Kaposi sarcoma herpesvirus (KSHV) subtypes and impact on survival in 107 patients with Kaposi sarcoma and other KSHV-associated diseases.

Abstract

11532 Background: Kaposi sarcoma herpesvirus (KSHV, also known as human herpesvirus 8) is an oncogenic virus that causes Kaposi sarcoma (KS), one of the most prevalent cancers in people with HIV (PWH) worldwide. KSHV also causes primary effusion lymphoma (PEL), a non-Hodgkin lymphoma, a plasmablastic variant of multicentric Castleman disease (MCD), and KSHV-associated inflammatory cytokine syndrome (KICS). KSHV-associated diseases (KADs) can occur alone or concurrently. The major KSHV genetic subtypes A, A5, B, C, D, E and F, based on the K1 open reading frame (ORF), are distributed by global region of origin. A and C genotypes are seen in Europe and North America whereas B and A5 variants are observed in Africa; D, E and F genotypes were described in isolated populations. There are limited data on the association between KSHV subtypes and survival outcomes. Methods: We investigated the ORF K1 subtype, disease characteristics, and impact on survival outcomes in 107 patients (pts) with KADs treated at the HIV/AIDS Malignancy Branch in the United States from 2010-2024. KSHV-DNA was extracted from peripheral blood mononuclear cells (PBMCs), KSHV-positive tissues and body fluids, including effusions. Extracted DNA was tested for KSHV using a CLIA-certified qPCR assay. Samples identified as KSHV-positive by qPCR were sequenced using either next-generation sequencing (NGS) or Sanger sequencing. Results: The cohort consisted of predominantly men (94%) and 55% were Black. Ninety-seven percent of pts had HIV (median CD4 count of 216 cells/mm3 and median HIV viral load 189,590 copies/mL). The most common KAD was KS (92%) followed by PEL (36%), MCD (23%), and KICS (22%). However, 64% had more than one concurrent KAD – 20% had KS and PEL. At the time of analysis, 39 (36%) pts were deceased, 26 (24%) had a PEL diagnosis. Seventy-nine percent of pts were from North America, 11% from Latin America and 9% were from sub-Saharan Africa; KSHV genotypes were consistent with a patient’s geographic origin. Overall, the most common genotype was A (44%), 30% of pts with genotype A had KS alone and 30% had PEL+/-KS (Table). KSHV subtypes based on K1 did not impact survival outcomes (Global Log-rank P=0.9) overall. In 98 pts with KS with and without other KAD, KSHV subtypes did not affect survival but the presence of concurrent PEL as compared to MCD or KICS lead to worse survival in pts [Hazard Ratio: 7.9 (95% confidence interval: 3.4-18.2, P<0.0001)]. Conclusions: In this large cohort of pts with KS and other KAD, KSHV genotype was not associated with survival outcomes. Among pts with KS, concurrent KAD, such as PEL, led to poorer survival. This suggests that clinical manifestations rather than underlying viral variants impacted survival. KSHV genotype prevalence (%) by KAD. Overall % A44% A58% B11% C26% Dual infection 8% KS 30 50 17 29 0 MCD +/- KS 11 0 17 14 22 PEL +/- KS 30 25 42 21 22 KICS + KS 17 25 17 29 33 MCD+PEL+/- KS 13 0 8 7 22