Highly Heterogeneous Kaposi Sarcoma-Associated Herpesvirus Oral Shedding Kinetics Among People With and Without Kaposi Sarcoma and Human Immunodeficiency Virus Coinfection.

Background: An improved understanding of oral Kaposi sarcoma-associated herpesvirus (KSHV) viral dynamics could provide insights into transmission risk and guide vaccine development.

Methods: We evaluated KSHV oral shedding dynamics in Ugandan adults stratified by Kaposi sarcoma (KS) and human immunodeficiency virus (HIV) status. Participants were followed for ≥4 weeks, with daily home oral swab collection to quantify KSHV using polymerase chain reaction. Shedding rates were defined by number of days with KSHV DNA detected divided by total days with swabs and compared by group using hurdle models.

Results: Two hundred ninety-five participants were enrolled; median age was 35 years (range, 18-71 years), and 134 (45%) were male. KSHV was detected more frequently among participants with KS (HIV positive [HIV⁺]/KS⁺, 56/76 [74%]; HIV negative [HIV^-]/KS⁺, 9/18 [50%]) than those without KS (HIV⁺/KS^-, 36/125 [29%]; HIV^-/KS^-, 16/76 [21%]); odds of shedding did not differ significantly by HIV status. Among participants with KSHV detected, shedding rates did not differ significantly by group. Median per-participant viral loads among positive samples were lowest in HIV⁺/KS⁺ (3.1 log₁₀ copies/mL) and HIV^-/KS⁺ (3.3 log₁₀ copies/mL) participants relative to HIV⁺/KS^- (3.8 log₁₀ copies/mL) and HIV^-/KS^- (4.0 log₁₀ copies/mL) participants. All groups had participants with low viral load intermittent shedding and participants with high viral load persistent shedding. Within each group, individual KSHV shedding rate positively correlated with median KSHV log₁₀ copies/mL, and episode duration positively correlated with peak viral load.

Conclusions: Oral KSHV shedding is highly heterogeneous across Ugandan adults with and without KS and HIV. Persistent shedding is associated with higher median viral loads regardless of HIV and KS status.