Epidemiology of Kaposi's sarcoma-associated herpesvirus in HIV-1-infected US persons in the era of combination antiretroviral therapy

Objective:To determine the effect of the introduction of combination antiretroviral treatment (cART) in the HIV-1-infected US population on the epidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV).Design, setting and participants:We investigated the epidemiology of KSHV in 5022 HIV-1-infected, antiretroviral-naive US persons participating in six AIDS Clinical Trials Group (ACTG)-randomized clinical trials, and followed in a long-term cohort study. We tested the first and last available sera of each participant for antibodies to KSHV K8.1 and ORF73.Main outcome measures:We studied prevalence and incidence of KSHV infection, incidence of Kaposi's sarcoma, and overall survival.Results:KSHV prevalence was 38.1% [95% confidence interval (CI) 36.8-39.5%]. Male sex, Caucasian race, age between 30 and 49 years, residence in north-eastern or western United States, and enrolment after 2001 were independently associated with prevalent infection. KSHV incidence was 4.07/100person-years (95% CI 3.70-4.47). Male sex, Caucasian race, age below 30, and enrolment after 2001 were associated with incident infection. CD4(+) cell count increase following cART was associated with lower risk. Kaposi's sarcoma incidence was 104.05/100000person-years (95% CI 71.17-146.89). Higher baseline CD4(+) cell count, but not increase in CD4(+) cell count after cART, was associated with lower hazard of Kaposi's sarcoma. Randomized assignment of protease inhibitors was not associated with better KSHV outcomes.Conclusions:HIV-1-infected individuals, in particular Caucasian men, remain at a significant risk for KSHV co-infection and Kaposi's sarcoma. Thus, optimal management of HIV-1 infection should continue to include vigilance for manifestations of KSHV co-infection, including Kaposi's sarcoma.Video abstract:https://vimeo.com/126172348