CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

790

Kaposi Sarcoma in Relation to HIV Diagnosis: Which Comes First in East Africa in the Treat All Era? Racheal A. Ayanga 1 , Aggrey Semeere 1 , Linda Chemtai 2 , Micheal Kanyesigye 3 , Mathew Ssemakadde 4 , Hilda Muwando 1 , Zainab Illonga 5 , Emmanuel Ochola 6 , Charles Kasozi 4 , Winnie Muyindike 7 , Elia J. Mmbaga 5 , Samson Kiprono 2 , Miriam Laker-Oketta 1 , Jeffrey Martin 8 , Helen Byakwaga 1 1 Infectious Diseases Institute, Kampala, Uganda, 2 Academic Model Providing Access to Healthcare, Eldoret, Kenya, 3 Mbarara Regional Referral Hospital, Mbarara, Uganda, 4 Masaka Regional Referral Hospital, Masaka, Uganda, 5 Muhimbili University of Health and Allied Sciences, Dar es Salaam, United Republic of Tanzania, 6 St Mary's Hospital Lacor, Gulu, Uganda, 7 Mbarara University of Science and Technology, Mbarara, Uganda, 8 University of California San Francisco, San Francisco, CA, USA Background: In 2015, the WHO recommended initiation of ART in all persons living with HIV, regardless of CD4 count or clinical stage, the dawning of the “Treat All” era. The intention of “Treat All” is to detect and treat HIV infection in its earliest stages. At the most macroscopic level, “Treat All” has been successful in most resource-limited settings, diminishing all-cause death related to HIV. What is less understood is whether all individual severe HIV-related complications have benefitted equally. We investigated how one oncologic complication — Kaposi sarcoma (KS) — has fared by examining when it develops in relationship to diagnosis of HIV infection. Methods: We identified adults (aged ≥ 18 years) with a new diagnosis of KS made between October 2022 and June 2024 in both inpatient and outpatient settings at several sites in East Africa that offer free-of-charge skin biopsy services: Uganda (Infectious Diseases Institute, Masaka and Mbarara Regional Referral Hospitals, and St. Mary’s Hospital Lacor); Kenya (Academic Model Providing Access to Healthcare network); and Tanzania (Muhimbili Univ. of Health and Allied Sciences). KS was confirmed by histopathology except in those with lesions that were deemed unsafe to biopsy. We used interviewer administered questionnaires to collect data on HIV diagnosis and KS history. Using the date that patients reported to have first noticed KS lesions and the date they reported HIV diagnosis was made, we describe the timing of KS lesion development in relation to HIV diagnosis. Results: Among 501 adults with a new diagnosis of HIV-related KS, 67% were men and the median (IQR) age was 36 (30-42) years. Median monthly household income was <$100 US. Among 482 patients with evaluable dates, 50% first noticed KS lesions ≥ one month prior to HIV diagnosis, 13% noticed lesions within ± 1 month of HIV diagnosis (the exact sequence could not be determined), and 37% noticed lesions ≥ 1 month after HIV diagnosis Conclusions: Amongst adults with newly diagnosed KS in East Africa in the ‘Treat all’ era, half developed KS prior to the health care system’s diagnosis of HIV infection. This indicates a need to improve HIV screening strategies in order to have HIV diagnosis made earlier, thus preventing progression to KS. The large proportion of patients developing KS after HIV diagnosis represents another research priority — why is this occurring and how can it be prevented?

KS can occur alone or with MCD or KICS. Liposomal doxorubicin (DOX) and pomalidomide (POM) are FDA-approved therapies for KS alone. A phase I/II study combining POM/DOX identified varying KS response rates (RR) by group. In participants (pts) in Group 1 (G1: KS alone) the RR was 71%, in pts in Group 2 (G2: KS with MCD or KICS), the KS RR was 45%. Evaluating the immunologic response may further our understanding of the RR differences. Methods: 51 pts (49 PWH, G1- 37 pts, G2- 14 pts) were enrolled in the POM/ DOX study. Pts received intravenous DOX at 20 mg/m 2 on day 1 combined with oral POM once daily on days 1 to 21 of a 28-day cycle. After adjusting for quality control aspects, we analyzed T-cell subsets among 23 participants using flow cytometry of peripheral blood mononuclear cells (PBMCs) at baseline and cycle 1 day 28 (C1D28). We evaluated markers of T-cell activation (CD38 and HLA-DR), exhaustion (PD-1), and senescence (CD57). Wilcoxon rank sum and signed rank tests were used to analyze significant differences between groups and paired changes across time points for flow cytometry, respectively. Results: Among all pts, there was an increase from baseline to C1D28 in the percentage of CD4 T-cells (P=0.0004) and a decrease in the percentage of CD8 T-cells (P=0.0009). The percentage of PD-1 + CD4 T-cells and PD-1 + CD8 T-cells were higher at baseline in G2 than in G1 (P=0.01, P=0.007, respectively, Figure 1). Among the effector memory (CD45RO + CD27 - ) T-cell population, G2 had higher percentages of PD-1 + CD4 T-cells (P=0.03), CD38 + HLA-DR + CD4 T-cells (P=0.02), and CD38 + HLA-DR + CD8 T-cells (P=0.02) than G1 at baseline. Among the naïve (CD45RO - CD27 + ) T-cell population, G1 had higher levels of CD38 + HLA DR - CD4 T-cells (P=0.007) compared to G2. On assessing baseline to C1D28 changes between the groups, only the percentage of CD38 + HLADR - central memory (CM, CD45RO + CD27 + ) CD4 T-cells increased and CD38 - HLADR + CM CD4 T-cells decreased in G1 compared to G2 (P=0.05, P=0.02). Conclusions: Patients with KS and MCD or KICS had increased expression of exhaustion markers on their effector memory CD4 and CD8 T-cell subsets. Thus, phenotypic differences at baseline in T-cells may inform differences observed in treatment response by group.

Poster Abstracts

791

Immunologic Responses to Pomalidomide and Liposomal Doxorubicin for Kaposi Sarcoma Treatment Matthew Witterholt 1 , Romin Roshan 2 , Kathryn Lurain 3 , Anaida Widell 1 , Irene Ekwede 1 , James Glassbrook 1 , Ralph Mangusan 1 , Thomas Uldrick 1 , Laurie Krug 3 , Denise Whitby 2 , Robert Yarchoan 3 , Ramya Ramaswami 3 1 National Cancer Institute, Bethesda, MD, USA, 2 AIDS and Cancer Virus Program, Frederick, MD, USA, 3 National Institutes of Health, Bethesda, MD, USA Background: Kaposi sarcoma herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), multicentric Castleman disease (MCD), and KSHV associated inflammatory cytokine syndrome (KICS). In people with HIV (PWH),

792

Impact of Low-Dose Intra-Lesional Nivolumab for Kaposi Sarcoma on T-Cell Proliferation and Function Chia-Ching Wang 1 , Amanda M. Buck 1 , Lilian Grimbert 1 , Cassandra Thanh 2 , Kieron Leslie 1 , Tyler-Marie Deveau 1 , Rebecca Hoh 1 , Michiko Ametani Shimoda 1 , Amelia N. Deitchman 1 , Steven G. Deeks 1 , Jeffrey Martin 1 , Paul Couey 2 , Toby Maurer 3 , Timothy J. Henrich 1 1 University of California San Francisco, San Francisco, CA, USA, 2 University of California San Diego Medical Center, La Jolla, CA, USA, 3 Indiana University Health, Indianapolis, IN, USA Background: PD1 antagonists are on the forefront of HIV curative strategies, but systemic treatment doses have led to limiting autoimmune toxicities. As

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