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Clinical Trial
. 2013 Nov-Dec;14(6):274-83.
doi: 10.1310/hct1406-274.

Addition of nitazoxanide to PEG-IFN and ribavirin to improve HCV treatment response in HIV-1 and HCV genotype 1 coinfected persons naïve to HCV therapy: results of the ACTG A5269 trial

Valerianna K Amorosa  1 , Anne Luetkemeyer  2 , Minhee Kang  3 , Victoria A Johnson  4 , Triin Umbleja  3 , David W Haas  5 , Suria Yesmin  6 , Matthew C Bardin  7 , Ray T Chung  8 , Beverly Alston-Smith  9 , Pablo Tebas  10 , Marion G Peters  2
Affiliations
Clinical Trial

Addition of nitazoxanide to PEG-IFN and ribavirin to improve HCV treatment response in HIV-1 and HCV genotype 1 coinfected persons naïve to HCV therapy: results of the ACTG A5269 trial

Valerianna K Amorosa et al. HIV Clin Trials. 2013 Nov-Dec.

Abstract

Background: We hypothesized that nitazoxanide (NTZ) added to pegylated interferon alfa-2a (PEG-IFN) and weight-based ribavirin (WBR) would improve hepatitis C virus (HCV) virologic responses in HCV treatment-naïve HIV-1/HCV genotype 1 coinfected persons.

Methods: Prospective, single-arm study in which subjects received 4-week lead-in (NTZ 500 mg twice daily) followed by 48 weeks of NTZ, PEG-IFN, and WBR. We compared the HCV virologic responses of these subjects to historical controls from the completed ACTG study A5178 who received PEG-IFN and WBR and had similar subject characteristics. Primary endpoints were early virologic response and complete early virologic response (EVR and cEVR).

Results: Among 67 subjects (78% male; 48% Black; median age, 50 years), EVR was achieved in 65.7% (90% CI, 55.0%-75.3%), cEVR in 38.8% (28.8%-49.6%). and SVR in 32.8% (23.4%-43.5%). EVR was higher with NTZ (51.4% in A5178; P = .03), but the sustained virologic response (SVR) proportion was similar (27.3% in A5178; P = .24). In contrast to A5178, SVR was similar across IL28B genotypes. Overall, NTZ was safe and well-tolerated.

Conclusion: Whereas EVR proportion improved significantly in this pilot study, the addition of NTZ to PEG-IFN/WBR did not significantly improve SVR compared to historical controls. NTZ may be associated with an attenuation of the effect of IL28B on HCV treatment response.

Keywords: HIV; genotype 1; hepatitis C; nitazoxanide; pegylated interferon; ribavirin.

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Conflict of interest statement

Conflicts of interests: Valerianna Amorosa, Anne Luetkemeyer, Minhee Kang, Triin Umbleja, Suria Yesmin, and Beverly Alston-Smith: No conflicts to declare.

Figures

Figure 1
Figure 1
Proportion of subjects with virologic response in A5269 and A5178. *P values for A5269 in (A) are from one-sided Fisher exact test for comparison with A5178 results presented in (B). cEVR = complete early virologic response; EVR = early virologic response; RVR = rapid virologic response; SVR = sustained virologic response; W12R = week-12 response.
Figure 2
Figure 2
Number and percent of subjects achieving sustained viro-logic response (SVR) by IL28B rs12979860 genotype in A5269 and A5178. NTZ/PEG-IFN/WBR = nitazoxanide/pegylated interferon alfa-2a/weight-based ribavirin; PEG-IFN/WBR = pegylated interferon alfa-2a/weight-based ribavirin.
See this image and copyright information in PMC

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