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Hepatitis C virus (HCV) infection may go undiagnosed and continue to present a source of community-acquired or transfusion-associated infection because of shortcomings in sensitivity, specificity, and reproducibility of serologic tests. This project was designed to longitudinally study persons who were HCV seropositive or were at risk for seroconversion to characterize the course of infection. Sequential serum samples obtained semiannually from 617 homosexual male volunteers were available for study from the Pittsburgh site of the Multicenter AIDS Cohort Study. Testing by anti-HCV enzyme immunoassay (EIA) was performed on baseline (1984 to 1985) and most-recent (censor date, August 1992) samples. Selected samples were also assayed for alanine aminotransferase and by recombinant immunoblot (RIBA II) and nested PCR. A total of 17 of 617 (2.8%) men were HCV seropositive at entry. Of the 600 seronegative men, 9 converted to HCV seropositive during the study interval. Parenteral sources of exposure could be identified in 6 of these 26 HCV-seropositive men. Four men were HCV seropositive at baseline and seronegative at their most recent visit. Of the 26 HCV-seropositive men, 12 were also seropositive for human immunodeficiency virus. EIA analysis of 298 longitudinal samples from the 26 men revealed three patterns of HCV seropositivity: persistent, intermittent, and rare. Nine men (35%) showed intermittent or rare seropositivity with periods of over 1 year between some seropositive samples. PCR was positive in 76% of the HCV EIA-positive and 84% of the RIBA-positive samples. Thus, a low but significant number of homosexual men were HCV seropositive with variable positivity over several years of follow-up. A portion of these men become HCV seronegative. Individuals who exhibit intermittent or rare seropositivity are a challenge to diagnosis.

Long-term serologic follow-up of hepatitis C virus-seropositive homosexual men