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Abstract
Background
Hepatitis C virus (HCV) coinfection among people with human immunodeficiency virus (HIV) might perturb immune function and HIV persistence. We aimed to evaluate the impact of HCV clearance with direct-acting antivirals (DAAs) on immune activation and HIV persistence in HIV/HCV-coinfected individuals on antiretroviral therapy (ART).
Methods
In a prospective observational study, ART-treated participants with HIV/HCV coinfection received sofosbuvir/daclatasvir ± ribavirin (n = 19). Blood samples were collected before DAA therapy, at the end of treatment, and 12 months after DAA termination (12MPT). T- and natural killer (NK)-cell phenotype, soluble plasma factors, cell-associated (CA)-HIV deoxyribonucleic acid (DNA) forms (total, integrated, 2LTR), CA-unspliced (US) and multiple-spliced ribonucleic acid (RNA), and plasma HIV RNA were evaluated.
Results
Hepatitis C virus clearance was associated with (1) a downmodulation of activation and exhaustion markers in CD4+, CD8+ T, and NK cells together with (2) decreased plasma levels of Interferon gamma-induced protein 10 (IP10), interleukin-8 (IL-8), soluble (s)CD163 and soluble intercellular adhesion molecule (sICAM). Cell-associated US HIV RNA was significantly higher at 12MPT compared to baseline, with no change in HIV DNA or plasma RNA.
Conclusions
Elimination of HCV in HIV/HCV-coinfected individuals alters immune function and the transcriptional activity of latently infected cells. This report provides insights into the effects of HCV coinfection in HIV persistence and regards coinfected subjects as a population in which HIV remission might prove to be more challenging.
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Details
1 CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Buenos Aires, Argentina
2 The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Victoria, Australia
3 Hospital General de Agudos “Dr. J. A. Fernández,” Unidad Enfermedades Infecciosas, Buenos Aires, Argentina
4 Fundación Huésped, Buenos Aires, Argentina
5 Vitalant Research Institute, San Francisco, California, USA
6 The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Victoria, Australia; Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Australia
7 CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Buenos Aires, Argentina; Hospital General de Agudos “Dr. J. A. Fernández,” Unidad Enfermedades Infecciosas, Buenos Aires, Argentina