07/09/13FROM THE LANCET INFECTIOUS DISEASES
Among adults infected with both HIV and hepatitis C virus, the addition of boceprevir to a combination of peginterferon and ribavirin significantly increased the rate of sustained virological response compared with those who received placebo, results from a 44-week, multicenter phase II study demonstrated.
"Rates of SVR at follow-up week 24 were increased with boceprevir in all subgroups of patients, irrespective of demographic or baseline characteristics," researchers led by Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, reported in the July issue of the Lancet Infectious Diseases. Although SVR after treatment with peginterferon and ribavirin has been associated with improved survival, "this regimen has been relatively ineffective (SVR, 25%-30%) in patients with HIV and HCV genotype 1 infection," they wrote.
"Addition of an HCV protease inhibitor (boceprevir or telaprevir) to peginterferon-ribavirin has emerged as the standard of care for the treatment of HCV genotype 1 infection alone. Use of HCV protease inhibitors in patients infected with HIV and HCV has been restricted by the dearth of available safety and efficacy data."
For the study, which was conducted between Jan. 15 and Dec. 29, 2010, at 30 academic and nonacademic study sites, 99 adults with untreated HCV type 1 genotype infection and controlled HIV were randomized in 1:2 fashion to receive peginterferon 1.5 mcg/kg per week with weight-based ribavirin (600-1,400 mg/day) for 4 weeks, followed by peginterferon-ribavirin plus either placebo (control group) or 800 mg of boceprevir three times daily (boceprevir group) for 44 weeks (Lancet Infect. Dis. 2013;13:597-605).
The primary endpoint of interest was sustained virological response (defined as undetectable plasma HCV RNA) at follow-up week 24 after the end of treatment.
Of the 99 patients, 98 received at least one treatment dose. Of these, 64 were in the boceprevir group and 34 were in the control group. The researchers reported that at follow-up week 24, 63% of patients in the boceprevir group achieved SVR, compared with 29% of controls, a difference of 33.1% that reached significance (P = .0008). Compared with controls, a higher proportion of the boceprevir group experienced adverse events, including anemia (41% vs. 26%, respectively), pyrexia (36% vs. 21%), decreased appetite (34% vs. 18%), dysgeusia (28% vs. 15%), vomiting (28% vs. 15%), and neutropenia (19% vs. 6%). In addition, 4 patients in the control group and 3 in the boceprevir group had HIV viral breakthrough, defined as two consecutive HIV RNA values of at least 50 copies/mL.
"Boceprevir did not seem to add significant risk when used in combination with peginterferon-ribavirin therapy, and no new adverse events were reported," the researchers wrote. "HIV control was well maintained in patients taking boceprevir and HIV protease inhibitors. Drug interactions between boceprevir and HIV protease inhibitors did not have a clinically significant effect on HCV response or HIV control in this study. In view of the hepatic and extrahepatic benefits associated with SVR at follow-up week 24 in patients infected with HIV and HCV, boceprevir in combination with peginterferon-ribavirin might be an important therapeutic option for patients with such coinfection."
Merck markets boceprevir under the brand name Victrelis. Merck sponsored and funded the study. Dr. Sulkowski and numerous other coauthors disclosed having received consulting fees and research grants from the company.