Hepatitis C Virus (HCV) Direct-Acting Antiviral Therapy in Persons With Human Immunodeficiency Virus–HCV Genotype 1 Coinfection Resulting in High Rate of Sustained Virologic Response and Variable in Normalization of Soluble Markers of Immune Activation

• Published in: The Journal of infectious diseases Vol. 222; no. 8; pp. 1334 - 1344
• Main Authors: Anthony, Donald D, Sulkowski, Mark S, Smeaton, Laura M, Damjanovska, Sofi, Shive, Carey L, Kowal, Corinne M, Cohen, Daniel E, Bhattacharya, Debika, Alston-Smith, Beverly L, Balagopal, Ashwin, Wyles, David L
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 15.10.2020
• Subjects: 2-Naphthylamine; Adult; Anilides - therapeutic use; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Antiretroviral therapy; Antiviral agents; Antiviral Agents - therapeutic use; Antiviral drugs; Biomarkers - blood; Body mass index; Carbamates - therapeutic use; CD14 antigen; CD163 antigen; Cirrhosis; Clinical trials; Coinfection - drug therapy; Coinfection - immunology; Cyclopropanes - therapeutic use; Cytokines; Drug therapy; Drug Therapy, Combination; Female; Genotype; Genotypes; Hepacivirus - drug effects; Hepatitis; Hepatitis C; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - immunology; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1 - drug effects; Human immunodeficiency virus; Humans; Immune response; Immunologic Factors - blood; Interferon; Interferon-inducible protein; Interleukin 18; Interleukin 6; IP-10 protein; Lactams, Macrocyclic - therapeutic use; Liver cirrhosis; Liver Cirrhosis - drug therapy; Liver Cirrhosis - immunology; Major and Brief Reports; Male; Middle Aged; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Proline - analogs & derivatives; Proline - therapeutic use; Proteinase inhibitors; Proteins; Ribavirin; Ribavirin - therapeutic use; Ritonavir; Ritonavir - therapeutic use; Sulfonamides - therapeutic use; Sustained Virologic Response; Uracil - analogs & derivatives; Uracil - therapeutic use; Valine; immunity; inflammation; human; hepatitis C; DAA therapy
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiaa254

Abstract Background Hepatitis C virus (HCV) direct-acting antivirals are highly effective. Less is known about changes in markers of immune activation in persons with human immunodeficiency virus (HIV) in whom a sustained virologic response (SVR) is achieved. Methods We conducted a nonrandomized clinical trial of 12 or 24 weeks of paritaprevir-ritonavir-ombitasvir plus dasabuvir (PrOD) with or without ribavirin in persons with HCV-1/HIV coinfection suppressed with antiretroviral therapy. Plasma HCV, soluble CD14 (sCD14), interferon-inducible protein 10, soluble CD163 (sCD163), interleukin 6 (IL-6), interleukin 18, monocyte chemoattractant protein (MCP-1), autotaxin (ATX), and Mac2-binding protein (Mac2BP) were measured over 48 weeks. Results Participants were treated with PrOD for 12 (n = 9) or 24 (n = 36) weeks; the SVR rate at 12 weeks was 93%. At baseline, cirrhosis was associated with higher ATX and MCP-1, female sex with higher ATX and IL-6, older age with higher Mac2BP, higher body mass index with higher ATX, and HIV-1 protease inhibitor use with higher sCD14 levels. In those with SVR, interferon-inducible protein 10, ATX, and Mac2BP levels declined by week 2, interleukin 18 levels declined by the end of treatment, sCD14 levels did not change, and sCD163, MCP-1, and IL-6 levels changed at a single time point. Conclusions During HIV/HCV coinfection, plasma immune activation marker heterogeneity is in part attributable to age, sex, cirrhosis, body mass index, and/or type of antiretroviral therapy. HCV treatment with paritaprevir-ritonavir-ombitasvir plus dasabuvir is highly effective and is associated with variable rate and magnitude of decline in markers of immune activation. Clinical Trials Registration NCT02194998. During human immunodeficiency virus/hepatitis C virus (HCV) coinfection heterogeneity in markers of immune activation is likely in part attributable to age, sex, cirrhosis, body mass index, and/or type of antiretroviral therapy. HCV treatment with direct-acting antiviral PrOD is highly effective and associated with variable decline in immune activation markers.