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

Abstract

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 4.07/100 person-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 104.05/100 000 person-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.

Figure 1.

A) Geographical distribution of KSHV prevalence. Local KSHV prevalence is shown. Bubble position indicates the county or city location of each study site (study sites are listed in Table 3S). Bubble size indicates the number of participants; hue indicates prevalence. Estimated proportion of MSM in each state by is indicated by increasingly saturated shades of grey. B) Crude Prevalence and incidence of KSHV infection. Unadjusted prevalence and incidence of KSHV infection stratified by baseline characteristics are shown. C) Crude KS incidence. Unadjusted incidence of KS stratified by baseline characteristics is shown. MW/S indicates Midwest and South; NE/W, Northeast and West. D). Survival functions. Kaplan-Meier survival estimates are plotted for patient with (red) and without (blue) KS. Dotted lines delimit 95% confidence bands.