11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th:Abstract No. 110

R Chung¹, J Andersen², P Volberding³, G Robbins¹, T Liu², K Sherman⁴, M Peters³, M Koziel⁵, B Alston⁶, D Colquhoun⁷, T Nevin⁸, G Harb⁹, C van der Horst¹⁰, and AIDS Clinical Trials Group A5071 Study Team
¹Mass Gen. Hosp., Boston, MA, USA; ²Statistical and Data Analysis Ctr. (SDAC), Harvard Sch. of Publ. Hlth., Boston, MA, USA; ³Univ. of California, San Francisco, USA; ⁴Univ. of Cincinnati, OH, USA; ⁵Beth Israel Deaconess Hosp., Boston, MA, USA; ⁶DAIDS, NIAID, NIH, DHHS, Bethesda, MD, USA; ⁷DMC, FSTRF, Buffalo, NY, USA; ⁸Social and Sci. Systems, Inc., Rockville, MD, USA; ⁹Roche Labs., Nutley, NJ, USA; and ¹⁰Univ. of North Carolina at Chapel Hill, USA

BACKGROUND: Chronic hepatitis C virus (HCV) is a major morbidity in persons infected with HIV. Treatment of HCV in HIV co-infection has been associated with poor responses and frequent intolerability. We conducted the first randomized trial of the efficacy and safety of peginterferon plus ribavirin vs interferon plus ribavirin for treatment of chronic HCV in HIV co-infection.

METHODS: A total of 133 subjects were randomized to 180 µg of peginterferon--2a (PEG) weekly for 48 weeks or to interferon--2a (IFN) 6 MIU 3 times weekly for 12 weeks followed by 3 MIU 3 times weekly to complete 48 weeks. Both arms received ribavirin in a dose-escalation schedule from 600 mg/d to 1000 mg/d. At week 24, subjects who failed to achieve HCV clearance underwent liver biopsy, and medications were continued for virologic response (HCV RNA < 60 IU/mL) or histologic response (HR: >2 point drop in hepatic activity index).

RESULTS: As previously reported (CROI 2002, LB15), week 24 VR was 44% with PEG/ribivirin vs 15% with IFN/R (p = 0.0003). End of treatment virologic response was 41% with PEG/ribivirin vs 12% with IFN/ribivirin (p = 0.0001). Within the PEG/ribivirin arm, end of treatment virologic response was 29% for HCV genotype 1 versus 80% for genotype non-1 (p = 0.0007) PEG/ribavirin was associated with a significantly higher sustained virologic response (HCV <60 IU/mL 24 weeks after end of therapy) than IFN/ribivirin (27 vs 12%, p < 0.03). Within the PEG/ribivirin arm, sustained virologic response was only 14% for genotype 1, compared with 73% for genotype non-1 (p = 0.0007). Independent predictors of sustained virologic response included receipt of PEG/ribivirin, HCV genotype non-1, no prior injection drug use, and a detectable HIV-1 RNA at entry. Histologic response was observed in 36% of virologic nonresponders and in 52% of virologic response who underwent liver biopsy. Both regimens were well tolerated. No loss of HIV disease control was observed. Failure to achieve >2-log HCV RNA reduction at week 12 uniformly predicted failure to accomplish sustained virologic response (100% negative predictive value). Similar frequencies of flu-like symptoms, depression, and laboratory abnormalities were observed in each arm, and premature discontinuation rates were low in each arm (12%).

CONCLUSIONS: PEG/ribivirin is superior to IFN/ribivirin in the treatment of chronic HCV in HIV-co-infected persons and is well tolerated without adverse effect on HIV disease. The marked genotype discrepancy in sustained virologic response indicates that strategies to improve outcome in genotype 1 HCV are needed. These regimens may provide clinical benefit even in the absence of virologic clearance.

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Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.