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. Amorosa1,2, T. Umbleja3, V. Johnson4,5, 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 log10 IU/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.
[SVR proportion by IL28B genotype]
| ||N||SVR proportion (95% CI)|
|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%)|
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.
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