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To identify the prognostic significance of hemophilia- and virus-related factors, the authors undertook a survival analysis among 644 human immunodeficiency virus (HIV)-infected subjects enrolled in the Multicenter Hemophilia Cohort Study between 1985 and 1993. Acquired immunodeficiency syndrome (AIDS) was the leading cause of death, followed by hemorrhage and hepatic disease. Adverse prognostic factors included older age and CD4-positive lymphocyte values below 14 percent either at entry (age-adjusted mortality rate ratio (RR) = 6.4, 95% confidence interval (CI) 3.4-12.1) or after entry (time-dependent RR = 4.2, 95% CI 2.6-6.7); indeterminate antibody responses to hepatitis C virus (RR = 3.0, 95% CI 1.8-5.0); and inhibitory antibodies to factor VIII concentrates (RR = 1.8, 95% CI 1.1-3.1). Indeterminate hepatitis C virus status was associated with mortality from hepatic disease but not with AIDS mortality. Factors that were not prognostic included duration of HIV infection, hepatitis B virus infection, and other hemophilia variables. These findings suggest that fatal liver disease among coinfected subjects with an indeterminate hepatitis C virus status is probably related to an insufficient humoral response secondary to HIV immune dysfunction and that the risk of death among HIV-infected subjects is best evaluated with age and duration of low CD4 percentage.