Kaposi sarcoma in ART-treated PLWH and HIV-uninfected people: differences in viral and immune characteristics


BACKGROUND: The incidence of HHV-8-induced Kaposi sarcoma (KS) in people living with HIV (PLWH) has dramatically decreased with antiretroviral therapy (ART). However, emergence of KS in ART-treated PLWH with restored CD4 and sustained HIV control is reported, raising concerns on HHV-8 pathogenesis and optimal management.
METHODS: We compared ART-treated PLWH with KS (KS ART+) and HIV-uninfected patients with classic KS (KS HIV-). We assessed CD4 and CD8 counts, anti-HHV-8 IgGs, gut permeability (LPS/I-FABP/Reg3) and senescence plasmatic markers (GDF15/suPAR). In PBMCs and skin biopsies, HHV-8 viral loads were quantified by digital-droplet PCR and positive samples are currently sequenced by next-generation sequencing. In skin biopsies, cells were isolated and analyzed by flow cytometry.
RESULTS: 11 KS ART+ and 11 KS HIV- have been recruited. KS ART+ were younger than KS HIV- (53 vs 77 years, p<0.001). Despite similar CD4 counts, KS ART+ had higher CD8 counts (p=0.007) and lower CD4/CD8 ratios (p=0.03). Gut permeability markers were similar while GDF15 and suPAR plasmatic levels were higher in KS HIV- (p=0.01). In PBMCs, HHV-8 DNA was detected in 6/11 KS ART+ while only in 3/11 KS HIV-. Anti-HHV-8 IgG titers tended to be higher in KS ART+ than KS HIV- (p=0.07). In skin biopsies, HHV-8 DNA was detected in all participant and isolated CD4 and CD8 T-cells highly expressed PD1 (>50%) in both groups. Among KS ART+, 3 HHV-8 strains were classified as subtype C and one as subtype A. In KS HIV-, 2 HHV-8 strains were classified as subtype A, 2 as subtype C and one strain, found in an Inuit patient from Northern Canada, constitutes a newly identified variant.
CONCLUSIONS: ART-treated PLWH with KS exhibited younger age and higher CD8 counts compared to HIV-uninfected KS patients. HHV-8 control seems altered in KS ART+, with HHV-8 DNA more frequently detected in PBMCs despite higher anti-HHV-8 IgG titers. Although still ongoing, HHV-8 sequencing revealed a new HHV-8 variant in an Inuit participant. Finally, PD1 expression on lymphocytes suggests T-cell dysfunction in skin lesions, constituting a potential therapeutical target. Such insights will help reducing KS-induced stigma and developing therapeutical strategies.

Download the e-Poster (PDF)