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.

Details

Title
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
Ghiglione, Yanina 1 ; Polo, María Laura 1 ; Urioste, Alejandra 1 ; Rhodes, Ajantha 2 ; Czernikier, Alejandro 1 ; Trifone, César 1 ; Quiroga, María Florencia 1 ; Sisto, Alicia 3 ; Patterson, Patricia 4 ; Salomón, Horacio 1 ; Rolón, María José 3 ; Bakkour, Sonia 5 ; Lewin, Sharon R 6 ; Turk, Gabriela 1 ; Laufer, Natalia 7 

 CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Buenos Aires, Argentina 
 The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Victoria, Australia 
 Hospital General de Agudos “Dr. J. A. Fernández,” Unidad Enfermedades Infecciosas, Buenos Aires, Argentina 
 Fundación Huésped, Buenos Aires, Argentina 
 Vitalant Research Institute, San Francisco, California, USA 
 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 
 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 
Publication year
2020
Publication date
May 2020
Publisher
Oxford University Press
e-ISSN
23288957
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3170979600
Copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.