Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 28, 2015; 7(18): 2177-2183
Published online Aug 28, 2015. doi: 10.4254/wjh.v7.i18.2177
Virological response and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus coinfection
Alissa Naqvi, Valérie Giordanengo, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Aline Joulié, Pierre Marie Roger, Eric Rosenthal
Alissa Naqvi, Brigitte Dunais, Francine de Salvador-Guillouet, Isabelle Perbost, Jacques Durant, Pascal Pugliese, Pierre Marie Roger, Infectious Diseases Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France
Valérie Giordanengo, Virology Laboratory, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France
Aline Joulié, Eric Rosenthal, Internal Medicine Department, Archet Hospital, Centre Hospitalier Universitaire, 06200 Nice, France
Author contributions: Naqvi A, Dunais B and Rosenthal E designed the research study; Pugliese P and Joulié A extracted the data from the database; Naqvi A, Giordanengo V, Dunais B, Joulié A and Rosenthal E interpreted the final data analysis and wrote the report; all authors read and critically commented on the paper.
Institutional review board statement: No Ethics Committee approval was required. The data collected in the Nadis® database and details of the networking organization have been submitted to the French National Commission on Informatics and Rights (CNIL).
Informed consent statement: All patients provide written informed consent prior to the inclusion of their data in the Nadis® database.
Conflict-of-interest statement: Rosenthal E reported receiving honoraria for participation in advisory boards for Gilead Sciences Inc, Abbvie and travel grants from Abbvie, Bristol-Myers Squibb, Gilead Sciences Inc, Janssen and Merck. The remaining authors have no conflict of interest to declare in relationship with this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Eric Rosenthal, Professor, Internal Medicine Department, Archet Hospital, Centre Hospitalier Universitaire, 51 Route de Saint-Antoine, 06200 Nice, France. rosenthal.e@chu-nice.fr
Telephone: +33-4-92035861
Received: November 19, 2014
Peer-review started: November 20, 2014
First decision: December 12, 2014
Revised: March 17, 2015
Accepted: July 21, 2015
Article in press: July 23, 2015
Published online: August 28, 2015
Processing time: 282 Days and 20.2 Hours
Abstract

AIM: To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients in a real life setting.

METHODS: Patients with HCV genotype 1-HIV coinfection followed in Nice University Hospital internal medicine and infectious diseases departments who initiated treatment including pegylated interferon and ribavirin (PegIFN/RBV) + telaprevir or boceprevir, according to standard treatment protocols, between August 2011 and October 2013 entered this observational study. Patient data were extracted from an electronic database (Nadis®). Liver fibrosis was measured by elastometry (Fibroscan®) with the following cut-off values: F0-F1: < 7.1 kPa, F2: 7.1-9.5 kPa, F3: 9.5-14.5 kPa, F4: ≥ 14.5 kPa. The proportion of patients with sustained virological response (SVR) twelve weeks after completing treatment, frequency and type of adverse events, and NS3/4A protease inhibitor mutations were described.

RESULTS: Forty-one patients were included: 13 (31.7%) patients were HCV-treatment naïve, 22 (53.7%) had advanced liver fibrosis or cirrhosis (Fibroscan stage F3 and F4); none had decompensated cirrhosis or hepatocellular carcinoma; all were receiving antiretroviral treatment, consisting for most them (83%) in either a nucleoside reverse-transcriptase inhibitor/protease inhibitor or/integrase inhibitor combination; all patients had undetectable HIV-RNA. One patient was lost to follow-up. SVR was achieved by 52.5% of patients. Five patients experienced virological failure during treatment and four relapsed. Seven discontinued treatment due to adverse events. Main adverse events included severe anemia (88%) and rash (25%). NS3/4A protease mutations were analyzed at baseline and at the time of virological failure in the 9 patients experiencing non-response, breakthrough or relapse. No baseline resistance mutation could predict resistance to HCV protease inhibitor-based treatment.

CONCLUSION: Telaprevir and boceprevir retain their place among potential treatment strategies in HIV-HCV coinfected patients including those with advanced compensated liver disease and who failed previous PegIFN/RBV therapy.

Keywords: Telaprevir; Boceprevir; Hepatitis C virus-human immunodeficiency virus coinfection; Resistance mutations

Core tip: Data regarding treatment of hepatitis C virus (HCV) infection with triple combination regimen including interferon/ribavirin and a protease inhibitor (telaprevir or boceprevir) among difficult to treat human immunodeficiency virus (HIV)-HCV co-infected patients are lacking. Most of the patients included in this single-center observational study had already failed a previous dual treatment course and had severe liver fibrosis, one out of six being both cirrhotic and non-responder to prior therapy. More than one of two patients displayed sustained virological response, suggesting that in low-income countries, telaprevir and boceprevir may retain their place among potential treatment strategies in HIV-HCV coinfected patients.