Valerianna K Amorosa1, Anne Luetkemeyer2, Minhee Kang3, Victoria A Johnson4, Triin Umbleja3, David W Haas5, Suria Yesmin6, Matthew C Bardin7, Ray T Chung8, Beverly Alston-Smith9, Pablo Tebas10, Marion G Peters2. 1. Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. 2. University of California at San Francisco, San Francisco, California. 3. Harvard School of Public Health, Boston, Massachusetts. 4. Birmingham Veterans Affairs Medical Center, Birmingham, Alabama University of Alabama School of Medicine, Birmingham, Alabama. 5. Vanderbilt School of Medicine, Nashville, Tennessee. 6. ACTG Operations Center, Silver Spring, Maryland. 7. Romark Laboratories LC, Tampa, Florida. 8. Harvard Medical School, Boston, Massachsetts. 9. Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 10. University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
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.
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.
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