AbstractBackground and AimsTreatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver‐related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study.MethodsWe included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver‐related mortality, as well as the yearly incidence of liver‐related events in persons with at least one documented positive HCV‐RNA.ResultsOf 14 652 participants under follow‐up, 2294 had at least one positive HCV‐RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient‐years (PY) to 1.1 per 100 PY, and incidence of liver‐related events decreased from 1.4/100 PY to 0.2/100 PY.ConclusionsThe introduction of DAA therapy was associated with a more than 10‐fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver‐related events declined substantially in persons living with HIV and hepatitis C.