Risk factors for HHV8 seropositivity and progression to Kaposi's sarcoma in a cohort of homosexual men, 1981-96

Background: Human herpevirus 8 (HHV8) has been associated with Kaposi's sarcoma (KS). We investigated risk factors for transmission of HHV8, seroconversion rates by calendar time, and disease progression by HHV8 serostatus in Danish homosexual men followed 1981-96. Methods: Antibodies to latent and structural (orf65) antigens were measured by immunofluorescence and ELISA/WB, respectively. Cross-sectional analyses were performed between HIV serostatus, behavioral variables and HHV8 serostatus based on data collected among 259 homosexual men in 1981. Through regular follow-up visits, we calculated the monthly hazard of seroconverting to HHV8 and the relative hazard of seroconverting according to current HIV status and lifestyle behaviors ascertained in 1981. Results: 21.1% of the men were HHV8 seropositive in 1981. The rate of seroconversion was highest between 1981-82 and declined steadily thereafter. In a multivariate analysis of the status at enrollment in 1981, HHV8 seropositivity was not associated with age but independently associated with number of receptive anal intercourses and sexual exposure to homosexual men from the United States. Risk of seroconversion in follow-up data was independently associated with a history of sexual exposure to homosexual men from the United States and current HIV-positive status. More than 5-years experience as homosexual was associated with an insignificantly 2.7-fold increased risk. All KS cases were HHV8 seropositive prior to KS diagnosis. Among HHV8 seropositive men, sexual behavior appeared to modify the risk of KS whereas amyl nitrite and age had no effect on the risk of KS development. Conclusions: HHV8 seroconversion precedes KS development and is sexually transmitted in homosexual men, probably by receptive anal intercourse. HHV8 appears to have been introduced as an emerging epidemic to Danish men via contact with the US homosexual milieu in the late 1970s and early 1980s. This epidemic of HHV8 is now declining. Amyl nitrite use and age had no effect on KS development among HHV8 seropositive men.