Indicators for Increased Likelihood of Epidemic Kaposi Sarcoma Progression After Antiretroviral Therapy Initiation

Kaposi sarcoma (KS) is a common malignancy for people living with HIV (PLWH), despite antiretroviral therapy (ART). Curiously, even with improved CD4⁺ T-cell counts and low viral loads following ART, some PLWH with KS may still experience KS progression or even death and require adjuvant chemotherapy to manage their KS. The factors associated with persistent or unresponsive KS after ART initiation remain poorly characterized, and biomarkers to identify patients at risk of KS progression are needed, particularly in resource-limited areas where access to chemotherapy is limited. Here we analyzed baseline KS tumor biopsies from PLWH with KS who required chemotherapy due to unresolved KS after ART initiation and those who did not require chemotherapy after ART initiation. By examining participant metadata and viral copy number for Kaposi sarcoma-associated herpesvirus (KSHV), HIV, cytomegalovirus, and Epstein-Barr virus and KSHV gene expression in the tumor biopsies prior to ART initiation, we identified a model of factors associated with KS progression after ART initiation, including biological sex, age, and the log ratio of KSHV/HIV copy number in the tumor. We believe that the ratio of KSHV/HIV may be linked to the cell types that each virus infects, and future work exploring the relationship between tumor and immune cells in the baseline tumors is planned. Innovation would be necessary to reduce costs and simplify the viral quantification assays, enabling the translation of these findings into routine clinical care, particularly in resource-limited settings.