Quantitative antibody responses to structural (core) and nonstructural (NS3, NS4, and NS5) hepatitis C virus proteins among seroconverting injecting drug users: Impact of epitope variation and relationship to detection of HCV RNA in blood

To gain insight into the natural history of hepatitis C virus (HCV), 13 hum an immunodeficiency virus (HIV)-seronegative injecting drug users were stud ied who seroconverted for HCV as determined by third-generation enzyme-link ed immunosorbent assay, showed an ensuing antibody response to HCV, and wer e not treated with any antiviral drugs during follow-up. Subjects included 13 untreated HIV-negative individuals, of whom 5 (38.5%) apparently cleared HCV and were polymerase chain reaction (PCR)-negative in at least 3 consec utive samples, 3 (23.1%) showed transient viremia and were PCR-negative in 1 sample during the study period, and the other 5 (38.5%) showed persistent viremia. Viremia was determined longitudinally by reverse-transcription PC R (RT-PCR) and quantified by branched DNA (bDNA). HCV genotypes were determ ined on serial samples during follow-up. Quantitative antibody levels to co re, NS3, NS4, and NS5 were determined using the Chiron RIBA HCV-titering St rip Immunoblot Assay, which is based on HCV genotype 1. The antibody respon ses to core, NS3, NS4, and NS5 were erratic. In individuals infected with H CV genotype 1, significantly higher median antibody responses to core (P = .02) and to NS4 (P = .04) were found as compared with those infected with o ther genotypes, showing a significant impact of HCV genotype specificity of the assay. In groups infected with HCV genotype 1, significantly higher me dian NS3 antibody titers (2.61 relative intensity [RI] vs. 0.38 RI; P = .00 3) were found in the individuals with persistent viremia than in those with apparent resolution of HCV RNA in blood. In groups infected with genotypes other than genotype 1, significantly higher median NS3 antibody titers (0. 89 RI vs. 0.03 RI; P = .0004) and NS5 antibody titers (1.86 RI vs. 0.01 RI; P = .006) were found in the individuals with persistent viremia than in th ose with apparent resolution of HCV RNA in blood. Individuals with viral pe rsistence had higher HCV-RNA loads with higher antibody responses as compar ed with individuals with apparent viral clearance from blood. Apparent vira l clearance from blood was observed in an unexpectedly high percentage (38. 5%), associated with a significant decrease of antibodies to NS3, independe nt of HCV genotype, as compared with individuals with persistent viremia (P < .005). Apparent viral clearance from blood with gradual loss of antibodi es to various HCV proteins, independent of HCV genotype, was observed in 4 of the 5 individuals within approximately I year after HCV seroconversion, whereas 1 of these individuals apparently cleared the virus from blood, wit h complete seroreversion.