Results from APRICOT Trial Report the Highest Response Rates Ever Achieved for the Treatment of Hepatitis C in HIV-HCV Co-infected Patients

New findings appearing in the July 29, 2004 issue of The New England Journal of Medicine (NEJM) reveal the highest efficacy rates ever reported among patients living with HIV-HCV coinfection who were treated with peginterferon and ribavirin. In the United States alone, approximately 300,0000 Americans are coinfected with hepatitis C and HIV.

The study investigators report 40 percent overall efficacy (sustained virological response rate) among coinfected patients. When analyzed by genotype, the investigators report 62 percent efficacy in patients with genotypes 2 and 3, and 29 percent in those with genotype 1, which is the most difficult form of the disease to treat successfully and also the most commonly occurring genotype in the US and Europe.

Several international medical centers released announcements of their interpretations of the significance of the published results of this international trial. Following are excerpts from the announcement by the Mount Sinai School of Medicine.

Mount Sinai School of Medicine Announcement

The multinational APRICOT trial (AIDS PEGASYS Ribavirin International CO-infection Trial) found that the drug combination of Pegasys (peginterferon alfa-2a) and Copegus (ribavirin) was much more effective than the previous generation of hepatitis C therapy, standard interferon and ribavirin. Efficacy was measured as the sustained virological response (SVR) rate, which is defined by the absence of detectable HCV RNA in the serum for at least six months after treatment.

HCV and HIV are the two most prevalent blood-borne infections in the United States. Of the nearly one million people estimated to have HIV in the U.S., approximately 300,000 are believed to be co-infected with HCV.

It can take 10 to 20 years following infection with hepatitis for a person to progress to end stage liver disease. However, in patients with HIV, the disease progresses far more quickly. With advances in HIV therapy prolonging the life expectancy of HIV patients, hepatitis C is now a major threat to people with HIV.

“The results of this study are groundbreaking news for the hundreds of thousands of Americans who are living with both hepatitis C and HIV," said Dr. Douglas Dieterich, Professor of Medicine, Mount Sinai School of Medicine, New York City and co-lead investigator of the APRICOT study. "These are patients who have fought long and hard to control their HIV -- for them to ultimately be defeated by a manageable disease like hepatitis C is unacceptable."

The APRICOT study reports four times more genotype 1 patients cleared the hepatitis C virus with Pegasys in combination with Copegus than with those treated with standard interferon/ribavirin combination therapy (29% vs. 7% respectively).

Additionally, Pegasys monotherapy showed superior efficacy to treatment with standard interferon and ribavirin (20 percent vs. 12 percent), which is important for patients who cannot tolerate ribavirin.

More About the APRICOT Trial

The randomized, partially blinded international trial enrolled a total of 868 HCV-HIV co-infected patients in 19 countries, and is currently the largest study conducted among this patient population. All patients were HCV positive, had compensated liver disease, a CD4+ count greater than 100 cells/mL, and stable HIV disease, with or without antiretroviral therapy.

Patients were randomized to 48 weeks of treatment with interferon three times a week plus 800 mg/day of ribavirin, 180 mcg of Pegasys once weekly plus placebo, or 180 mcg of Pegasys once weekly with 800 mg/day of Copegus.

Sustained virological response (SVR) was assessed at the end of 24 weeks of treatment-free follow up (week 72). Negative predictability ranged from 98 to 100 percent at 12 weeks. Negative predictability means that patients can determine by week 12 if they are unlikely to respond to therapy with Pegasys so that decisions about the continuance of treatment can be made in that time.

In addition, HIV viral levels were not negatively impacted by treatment with Pegasys and Copegus combination therapy, and no new safety concerns were reported with this study. The most commonly reported side effects were fatigue, fever and headache.

Final 72-WEEK RESULTS are shown in Table 1 below

Conclusions

Based on these study results, the authors conclude, “Based on an SVR of 40%, Pegasys + Copegus is the preferred treatment for HCV in co-infected patients. Further analysis of efficacy and safety data is ongoing to delineate the benefit/risk of the study treatment in specific subpopulations.”

Study Co-authors

Co-authors on the study include J. Torriani, University of California, San Diego, CA; J. Rockstroh, University of Bonn, Bonn, Germany; M. Rodriguez-Torres, Fundacion de Investigacion de Diego, Santurce, Puerto Rico; E. Lissen, Virgen del Rocío University Hospital, Seville, Spain; J. González, Hospital La Paz, Madrid, Spain; A. Lazzarin, San Raffaele Vita-Salute University, Milan, Italy; G. Carosi, University of Brescia, Italy; J. Sasadeusz, Royal Melbourne Hospital, Australia; C. Katlama, Groupe Hospitalier de la Pitie Salpetriere, Paris, France; J. Montaner, University of British Columbia, Vancouver, Canada; H. Sette, Instituto de Infectologia Emilio Ribas, Sao Paulo, Brazil; F. Duff, Roche, Nutley, NJ, USA , J. DePamphilis, Roche, Nutley, NJ, USA; U. M. Schrenk, Roche, Basel; Switzerland.

Roche, the developers of Pegasys, funded the study.

07/29/04

Reference

F J Torriani and others (for the APRICOT Study Group). Peginterferon Alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection in HIV-infected Patients. The New England Journal of Medicine 351(5): 438-450. July 29, 2004.

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