deLIVER: Direct Acting Antiviral Effects on the Liver

Primary Objective: The primary objective is to estimate the 1-week change in the proportion of HCV-infected hepatocytes in participants with HCV monoinfection and HIV/HCV coinfection on therapy with two or three DAAs with different mechanisms of action using single cell laser microdissection (scLCM). Secondary Objectives: Estimate the change over the first week in plasma HCV RNA in subjects with HCV monoinfected and HIV/HCV coinfected participants on therapy with two or three DAAs Estimate the 1 week change in the amount of HCV RNA per infected hepatocyte using scLCM on liver biopsy specimens, obtained just prior to treatment initiation (pre-treatment), and after the first week of DAA therapy. Estimate the change in the proportion of HCV-infected hepatocytes that express interferon-stimulated genes (ISGs) within the first week of DAA therapy using scLCM. Measure the change in expression of ISGs in non-parenchymal intrahepatic immune cells (Kupffer cells, plasmacytoid dendritic cells) within the first week of DAA therapy using scLCM. Exploratory Objectives: Estimate the 1 week change in expression of ISGs from peripheral blood mononucleated cells (PBMCs) within the first week of DAA+ribavirin (RBV) therapy using scLCM. Compare sequence(s) of HCV protease, nonstructural protein 5A (NS5A), and nonstructural protein 5B (NS5B) depending on the peripheral sequence) of intrahepatic HCV RNA in single cells and bulk tissue, before and during week 1 of DAA+RBV therapy. Estimate the week 1 change in the sizes and numbers of HCV-infected clusters on DAA therapy to test whether clearance of HCV-infected hepatocytes occurs in spatially random patterns or within specific clusters.