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

mtPIrtv in Andalusian 2-2-2016

mtPIrtv in Andalusian 2-2-201

Baseline patients’ characteristics.

<p>Baseline patients’ characteristics.</p

Kaplan-Meier estimations of the efficacy as determined by on-treatment analysis applying different criteria for virological failure.

<p>Kaplan-Meier estimations of the efficacy as determined by on-treatment analysis applying different criteria for virological failure.</p

Percentages of detectable HIV-RNA determinations (red) according to virological behavior during the follow-up for ritonavir-boosted protease inhibitor monotherapy.

<p>Undetectable viremia (green).</p

Efficaccy rates.

<p>A) Efficacy rates according to the ritonavir-boosted protease inhibitor used by intention-to-treat and by on-treatment analyses. B) Virological efficacy rates according to virological failure (VF) defined as >200 copies/mL or C) >50 copies/mL or treatment change due to a single positive viremia, according to the presence or absence of previous VF on a non-boosted protease inhibitor- and/or ritonavir-boosted protease inhibitor-based regimen (PI/rtv). DRV/rtv, darunavir/ritonavir; LPV/rtv, lopinavir/ritonavir.</p