"Hepatitis C has become the new opportunistic infection among HIV-infected patients," says Raymond Chung, MD, director of the Center for Liver Disorders in the Gastrointestinal Unit at Massachusetts General Hospital (MGH), who led the study. "About 25 percent of those with HIV are coinfected with HCV, largely because these viruses share modes of transmission. The problem is immense and growing."
Chung notes that what had been the standard treatment for those infected with HCV only – interferon and ribavirin – was not effective for patients also infected with HIV. In those with both viruses, control of HCV levels in the blood was diminished and side effects were more pronounced, leading many patients to stop therapy. Recently, the FDA has approved a treatment for HCV-only infection using a chemically modified form of interferon, which keeps the drug active in the body for a longer period of time. The current study was designed to investigate whether this new approach could safely improve treatment success in those infected with both viruses.
Researchers at 21 centers around the U.S. enrolled patients infected with both HCV and HIV who had not previously received interferon treatment. The 133 enrolled patients were randomized to receive either the newer drug peginterferon and ribavirin or the previous standard treatment of interferon and ribavirin. Halfway through the 48-week study period, blood tests were taken to see whether HCV blood levels had dropped in response to therapy. Participants who did not show a viral response had liver biopsies to determine whether the treatment had reduced liver damage. Those who exhibited either viral clearance or improved liver biopsy findings continued with the experimental treatment, while those with no response discontinued therapy.
At the end of the study period, about 40 percent of those receiving peginterferon had cleared HCV from their bloodstream, compared with only 12 percent of the interferon group. Followup blood tests were taken 24 weeks after the study period, and again those in the peginterferon group fared significantly better, with 27 percent showing sustained clearance of HCV compared to 12 percent in the interferon group. The number of participants who discontinued treatment because of side effects was low, at a level similar to that seen in patients with HCV only, and no participants showed progression of HIV symptoms or adverse drug interactions with their anti-HIV drugs.
"This is really a foot in the door, a promise that we will be able to help many of these patients without adversely affecting control of their HIV disease," says Chung, an assistant professor of Medicine at Harvard Medical School. "Even among those who failed to clear HCV from their blood, over one third of those receiving treatment were found to have improved liver biopsies, which suggests that maintenance therapy with peginterferon at doses that do not clear virus could still help prevent the progression of liver disease."
The study, supported by grants from the National Institute of Allergy and Infectious Diseases, was conducted through the AIDS Clinical Trial Group. Chung's co-authors are Gregory Robbins, MD, and Atul Bhan, MD, of the MGH; Janet Andersen, ScD, and Tun Liu, Harvard School of Public Health; Paul Volberding, MD, and Marion Peters, MD, University of California at San Francisco; Kenneth Sherman, MD, PhD, University of Cincinnati; Margaret Koziel, Beth Israel Deaconess Medical Center; Beverly Alston, MD, National Institute of Allergy and Infectious Diseases; Dodi Colquhoun, Frontier Science Technology and Research Foundation; Tom Nevin, Social and Scientific Systems; George Harb, MD, Roche Laboratories; and Charles van der Horst, MD, University of North Carolina at Chapel Hill.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $400 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.
Journal
New England Journal of Medicine