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The purpose of the study was to evaluate reinfection and superinfection during treatment for recent hepatitis C virus (HCV). The Australian Trial in Acute Hepatitis C (ATAHC) was a prospective study of the natural history and treatment of recent HCV. Reinfection and superinfection were defined by detection of infection with an HCV strain distinct from the primary strain (using reverse-transcription polymerase chain reaction [RT-PCR] and subtype-specific nested RT-PCR assays) in the setting of spontaneous or treatment-induced viral suppression (one HCV RNA 10 IU/mL from enrollment to week 12). Among 163 patients, 111 were treated, 79% (88 of 111) had treatment-induced viral suppression, and 60% (67 of 111) achieved sustained virological response. Following treatment-induced viral suppression, recurrence was observed in 19% (17 of 88), including 12 with relapse and five with reinfection (4.7 cases per 100 person-years [PY], 95% confidence interval [CI]: 1.9, 11.2). Among 52 untreated patients, 58% (30 of 52) had spontaneous viral suppression and recurrence was observed in 10% (3 of 30), including two with reinfection. Following reinfection, alanine aminotransferase (ALT) levels >1.5x the upper limit of normal were observed in 71% (5 of 7). Among 37 with persistence, superinfection was observed in 16% (3 of 19) of those treated and 17% (3 of 18) of those untreated. In adjusted analysis, reinfection/superinfection occurred more often in participants with poorer social functioning at enrollment and more often in those with ongoing injecting drug use (IDU). Conclusion: Reinfection and superinfection can occur during treatment of recent HCV and are associated with poor social functioning and ongoing IDU. ALT levels may be a useful clinical marker of reexposure.