Similar Viral and Immune Characteristics of Kaposi Sarcoma in ART-treated People Living With HIV and Older Patients With Classic Kaposi Sarcoma

Abstract

Background Re-emergence of HHV-8-induced Kaposi sarcoma (KS) in people living with HIV (PLWH) despite antiretroviral therapy (ART) poses a clinical challenge as these people already have favorable CD4 T-cell numbers and undetectable viral loads. We observed that clinical presentation in PLWH on ART resembled classic KS found in older HIV-uninfected patients and hypothesized that immunosenescence may thus play a role in occurrence of KS on ART. We compared viral and immune factors implicated in the development of KS in ART-treated PLWH (HIV KS) and HIV-uninfected classic KS patients (cKS), compared to controls without KS (HIV Control, cControls). Methods Plasma, PBMC and skin tissues were obtained from 11 HIV KS and 11 cKS patients, and two groups of age-matched controls. Results HIV KS participants were younger than cKS (53 vs 75yo). HHV-8 genotypes did not differ between groups. Despite the younger age and a lower CD4/CD8 ratio, activated, exhausted and senescent T-cells frequencies were similar between HIV KS and cKS. Anti-HHV-8 IgG levels were higher and circulating HHV-8 DNA lower in HIV KS compared cKS. Circulating PDGF-AA-BB and G-CSF were higher in HIV KS We observed similar levels of HHV-8 DNA and PD-1 expression in skin lesions from HIV KS and cKS patients. Conclusions Altogether, early immune senescence could be involved in the development of KS in ART-treated PLWH. Higher anti-HHV-8 IgG levels could be linked with lower circulating viral load. Such insights should help developing therapeutical strategies to prevent development and treat KS in PLWH on ART.