Seroconversion for human herpesvirus 8 during HIV infection is highly predictive of Kaposi's sarcoma

Background: The finding of antibodies against human herpesvirus 8 (HHV-8) i s associated with the occurrence of Kaposi's sarcoma in persons infected wi th HIV. However, the predictive Value of HHV-8 antibodies for Kaposi's sarc oma in HIV infection is unknown. Methods: The Amsterdam Cohort Studies on HIV infection and AIDS started in 1984 for homosexual men and in 1985 for injecting drug users. Serum samples from 1459 homosexual men and 1167 drug users were tested for antibodies to recombinant HHV-8 lytic-phase capsid (ORF65) antigen and latent-phase nucl ear (ORF73) antigen. Individuals were retrospectively identified as HHV-8-p ositive oi HHV-8-negative at enrolment or HHV-8 seroconverter during the st udy. Kaposi's sarcoma-free survival time was compared between HIV-infected men who were positive for HHV-8 at enrolment and those who later seroconver ted for HHV-8. Hazard ratios were estimated for Kaposi's sat-coma, lymphoma , and opportunistic infection according to the HHV-8 serostatus. Results: The incidence of HHV-8 seroconversion among drugs users was 0.7 pe r 100 person-years based on 31 seroconversions, whereas an incidence of 3.6 was found among homosexual men based on 215 seroconversions. The hazard ra tio for Kaposi's sarcoma was 3.15 (95% CI: 1.89-5.25) in HIV-infected indiv iduals if HHV-8 antibodies were present either at enrolment or at HIV seroc onversion. In HIV-infected persons who later seroconverted to HHV-8, Kaposi 's sarcoma developed more rapidly: hazard ratio of 5.04 (95% CI: 2.94-8.64) , an additional risk of 1.60 (95% CI: 1.01-2.53; P = 0.04). Time-dependent adjustment for CD4(+) cell count and HIV RNA had no impact on the additiona l risk, although the CD4(+) cell count was an independent risk factor for K aposi's sarcoma. HHV-8 infection did not increase the risk of AIDS-related lymphoma or opportunistic infections. Conclusions: The incidence of HHV-8 infection is higher in homosexual men t han in drug users. The presence of HHV-8 antibodies in HIV-infected persons increases the risk of Kaposi's sarcoma. Among HIV-infected persons, those who subsequently seroconvert for HHV-8 are at highest risk. These results s trongly confirm the causal role of HHV-8 in Kaposi's sarcoma and emphasize the clinical relevance of HHV-8 seroconversion before and after the HIV inf ection. (C) 1998 Lippincott Williams & Wilkins.