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Background/Aims: Spontaneous viral clearance of the chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-infected patients is a rare event. We aimed to identify the clinical, therapeutic, demographic, and laboratory features associated with spontaneous HCV clearance in 16 HIV-infected patients with chronic hepatitis C (CHC, the largest case series, to our knowledge). Methods: This case series study reports the findings from 16 HIV/HCV coinfected patients with CHC who experienced spontaneous clearance of HCV infection. Patients were monitored between 2000 and 2013 in the Infectious Diseases Outpatient Clinic at the Centro Hospitalar S. João, Porto, Portugal. Results: Apart from antiretroviral therapy (ART), all patients were also consuming other potential hepatotoxic drugs (e.g., alcohol, illicit drugs, methadone, and antituberculosis medication). In all but 1 of the 16 HIV-infected patients with CHC, viral remission was associated with a temporary suspension of the ART. All patients showed a sustained HCV viral clearance. Conclusion: A possible drug-induced liver injury and/or suspension of ART may, in some cases, contribute to increasing the chances of spontaneous HCV clearance in HIV-infected patients with CHC. [ABSTRACT FROM AUTHOR]