BRUSSELS, Belgium -- Patients co-infected with chronic hepatitis C virus (HCV) and HIV treated with PegIntron(R) (peginterferon alfa-2b) and Rebetol(R) (ribavirin) combination therapy achieved significantly higher rates of sustained viral response (SVR) compared to those treated with the combination of Intron(R) A (interferon alfa-2b) plus Rebetol, 44 percent vs. 21 percent (p=0.017), respectively, according to results of a new study published in the September 3, 2004, issue of AIDS(1), the official peer-reviewed journal of the International AIDS Society (IAS). SVR, defined as the sustained undetectability of HCV six months following the end of treatment, was the primary endpoint of the study.
Importantly, for patients with the most difficult-to-treat HCV genotypes one or four, SVR rates were 38 percent in the PegIntron plus Rebetol group vs. seven percent in the Intron A plus Rebetol group (p=0.007), a statistically significant improvement. SVR rates in patients with HCV genotypes two or three were 53 percent vs. 47 percent (p=0.730), in these groups, respectively. Genotype one virus is the most common worldwide and the most difficult to treat successfully. Genotype four virus is the predominate type of HCV in the Middle East and is also considered to be difficult to treat. Infection rates with Genotypes two and three vary by geography and account for approximately 30 percent to 50 percent of HCV infections among European patients.
The majority of side effects in the study were mild or moderate, with treatment discontinuation due to adverse effects being similar in both the PegIntron plus Rebetol and Intron A plus Rebetol arms, 17 percent and 12 percent, respectively (p=0.565).
"In our study, peginterferon alfa-2b plus ribavirin achieved significantly higher sustained response rates than standard interferon combination therapy in the treatment of chronic hepatitis C in HIV co-infected patients, with twice as many patients overall achieving a sustained virologic response. Even more promising for patients, our study showed significant improvement over standard interferon combination therapy in the most difficult to treat HCV genotypes one and four," said Josep Mallolas, MD, PhD, Infectious Diseases Unit, Hospital Clinic Universitari de Barcelona, Spain. "For patients already taking numerous medications daily to manage their HIV infection, the activity and tolerability of this combination therapy, and the once-weekly dosing of peginterferon alfa-2b, may be an important step forward in treatment."
Study and Results
In this prospective, single-center, randomized open-label trial, 95 previously untreated HCV patients co-infected with HIV were randomly assigned to treatment with Intron A (three MIU three times weekly) or PegIntron (100-150 mcg once weekly, adjusted to body weight) plus Rebetol (800-1,200 mg daily, adjusted to body weight). Of these patients, 68 percent were males; 82 percent had a history of intravenous drug use; 63 percent had genotype one or four virus; 36 percent had genotype two or three virus; 62 percent had a fibrosis index greater than or equal to grade two and one-third had bridging fibrosis or cirrhosis. Duration of treatment was 48 weeks except for patients with HCV genotype two or three and low viral load (baseline HCV-RNA <800,000 IU/ml), who were treated for 24 weeks. The average time of known HCV infection was 17 years and the mean duration of previous treatment for HIV infection was 63 months. Eighty-four patients (88 percent) were taking HIV medications during the study period.
The side-effect profiles of patients taking both the PegIntron and Intron A combination therapies were similar, with no unexpected or unique adverse events reported. Flu-like symptoms were the most frequently reported adverse event, occurring in 82 percent of patients at the beginning of treatment and generally improving after a few weeks. Anemia was the most frequent hematological adverse event, occurring in 27 percent of patients. Side effects led to treatment discontinuation in nine patients (17 percent) in the PegIntron plus Rebetol group and in five patients (12 percent) in the Intron A plus Rebetol group (p=0.565). No growth factors (neither granulocyte-colony stimulating factor nor erythropoietin) were used in this study.
In the study, 43 percent of patients developed symptoms of depression (sadness, tiredness, apathy) during the therapy (37 percent in the PegIntron plus Rebetol group vs. 51 percent in the Intron A plus Rebetol group). Most of these were not severe and improved with antidepressant therapy, without reduction or cessation of HCV therapy. Mitochondrial toxicity, a side effect well described in the literature in co-infected patients on anti-retroviral therapy (ART) who begin HCV therapy, occurred in four percent of patients. Although most cases were asymptomatic, concomitant use of ribavirin plus ART containing nucleoside analogues like didanosine or stavudine, should be used with caution or are not recommended.
"This study, as well as the previously reported results of the community-based PegIntron RIBAVIC study in co-infected patients, are encouraging, particularly in patients with more difficult to treat HCV genotype one, and further underscore the value of individualized, weight-based PegIntron and Rebetol combination therapy," said Robert J. Spiegel, MD, chief medical officer and senior vice president of medical affairs, Schering-Plough Research Institute.
The study was supported in part by research grants from Schering-Plough.