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

<div><p>Background</p><p>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.</p><p>Patients and Methods</p><p>This was an open-label, single arm, multicenter phase II pilot clinical trial (<a href="https://clinicaltrials.gov/ct2/show/NCT01529073?term=NCT01529073&rank=1" target="_blank">NCT01529073</a>) 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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01529073?term=NCT01529073&rank=1" target="_blank">NCT01529073</a></p></div

Adverse effects experienced by the study patients.

<p>Adverse effects experienced by the study patients.</p

CONSORT 2010 flow diagram.

<p>CONSORT 2010 flow diagram.</p

Proportion of patients who presented undetectable HCV RNA at the different treatment weeks (TW).

<p>(A) Proportion of patients with undetectable HCV RNA during therapy including peg-IFN plus RBV in combination with BOC. (B) Proportion of patients with undetectable HCV RNA during therapy including peg-IFN plus RBV in combination with TVR. Grey bars: Intention-to-treat analysis; black bars: on-treatment analysis. *TW8 data was available in 44 patients receiving BOC and 43 patients receiving TVR.</p

Hematological abnormalities observed among patients receiving BOC- or TVR-based triple therapy and actions taken.

<p>^*detailed hematological data was available for 85 patients receiving TVR and 43 subjects receiving BOC;</p><p>^±information available in 93 patients receiving TVR and 42 subjects receiving BOC.</p><p>Hematological abnormalities observed among patients receiving BOC- or TVR-based triple therapy and actions taken.</p

Univariate and multivariate analysis to identify factors associated with sustained virologic response 12 weeks after scheduled end of therapy (SVR12).

<p>AOR: adjusted odds ratio; CI: confidence interval; <i>IL28B</i>: interleukin 28B.</p><p>^±available in 100 patients receiving TVR and 42 subject receiving BOC;</p><p>^¶as referred to dual therapy with peg-IFN plus RBV.</p><p>Univariate and multivariate analysis to identify factors associated with sustained virologic response 12 weeks after scheduled end of therapy (SVR12).</p

Baseline characteristics of the patients treated with BOC or TVR.

<p>^*Median (interquartile range);</p><p>^±available in 100 patients receiving TVR and 42 subjects receiving BOC;</p><p>^#available in 93 patients receiving TVR and 41 subjects receiving BOC;</p><p>^¶available in 92 patients receiving TVR and 41 subjects receiving BOC;</p><p>^§as referred to dual therapy with peg-IFN plus RBV<b>.</b></p><p>Baseline characteristics of the patients treated with BOC or TVR.</p

Rate of discontinuations due to adverse events.

<p>Proportion of patients who permanently discontinued all therapy due to adverse events after stratifying for baseline platelet count and albumin concentration. Data was available in 46 patients.</p