Direct-Acting Antivirals Quickly Eradicate Hepatitis C Virus From the Liver in People With Human Immunodeficiency Virus but Do Not Fully Reverse Immune Activation

Background. Hepatitis C virus (HCV) infects nearly one-fourth of people with human immunodeficiency virus (HIV). The role of direct-acting antivirals (DAAs) on immune activation in people with HIV (PWH) and HCV is poorly understood. Methods. We quantified plasma HCV RNA and CXCL10 in persons with HCV monoinfection versus HIV/HCV coinfection receiving sofosbuvir-velpatasvir. Single-cell laser capture microdissection was applied to liver biopsies obtained before and within 4-7 days of DAA initiation to estimate HCV clearance and changes in interferon-stimulated genes (ISGs). Results. We enrolled 10 people with chronic genotype 1a HCV: 5 were PWH with ART-suppressed viremia and CD4+ T cell counts >200 cells/mu L. First- and second-phase plasma HCV RNA kinetics were not different between groups. Median (min-max) proportions of infected hepatocytes at biopsy 1 were 0.06 (0.01-0.59) in HCV monoinfection and 0.21 (0.04-0.87) in HIV/HCV coinfection and did not differ. Participants had lower intracellular HCV RNA levels at biopsy 2. CXCL10 levels declined in both groups but were higher in coinfection than in monoinfection even at the end of treatment. The proportion of cells expressing ISGs diminished in monoinfection but increased in coinfection. Conclusions. Whereas DAAs rapidly cleared intrahepatic HCV in both groups, immune activation was slower to diminish in PWH. Residual immune activation in PWH warrants further exploration. Clinical Trials Registration. NCT02938013.