Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection

Abstract

Background: Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients.

Patients and methods: This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073) enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 μg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control.

Results: Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events.

Conclusions: No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy.

Trial registration: ClinicalTrials.gov NCT01529073.

Conflict of interest statement

Competing Interests: The authors of this manuscript have read the journal's policy and have the following competing interests: JAP reports having received consulting fees from GlaxoSmithKline, Bristol- Myers Squibb, Abbot, Gilead and Boehringer Ingelheim Pharmaceuticals, Janssen, VIIH and Pfizer. He has received research support from GlaxoSmithKline, Roche, Bristol-Myers Squibb, Schering-Plough, Abbot, Boehringer Ingelheim Pharmaceuticals, Janssen and Pfizer, lecture fees from GlaxoSmithKline, Roche, Abbot, Bristol-Myers Squibb, Boehringer Ingelheim, Schering-Plough Pharmaceuticals, Janssen, VIIV and Gilead, and payment for manuscript preparation from Bristol-Myers Squibb, Boehringer Ingelheim and Roche, and for development of educational presentations from Gilead. JM has been an investigator in clinical trials supported by Roche, Bristol-Myers Squibb and Abbott Pharmaceuticals. He has received lectures fees from Roche, Gilead, Boehringer Ingelheim and Bristol-Myers Squibb, and consulting fees from Boehringer Ingelheim, Bristol Myers-Squibb and Merck Sharp & Dome. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. CONSORT 2010 flow diagram.

Fig 2. Response to nitazoxanide plus pegylated interferon alpha 2b and ribavirin compared to pegylated interferon alpha 2b and ribavirin (historical control).

Null response: 10 HCV RNA decrease at week 12. Partial response: ≥2 log10 HCV RNA decrease at week 12 with detectable HCV RNA at week 24.