Treatment shows efficacy in patients with HIV, HCV

Two studies published in the July 29 issue of the New England Journal of Medicine have found high efficacy rates among patients coinfected with chronic hepatitis C virus (HCV) and HIV who were treated with pegylated interferon and ribavirin.

In the AIDS Pegasys Ribavirin International Coinfection Trial (APRICOT), researchers studied the efficacy and safety of combination therapy with peginterferon alfa-2a plus ribavirin in people coinfected with HCV and HIV in an international, randomized, placebo-controlled trial.

The researchers randomly assigned a total of 868 people who were infected with both HIV and HCV and who had not previously been treated with interferon or ribavirin to receive one of three regimens: peginterferon alfa-2a (180 µg per week) plus ribavirin (800 mg per day), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU three times a week) plus ribavirin. Patients were treated for 48 weeks and followed for an additional 24 weeks. The primary endpoint was a sustained virologic response.

The overall rate of sustained virologic response was significantly higher among the recipients of peginterferon alfa-2a plus ribavirin than among those assigned to interferon alfa-2a plus ribavirin (40% vs. 12%), or peginterferon alfa-2a plus placebo (40% vs. 20%). Among patients infected with HCV genotype 1, the rates of sustained virologic response were 29% with peginterferon alfa-2a plus ribavirin, 14% with peginterferon alfa-2a plus placebo, and 7% with interferon alfa-2a plus ribavirin. The corresponding rates among patients infected with HCV genotype 2 or 3 were 62%, 36%, and 20%.

Neutropenia and thrombocytopenia were more common among patients treated with regimens that contained peginterferon alfa-2a, and anemia was more common among patients treated with regimens containing ribavirin.

In the second, smaller study, researchers randomly assigned 66 subjects to receive 180 µg peginterferon alfa-2a weekly for 48 weeks, and 67 subjects to receive 6 million IU interferon alfa-2a three times weekly for 12 weeks followed by 3 million IU three times weekly for 36 weeks. Both groups received ribavirin according to a dose-escalation schedule. At week 24, subjects who did not have a virologic response underwent liver biopsy, and medications were continued in subjects with either a virologic response or histologic improvement.

Treatment with peginterferon and ribavirin was associated with a significantly higher rate of sustained virologic response than was treatment with interferon and ribavirin (27% vs. 12%). In the group given peginterferon and ribavirin, only 14% of subjects with HCV genotype 1 infection had a sustained virologic response (seven of 51), as compared with 73% of subjects with an HCV genotype other than genotype 1 (11 of 15). Histologic responses were observed in 35% of subjects with no virologic response who underwent liver biopsy.

The two studies show that a sustained virologic response can be achieved with pegylated interferon alfa and ribavirin therapy in a substantial proportion of coinfected patients, says Jean-Michel Pawlotsky, MD, PhD, a professor of medicine at University of Paris XII and the Chief of the Virology Unit in Department of Bacteriology and Virology at the Henri Mondor University Hospital INSERM Unit 99 in Creteil, France.

He wrote his comments in an accompanying editorial. "These results, together with the poor prognosis for HIV-positive patients with HCV infection, justify broad use of antiviral therapy in the treatment of coinfected patients."

However, future improvements in treatment outcomes in difficult-to-treat patients, including those who are coinfected with HCV and HIV, will require novel therapeutic approaches, Pawlotsky says.