CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

such, there is interest in using subcutaneous low-dose delivery, but data are lacking. We recently completed a trial to evaluate low dose (10 mg or ~1.4 mg/kg) intra-lesional nivolumab in 6 males with HIV on ART and 6 HIV- males for cutaneious Kaposi sarcoma (KS) and demonstrated that the drug was safe without major adverse effects or autoimmune complications. Treatment also led to partial remission in 2 participants without HIV. Here, we studied the longitudinal impact of intra-lesional nivolumab on systemic PD-1 expression, T cell cycling, virus-specific immune responses, and HIV reservoir size. Methods: High-dimensional spectral flow cytometry was used to assess circulating T cell phenotypes, PD1 expression/receptor occupancy, and HIV and HHV8-specific immune responses prior to nivolumab therapy, following the 2nd dose and 26 weeks after the last of a total of 4-8 injections. HIV-1 reservoirs were measured in participants with HIV. Results: The percentage of circulating CD4+ and CD8+ T cells expressing PD-1 decreased from 23.8% and 19.2%, respectively, prior to treatment, to 10.9% and 9.4% before the third intra-lesional nivolumab injection across all participants (all P<0.05) not including nivolumab-bound cells which accounted for ~5-10% of residual PD1+ T cells while on treatment. The frequency of PD-1 expressing lymphocytes returned to baseline level 26 weeks after the last injection. A significant increase in the frequency of Ki67+ (cell cycling) terminally differential CD8+ T cells was observed from baseline to on therapy (P=0.04) and trend which was observed across all other memory CD8+ T cell subsets (Fug 1). HIV serostatus did not impact PD-1 expression or T cell proliferation. The frequency of CD4+ and CD8+ central memory and effector phenotypes also significantly increased on therapy compared to baseline (all P<0.05). No changes in HIV-1 or HHV8-specific CD4+ or CD8+ T cell frequencies or in cell-associated HIV-1 DNA or RNA were observed prior to, during and after treatment. Conclusions: Low dose locally delivered nivolumab was safe and led to marked PD1 downregulation and increases in T cell cycling and memory expansion in participants with and without HIV while receiving treatment. Given these promising data, larger studies will be needed to assess the impact on HIV-1 persistence and virus-specific immune responses.

performed using a custom Agilent SureSelectXTHS2 library preparation and target enrichment kit, which captured whole exons of 76 genes commonly mutated in CH and hematologic malignancies. Germline variant filtering included consideration of variant allele frequency (VAF) and recurrent presence in reference noncancer populations. The 850 K MethylationEPIC v1 BeadChip was used to capture genome-wide methylation status. DNA methylation–based biological age acceleration was calculated using epigenetic clocks including Hovarth, PhenoAge, Frailty, epiTOC, and DunedinPACE (estimates pace of aging). Results: Seventeen men with HIV and KS with a median (med) age of 55 years (range: 52-67 years), med CD4 T cell count of 126 cells/µL and med HIV viral load <20 copies/ml were included. The med time from HIV diagnosis and KS diagnosis to CH analyses was 14.9 years and 1.8 years, respectively. CH was detected in 10 of 17 (59%) pts before KS-directed therapy; 6 pts (35%) harbored CH mutations with >2% VAF. Fourteen pts had data on CD4 T-cell count before KS-directed therapy; CH was detected in 43% of pts with low CD4 T cell counts (<200 cells/µl) as compared to 21% in pts with CD4 >200 cells/µl (p=0.60). The DunedinPACE epigenetic measure was significantly higher among pts with low CD4 T cell counts ( Figure 1 ). All 7 pts who had CH present at baseline and received KS-directed therapy had CH detectable after treatment initiation as well. There were no changes in the epigenetic clock measurements between the two treatment timepoints. Conclusions: Among older PWH and KS, there was a high prevalence of CH and evidence of an association between low CD4 T cell counts and pace of aging in this population.

Poster Abstracts

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Causes of Death Among Adults With HIV-Associated Kaposi Sarcoma in East Africa in the Treat All Era Hilda Muwando 1 , Helen Byakwaga 2 , Aggrey Semeere 1 , Miriam Laker-Oketta 1 , Jeffrey Martin 2 , Racheal A. Ayanga 1 , Samson Kiprono 3 , Elia J. Mmbaga 4 , Winnie Muyindike 5 , Charles Kasozi 6 , Pendo Ibrahim 4 , Celestine Lagat 3 , Bronia Mwiine 5 , Elyne Rotich 3 , Philippa K. Makanga 1 1 Infectious Diseases Institute, Kampala, Uganda, 2 University of California San Francisco, San Francisco, CA, USA, 3 Academic Model Providing Access to Healthcare, Eldoret, Kenya, 4 Muhimbili University of Health and Allied Sciences, Dar es Salaam, United Republic of Tanzania, 5 Mbarara University of Science and Technology, Mbarara, Uganda, 6 Masaka Regional Referral Hospital, Masaka, Uganda Background: In East Africa, one-year mortality following a diagnosis of HIV associated Kaposi sarcoma (KS) in the Treat All era was recently estimated, in a community-derived sample, to be 41%. To date, there is limited information on why these patients die. Understanding causes of death among adults diagnosed with KS might improve management and, hence, survival or suggest other strategies. Methods: We identified adults (age ≥ 18 years) who died after a new diagnosis of HIV-associated KS between October 2022 and June 2024 and who were receiving care at one of 5 clinical sites in Kenya, Tanzania and Uganda. KS was confirmed by histopathology except where lesions were unsafe for biopsy. Adjudication of each death was performed using information obtained, when possible, from review of medical records and interview of attending clinicians and next of kin. A contributing cause of death was defined as suspicion that the condition mechanistically/causally contributed to death as guided by Rothman’s sufficient component cause (“causal pie”) model. Certainty of contribution to death was defined as highly (95%-100% certainty), likely (80%-95%) or possibly (50%-80%). Results: Of 163 deaths that were adjudicated, 63% were men, the median (IQR) age was 36 (29-42) years, and duration from diagnosis to death was 4 (1-14) weeks. Many (40%) deaths occurred outside a health facility, and only 4% had

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High Prevalence of Clonal Hematopoiesis Among Older People With HIV and Kaposi Sarcoma Ramya Ramaswami 1 , Ryan M. Putney 2 , Yi-Han Tang 2 , Robert Yarchoan 1 , Kathryn Lurain 1 , Nancy Gillis 2 , Anna E. Coghill 2 1 National Institutes of Health, Bethesda, MD, USA, 2 Moffitt Cancer Center, Tampa, FL, USA Background: Clonal hematopoiesis (CH) is the presence of somatically mutated hemopoietic progenitor cells without overt signs of hematologic abnormalities. CH is an age-related phenomenon that is associated with increased mortality. High prevalence of CH has been separately described in cohorts of people with HIV (PWH) with varying CD4 T cell counts and in patients (pts) with cancer. In a recent cross-sectional analysis of PWH and solid organ cancer types, CH prevalence was 23%. We investigated the CH prevalence and methylation assessment among older PWH and Kaposi sarcoma (KS), a virus-associated malignancy, before and after KS-directed therapy. Methods: Peripheral blood DNA was extracted from pts samples and used for CH detection and epigenetic methylation assessment. CH detection was

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