Abstract / Summary
The tumor necrosis factor superfamily (TNFSF) members regulate diverse cellular processes, yet their systemic profiles remain insufficiently characterized in persons living with HIV (PLHIV) with disseminated Kaposi sarcoma (DKS) caused by Kaposi’s sarcoma-associated herpesvirus (KSHV). Plasma levels of fifteen TNFSF/TNFRSF molecules were quantified in twenty participants with DKS/HIV enrolled in a randomized clinical trial. Samples were obtained at diagnosis (week 0) and follow-up at weeks of treatment W 4 , W 12 , W 24 , W 48 , and W 365 . Three control groups were included: ten HIV-negative (HIV-), ten PLHIV without an AIDS defining event diagnosis (HIV+/AIDS-), and twenty-four HIV+ with an AIDS-defining event without KSHV- (HIV+/AIDS+). At baseline, DKS/HIV showed higher TNFR1 and TNFR2 levels than the control groups ( p < 0.0001). The APRIL level was lower compared to HIV+AIDS+ ( p < 0.0001) and HIV+AIDS- ( p = 0.0190). An exploratory multivariate ROC analysis identified TNFR1, TNFR2, and APRIL as the combination with the highest discriminatory performance (AUC = 0.979) for distinguishing DKS/HIV patients from other groups, including HIV+/AIDS+ (significant predictive accuracy = 94.5%). Longitudinal analyses showed decreases in TNFR1 and BAFF at week 24 (W 24 ), ( p < 0.0001 and p = 0.0018, respectively) and decreases in TNFR2 beginning at week 12 ( p < 0.0001), with sustained reductions through week 48 ( p < 0.0001), and week 365 ( p < 0.0001). Mixed effects modeling indicated significant associations between follow-up time and changes in TNFR1, TNFR2, and BAFF. Multiple linear regression analysis demonstrated significant associations between follow-up time and changes in TNFR1, TNFR2, and BAFF. This study describes baseline differences and longitudinal patterns of TNFRSF/TNFSF molecules in DKS/HIV. TNFR1, TNFR2, and APRIL showed the strongest baseline differences, whereas TNFR1, TNFR2, and BAFF displayed consistent temporal variations throughout the follow-up period. These exploratory findings support further evaluation of TNFRSF/TNFSF members as candidate biomarkers indicative of disease dynamics in DKS over both short-term (48 weeks) and long-term (7 years) follow-up.