By Liz Highleyman

Standard therapy with pegylated interferon plus ribavirin has limited efficacy in "hard-to-treat" patients, including individuals with hepatitis C virus (HCV) genotype 1, HIV positive patients, and people of African descent.

Researchers have therefore investigated various strategies for intensifying and individualizing therapy, including higher drug doses, more frequent administration, and longer treatment duration.

In a study presented this week at the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008) in Washington, DC, researchers compared virological response in HIV-HCV genotype 1 coinfected patients randomly assigned to receive either standard therapy with once-weekly 180 mcg pegylated interferon alfa-2a (Pegasys) for 48 weeks (n = 10) or 180 mcg pegylated interferon twice-weekly for 4 weeks followed by once-weekly for 44 weeks (n = 9); all participants also received 1000-1200 mg daily ribavirin.

Liver function tests, HCV and HIV viral load, and immunologic parameters were assessed prior to and at frequent intervals during treatment.

Results

• The following parameters were all significantly lower in patients who received the double dose of pegylated interferon compared with the standard dose:

• HCV viral load on day 5 (P < 0.03);

• HCV RNA on day 7 (P < 0.05);

• Slope of HCV viral decline from day 0 to day 28 (P < 0.04);

• Pharmacodynamic parameters measuring threshold of antiviral regimen (P < 0.04);

• Time to ALT normalization (P < 0.03).

• Among African-American patients, the decline in HCV viral load was also significantly greater in those who received the double dose of pegylated interferon (P < 0.04).

• The study was not powered to show a difference in sustained virological response (SVR) between the standard dose and double dose groups (40% vs 45% respectively).

Based on these findings, the researchers concluded that, "Twice weekly [pegylated interferon] is associated with better early viral kinetics, particularly among African Americans, with similar safety profiles when compared with standard therapy."

"These improvements in early HCV kinetics may improve the SVR [rate] among HIV-HCV coinfected individuals," they added. "When confirmed in larger randomized clinical trials, this may provide a novel therapeutic approach to improve SVR among HIV-HCV coinfected African American subjects."

NIAID/NIH, Bethesda, MD; Bar Ilan Univ., Ramt Dan, Israel; CCMD, NIH, Bethesda, MD.

10/31/08

Reference
AA Murphy, I Rozenberg, MA Polis, and others. Twice-Weekly Peg IFN-alpha-2a with Ribavirin Improves Early Viral Kinetics over Standard Therapy among HIV/HCV Co-Infected African American Patients. 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract V-4220.