|
Date of Report: 11/06/2002
Author: Laurence Peiperl, MD, Medical Director, AETC NRC
Source: National Resource Center
Description: Coverage of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
HIV and Hepatitis C Coinfection
ANRS HC02 - Ribavic: A Randomized Controlled Trial of Pegylated-Interferon alfa-2b plus Ribavirin vs Interferon alfa-2b plus Ribavirin for the Initial Treatment of Chronic Hepatitis C in HIV Co-Infected Patients
This randomized, open-label trial in 416 patients with both HIV and hepatitis C compares
standard interferon (IFN alpha-2b: 3 MIU 3 times per week, n = 210) to pegylated interferon (PEG-IFN alpha-2b: 1.5 mcg/kg once per week, n = 206), each combined with ribavirin 800 mg once per day. Duration of treatment was 48 weeks. Participants had positive HCV RNA and abnormal liver histology on biopsy within 18 months prior to study entry (39% had moderate to severe fibrosis) with CD4 count >200 cells/mm3 (mean CD4 count 515 cells/mm3) and stable HIV RNA (<200 copies/mL in 60% of participants; mean HIV viral load 3.48 log in others), and at entry were either taking stable antiretroviral therapy (80% of participants) or not taking antiretroviral therapy at all. HCV genotype 1 or 4 (less responsive to available treatments than genotypes 2 and 3) was present in 69% of subjects. Mean ALT level was 2.2 times upper limit of normal.
The primary efficacy endpoint of the study is absence of detectable hepatitis C RNA at week 72 of follow-up. Safety and tolerability are also evaluated. Preliminary results from an analysis of 319 participants at the 48 week time point were presented at ICAAC. In an intention-to-treat analysis, HCV viral load was undetectable in 24% of the standard interferon group and in 38% of the pegylated interferon group. (p = .01). While there was no difference in outcome detected at 48 weeks in subjects with the "easy-to-treat" HCV subtypes 2 and 3, patients with subtypes 1 or 4 had a greater chance of responding to treatment with pegylated interferon + ribavirin (28%) than to standard interferon + ribavirin (10%) (p < .001). Significant adverse events occurred in approximately 21-25% of participants, and were similar between groups.
Based on these preliminary results, pegylated interferon appears superior to standard interferon in treating patients coinfected with HIV and HCV genotypes 1 or 4, although response rates appear lower than in patients with HCV alone. These findings are consistent with preliminary results of protocol ACTG 5071, presented earlier this year (Chung, et al).
In a related presentation by Hor, et al, on the Ribavic study, mitochondrial toxicity (hyperlactatemia or pancreatitis) was reported in 16% of subjects receiving didanosine (odds ratio 23; 95% confidence interval 5-105), suggesting that didanosine should be avoided in patients receiving interferon/ribavirin treatment for hepatitis C.
Perronne C, Carrat F, Banisadr F, Morand P, Lunel F, Rosenthal E, and Pol S. ANRS HC02 - RIBAVIC: A Randomized Controlled Trial of Pegylated-Interferon alfa-2b plus Ribavirin vs Interferon alfa-2b plus Ribavirin for the Initial Treatment of Chronic Hepatitis C in HIV Co-Infected Patients. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, September 27 - 30, 2002, San Diego, California, Abstract H-1083.
Chung et al. A randomized, controlled trial of pegylated interferon-a-2a with ribavirin vs interferon-a-2a with ribavirin for the treatment of chronic HCV in HIV co-infection. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, Washinton. February 24-28, 2002, Abstract LB-15.
Hor T, Deshayes J, Banisadr F, Pol S, Rosenthal E, Carrat F, and Perronne C. Concomitant ddI/d4T and IFN (Standard or Pegylated)/Ribavirin Treatments May Induce a High Risk of Mitochondrial Toxicity in HIV/HCV infected Patients (ANRS HC02- ribavic study). 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, September 27 - 30, 2002, San Diego, California, Abstract H-1735.
|
