1. Hepatitis C Virus (HCV) Clearance After Treatment With Direct-Acting Antivirals in Human Immunodeficiency Virus (HIV)-HCV Coinfection Modulates Systemic Immune Activation and HIV Transcription on Antiretroviral Therapy
- Author
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Horacio Salomón, Yanina Alexandra Ghiglione, Patricia Patterson, Alejandro Czernikier, Alicia Sisto, María Florencia Quiroga, Natalia Laufer, Gabriela Turk, Alejandra Urioste, Ajantha Rhodes, María José Rolón, María Laura Polo, Sharon R Lewin, César Ariel Trifone, and Sonia Bakkour
- Subjects
0301 basic medicine ,CIENCIAS MÉDICAS Y DE LA SALUD ,Hepatitis C virus ,Human immunodeficiency virus (HIV) ,Inmunología ,medicine.disease_cause ,HIV reservoir ,immune activation ,purl.org/becyt/ford/1 [https] ,Ciencias Biológicas ,purl.org/becyt/ford/3.3 [https] ,03 medical and health sciences ,0302 clinical medicine ,Biología Celular, Microbiología ,Transcription (biology) ,HIV RESERVOIR ,Major Article ,medicine ,purl.org/becyt/ford/1.6 [https] ,business.industry ,direct antiviral agents ,Hcv clearance ,virus diseases ,purl.org/becyt/ford/3.1 [https] ,Hepatitis C ,medicine.disease ,Virology ,IMMUNE ACTIVATION ,Medicina Básica ,AcademicSubjects/MED00290 ,030104 developmental biology ,Infectious Diseases ,Oncology ,Hiv hcv coinfection ,Coinfection ,HEPATITIS C ,purl.org/becyt/ford/3 [https] ,030211 gastroenterology & hepatology ,hepatitis C ,business ,DIRECT ANTIVIRAL AGENTS ,Virología ,CIENCIAS NATURALES Y EXACTAS ,Immune activation - 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., This article addresses the immediate and long-term effects of direct-acting antiviral-mediated HCV clearance on the HIV reservoir dynamics and immune function, in a cohort of HIV/HCV-coinfected individuals under antiretroviral treatment.
- Published
- 2020