July 28, 2004

International Study Shows Safe, Effective Therapy
For Previously Untreated Patients With HIV & Hepatitis C

By Sue Pondrom

An international study with nearly 900 patients co-infected with Human Immunodeficiency Virus (HIV) and hepatitis C virus (HCV) has shown that HCV can be treated effectively and safely, without compromising the patient’s HIV therapy.

Currently, HCV and resulting end-stage liver disease is the major cause of hospitalization and death in the more than one-third of HIV patients who are co-infected with HCV. While potent anti-viral therapies have prolonged the lives of HIV patients, HCV has emerged as the leading cause of liver disease and death in co-infected patients. And yet, most co-infected individuals go undiagnosed and untreated for their hepatitis.

Published in the July 29, 2004 edition of the New England Journal of Medicine, the study found that a combination therapy with peginterferon alfa-2a weekly injections plus oral ribavirin at a fixed 800 mg daily, achieved an overall 40 percent sustained virological response to HCV – the highest ever reported in a trial of co-infected patients. At the same time, investigators determined that the HCV treatment did not interfere with the effectiveness of HIV drugs.

“This is a major breakthrough that shifts the paradigm of treating hepatitis C in HIV co-infected patients,” said the study’s co-lead investigator, Francesca Torriani, M.D., associate professor of medicine, Antiviral Research Center, University of California, San Diego (UCSD) School of Medicine.

“To date, there has been considerable anxiety in treating co-infected patients due to concern that the HCV drug would be less effective than in people with HCV only, and that they would interfere with HIV control,” Torriani said. “In addition, physicians have worried about unacceptable toxicities such as lowered white blood count and anemia. As a result, nearly all co-infected HIV/HCV patients have not been treated.”

Taking place over a three-year period at 95 centers in 19 countries, the study was named AIDS Pegasys Ribavirin International Co-Infection Trial, or APRICOT. The 868 patients in the trial were randomized to receive either once-weekly peginterferon alfa-2a injections plus oral ribavirin (the current standard-of-care for patients with HCV monoinfection), a conventional interferon therapy with interferon alfa-2a plus ribavirin, or peginterferon alfa-2a therapy with a ribavirin placebo (inactive ribavirin). Patients received medications for 48 weeks and were then followed for another 24 weeks off treatment, until week 72, when sustained virologic response, the primary endpoint, was assessed. Sustained virologic response was defined as absence of HCV virus in the blood.

The sustained virologic responses were broken down by HCV genotype. Genotype 1 is the most common (about 70 percent of cases in the United States) as well as the most difficult to treat. Another 30 percent of HCV patients are infected with either genotypes 2 or 3. In the APRICOT study, genotype 1 patients on peginterferon alfa-2a plus ribavirin achieved a four-fold increase in sustained virological response compared to conventional interferon plus ribavirin (29 percent vs. 7 percent) and a rate double that of the peginterferon alfa-2a plus placebo (29 percent vs. 14 percent). Genotype 2 and 3 patients had a 62 percent sustained virological response with peginterferon alfa-2a plus ribavirin, as compared to 20 percent for the conventional interferon plus ribavirin and 36 percent for the peginterferon alfa-2a plus placebo.

A sub study within APRICOT, which looked at potential interactions between some HIV drugs (nucleoside HIV reverse transcriptase inhibitors) and ribavirin, found no interactions, Torriani said. In addition, investigators were surprised to note that HIV viral load slightly decreased in patients treated with peginterferon alfa-2a arms during the trial.

Torriani’s co-lead investigator in the study was Douglas T. Dieterich, M.D., vice chair and chief medical officer, Mount Sinai School of Medicine, New York. Additional authors were Maribel Rodriguez-Torres, M.D., the Fundacion de Investigacion de Diego, Santurce, Puerto Rico; Jurgen K. Rockstroh, M.D., the University of Bonn, Germany; Eduardo Lissen, M.D., Virgen del Rocio University Hospital, Seville, Spain; Juan Gonzalez-Garcia, M.D., Unidad Virus de la Immunodeficiencia Humana, Hospital Universitario La Plaz, Madrid, Spain; Adriano Lazzarin, M.D., Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Vita-Salute University, Milan, Italy; Giampiero Carosi, M.D., Department of Infectious and Tropical Diseases, University of Brescia, Italy; Jospeh Sasadeusz, M.D., Alfred Hospital, Melbourne, Australia; Christine Katlama, M.D., Groupe Hospitalier de la Pitie-Salpetriere, Paris, France; Julio Montaner, M.D., University of British Columbia, Vancouver, Canada; Hoel Sette, Jr., M.D., Instituto de Infectologia Emilio Ribas, Sao Paulo, Brazil; Sharon Passe, M.S., Jean De Pamphilis, Ph.D. and Frank Duff, M.D., Roche, Nutley, New Jersey; and Uschi Marion Schrenk, M.D., Roche, Basel, Switzerland. The study was funded by Roche, a pharmaceutical company based in Switzerland.

Media Contacts: Sue Pondrom (619) 543-6163