AIDS 2012 Abstract - The addition of nitazoxanide to peginterferon alfa-2a and ribavirin does not significantly improve sustained virologic response in HCV treatment-naïve genotype 1 HIV-1/HCV co-infected subjects: results of ACTG 5269

WEAB0103 - Oral Abstract Session

The addition of nitazoxanide to peginterferon alfa-2a and ribavirin does not significantly improve sustained virologic response in HCV treatment-naïve genotype 1 HIV-1/HCV co-infected subjects: results of ACTG 5269

Presented by Anne F. Luetkemeyer (United States).

V. Amorosa^1,2, T. Umbleja³, V. Johnson^4,5, M. Kang³, A. Luetkemeyer⁶, M. Bardin⁷, D. Haas⁸, R. Chung⁹, S. Yesmin¹⁰, K. Coughlin¹¹, A. Martinez¹², M.B. Adams¹³, B. Alston-Smith¹², P. Tebas², M. Peters⁶

¹Philadelphia Veterans Affairs Medical Center, Medicine, Philadelphia, United States, ²University of Pennsylvania, Medicine, Philadelphia, United States, ³Harvard School of Public Health, Boston, United States, ⁴Birmingham VA Medical Center, Birmingham, United States, ⁵University of Alabama Birmingham, Medicine, Birmingham, United States, ⁶University of San Francisco, San Francisco, United States, ⁷Romark, Tampa, United States, ⁸Vanderbilt University, Nashvile, United States, ⁹Harvard Medical School, Boston, United States, ¹⁰ACTG Operations Center, Bethesda, United States, ¹¹Frontiers Science & Technology Research Foundation, Amherst, United States, ¹²DAIDS, NIAID, NIH, Bethesda, United States, ¹³University of Rochester, Rochester, United States

Background: HIV-1/HCV coinfected patients respond poorly to pegylated interferon(PEG-IFN) and weight-based ribavirin(WBR), with sustained virologic response(SVR) of 27% in genotype 1 HCV treatment-naïve subjects (ACTG 5178 results). Nitazoxanide(NTZ) plus PEG-IFN and WBR has demonstrated improved efficacy in HCV monoinfected subjects. We hypothesized that addition of NTZ to PEG-IFN/WBR would improve HCV virologic responses in HIV-1/HCV co-infected persons.
Methods: HIV-1/HCV genotype 1 co-infected subjects naïve to HCV treatment received 4-week lead-in of NTZ(1000mg/day) followed by 48 weeks of NTZ, PEG-IFN alfa-2a(180 µg/week) and WBR(1000-1200 mg/day). SVR was defined as undetectable serum HCV RNA(< 43 IU/mL 24 weeks following end of treatment; Roche TaqMan HCV, v1.0). SVR proportion was compared with historical control proportion from ACTG 5178, using one-sided Fisher's exact test. Early virologic response(EVR, ≥2-log₁₀ IU/mL decrease from entry), complete EVR(cEVR, undetectable serum HCV RNA) after 12 weeks triple therapy, and rapid virologic response(RVR, undetectable after 4 weeks triple therapy) were previously presented. IL28B rs12979860 genotyping was done by ABI TaqMan.
Results: 67 subjects enrolled: 78% male, 48% black, 31% white, 18% Hispanic, median age 50 years, median entry CD4⁺ T-cell count 452 cells/mm³ and HCV RNA 6.38 log₁₀IU/mL. 73% had undetectable HIV-1 RNA. SVR was achieved in 22 subjects(32.8%, 90% CI 23.4-43.5%) compared to 27.3% in A5178 (p=0.24). SVR proportion was 86% among those who achieved RVR(6 of 7),50% among those who achieved EVR(22 of 44), 77% among those who achieved cEVR (20 of 26) and 6% among those who did not achieve cEVR (2 of 35). In contrast to A5178, SVR did not differ across IL28B genotypes (N=62,See table). Adverse events attributable to NTZ included diarrhea and nausea.

	N		SVR proportion (95% CI)
	A5178	A5269	A5178	A5269
C/C	38	15	42% (26-59%)	33% (12-62%)
C/T	51	37	33% (21-48%)	30% (16-47%)
T/T	23	10	4% (0-22%)	30% (7-65%)

[SVR proportion by IL28B genotype]

Conclusions: In genotype 1 HCV treatment-naïve HIV-1/HCV co-infected subjects in this pilot study, the addition of NTZ to PEG-IFN/WBR did not significantly improve SVR compared to historical controls with PEG-IFN/WBR.