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To determine Kaposi's sarcoma (KS) risk related to timing of human immunodeficiency virus type 1 (HIV-1) and human herpesvirus type 8 (HHV-8) infections, stored longitudinal sera from 400 homosexual men with known dates of HIV-1 seroconversion (+/-4.5 months) were tested for HHV-8 antibody. Times from HHV-8 seroconversion to KS were compared for the 69 men who became infected with HHV-8 after acquiring HIV-1 to the 182 men who were HHV-8 seropositive before their HIV-1 infection. None developed KS before coinfection. HHV-8 seroconversion after HIV-1 infection increased the risk of KS (risk ratio, 2.55; 95% confidence interval, 1.06-6.10) compared with those infected with HHV-8 before HIV-1. The KS hazards in HHV-8-infected men increased by 60% (P&lt;.001) for each year of HIV-1 infection. Faster CD4 cell loss and higher HIV-1 RNA levels significantly predicted KS. The quicker development of KS in men acquiring HHV-8 after HIV-1 and its association with CD4 slope argues that KS is more likely if HHV-8 infection occurs in an immunocompromised person.

Interaction of Human Immunodeficiency Virus Type 1 and Human Herpesvirus Type 8 Infections on the Incidence of Kaposi's Sarcoma