNAEs), their clinical significance and the relevant inflammatory pathways are not well-established. Methods: In this nested case-control study within the Spanish AIDS Research Cohort (CoRIS), from a pool of 18,573 PWH we selected 89 cases who experienced SNAEs after two years of ART (including cardiovascular events, non-AIDS-related cancers, or non-accidental deaths) and had available plasma at month 24 (±6) of suppressive ART. Cases were matched with 89 controls using propensity-score matching. Covariates included age, sex, risk factor for HIV transmission, AIDS history, geographical origin, year 2 CD4/CD8 ratio, baseline HIV RNA, ART regimen, total cholesterol and HDL cholesterol. We measured the expression of 368 inflammatory proteins in plasma using Olink Proteomics' Proximity Extension Assay and analyzed their functions in Metascape. We used Welch 2-sample t-tests at a confidence level of 0.95 for every protein for a given outcome and corrected for multiple testing by the Benjamini-Hochberg method. Results: We studied 178 PWH, median age 45 years, 25% women, 49% smokers, median CD4 nadir 208 cells/uL, median CD4 counts at year 2 469 cells/ uL. We found significant changes in the expression of inflammatory proteins before month 24 subsequently predicting SNAEs risk. In cases, 25 proteins were upregulated, and 8 were downregulated. The greatest size effect was found for CLIP2, SKAP2, DAPP1, MANF, with approximately two-fold increased expression in cases. A subanalysis on patients with cardiovascular events and non accidental deaths did not show significant differences in protein expression. In contrast, cases who experienced non-AIDS cancers showed a marked (near 3-fold) upregulation of 59 plasma proteins and downregulation of 2 proteins, being SKAP2, CLIP2, DAPP1 and MANF those more discriminant between groups. Functional analyses indicated that these proteins predicting SNAEs are involved

Poster Abstracts

752

751

Description of Clonal Hematopoiesis in a Hospital-Based Cohort of People Living With HIV Manasa Bhatta, Myvizhi Esai Selvan, Daniel I. Nathan, Nikolaos Spyrou, Zeynep

Gumus, Bridget Marcellino, Keith Sigel Icahn School of Medicine at Mt Sinai, New York, NY, USA

Background: In the antiretroviral therapy era, the population of people living with HIV (PLWH) is aging, with increased mortality from chronic diseases and non-AIDS defining cancers. Similarly, clonal hematopoiesis (CH) has been

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