Peginterferon Alfa-2a plus Ribavirin versus Interferon Alfa-2a plus Ribavirin for Chronic Hepatitis C in HIV-Coinfected Persons
Raymond T. Chung, M.D., Janet Andersen, Sc.D., Paul Volberding, M.D., Gregory K. Robbins, M.D., Tun Liu, M.S., Kenneth E. Sherman, M.D., Ph.D., Marion G. Peters, M.D., Margaret J. Koziel, M.D., Atul K. Bhan, M.D., Beverly Alston, M.D., Dodi Colquhoun, B.S., Tom Nevin, M.S., George Harb, M.D., Charles van der Horst, M.D., for the AIDS Clinical Trials Group A5071 Study Team
Background Chronic hepatitis C virus (HCV) infection is a causeof major complications in persons who are also infected withthe human immunodeficiency virus (HIV). However, the treatmentof HCV infection in such persons has been associated with ahigh rate of intolerance and a low rate of response. We conducteda multicenter, randomized trial comparing peginterferon plusribavirin with interferon plus ribavirin for the treatment ofchronic hepatitis C in persons coinfected with HIV.
Methods A total of 66 subjects were randomly assigned to receive180 µg of peginterferon alfa-2a weekly for 48 weeks, and67 subjects were assigned to receive 6 million IU of interferonalfa-2a three times weekly for 12 weeks followed by 3 millionIU three times weekly for 36 weeks. Both groups received ribavirinaccording to a dose-escalation schedule. At week 24, subjectswho did not have a virologic response (those who had an HCVRNA level greater than or equal to 60 IU per milliliter) underwentliver biopsy, and medications were continued in subjects witheither a virologic response or histologic improvement.
Results Treatment with peginterferon and ribavirin was associatedwith a significantly higher rate of sustained virologic response(an HCV RNA level of less than 60 IU per milliliter 24 weeksafter completion of therapy) than was treatment with interferonand ribavirin (27 percent vs. 12 percent, P=0.03). In the groupgiven peginterferon and ribavirin, only 14 percent of subjectswith HCV genotype 1 infection had a sustained virologic response(7 of 51), as compared with 73 percent of subjects with an HCVgenotype other than 1 (11 of 15, P<0.001). Histologic responseswere observed in 35 percent of subjects with no virologic responsewho underwent liver biopsy.
Conclusions In persons infected with HIV, the combination ofpeginterferon and ribavirin is superior to the combination ofinterferon and ribavirin in the treatment of chronic hepatitisC. These regimens may provide clinical benefit even in the absenceof virologic clearance. The marked discrepancy in the ratesof sustained virologic response between HCV genotypes indicatesthat strategies are needed to improve the outcome in personsinfected with HCV genotype 1.
Source Information
From Massachusetts General Hospital, Boston (R.T.C., G.K.R., A.K.B.); Harvard School of Public Health, Boston (J.A., T.L.); the University of California, San Francisco, San Francisco (P.V., M.G.P.); the University of Cincinnati, Cincinnati (K.E.S.); Beth Israel Deaconess Medical Center, Boston (M.J.K.); the National Institute of Allergy and Infectious Diseases, Bethesda, Md. (B.A.); Frontier Science Technology and Research Foundation, Amherst, N.Y. (D.C.); Social and Scientific Systems, Rockville, Md. (T.N.); Roche Laboratories, Nutley, N.J. (G.H.); and the University of North Carolina, Chapel Hill (C.H.).
Address reprint requests to Dr. Chung at GRJ 825, GI Unit, Massachusetts General Hospital, Boston, MA 02114, or at rtchung{at}partners.org.
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