Peginterferon Alpha-2b Plus Ribavirin vs Interferon Alpha-2b Plus Ribavirin
Peginterferon Alpha-2b Plus Ribavirin vs Interferon Alpha-2b Plus Ribavirin
Treatment of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients is associated with low response rates and high incidence of side effects. One hundred twenty-one hepatitis C virus (HCV)-HIV-coinfected patients were randomized to receive interferon alpha-2b (3 MU thrice weekly; n = 61) or peginterferon alpha-2b (1.5 μg/kg/week; n = 60), plus ribavirin (800 mg daily), for 24 (genotype 2 or 3) or 48 weeks (genotype 1 or 4). We assessed early virological response at 4, 8 and 12 weeks to predict sustained virological response (SVR). Safety assessment included frequent blood lactate measurement and relative quantitation of mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells. In intention-to-treat analysis, the SVR rate was higher in the peginterferon group (55%vs 26%; P = 0.002). The difference for HCV genotypes 1 and 4 was 45%vs 14% (P = 0.009) and 50%vs 27% (P = 0.387), respectively, and for genotype 2 or 3, 71%vs 43% (P = 0.12) Viral response at 4, 8 and 12 weeks of treatment was highly predictive of SVR. Among genotype 3 patients, 17 of 20 (85%) whose HCV RNA was already undetectable at 4 weeks had an SVR after 24 weeks of treatment. Hyperlactataemia occurred in 22 patients and was clinically significant in six, two of whom died. mtDNA decreased significantly 4-12 weeks after the start of treatment in patients developing clinically significant hyperlactataemia. Peginterferon alpha-2b plus ribavirin was more effective than interferon alpha-2b plus ribavirin in HIV-coinfected patients. Frequent monitoring of virological response may be very helpful to optimize treatment compliance, to tailor treatment duration and to minimize side effects.
Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is highly prevalent in patients who acquired HIV by the parenteral route.
The prolonged survival associated with the use of highly active antiretroviral therapy (HAART) and the increased incidence of drug-related hepatotoxicity and a more rapid evolution towards end-stage liver disease has made treatment of chronic hepatitis C in these patients a priority. Accordingly, it has been recommended that HIV-coinfected patients be considered candidates for treatment. Recently, data from multicentre trials in coinfected patients have shown a higher treatment efficacy with peginterferon and ribavirin over the standard interferon-ribavirin combination, although with response rates lower than those reported in HIV negative patients. Furthermore, severe side effects associated with mitochondrial toxicity, attributed to the effect of ribavirin in combination with certain nucleoside analogues, have been reported.
Here we report the results of a randomized trial comparing the safety and efficacy of peginterferon α-2b with those of interferon α-2b both in combination with ribavirin for the treatment of chronic hepatitis C in HIV-infected patients.
Summary and Introduction
Summary
Treatment of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients is associated with low response rates and high incidence of side effects. One hundred twenty-one hepatitis C virus (HCV)-HIV-coinfected patients were randomized to receive interferon alpha-2b (3 MU thrice weekly; n = 61) or peginterferon alpha-2b (1.5 μg/kg/week; n = 60), plus ribavirin (800 mg daily), for 24 (genotype 2 or 3) or 48 weeks (genotype 1 or 4). We assessed early virological response at 4, 8 and 12 weeks to predict sustained virological response (SVR). Safety assessment included frequent blood lactate measurement and relative quantitation of mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells. In intention-to-treat analysis, the SVR rate was higher in the peginterferon group (55%vs 26%; P = 0.002). The difference for HCV genotypes 1 and 4 was 45%vs 14% (P = 0.009) and 50%vs 27% (P = 0.387), respectively, and for genotype 2 or 3, 71%vs 43% (P = 0.12) Viral response at 4, 8 and 12 weeks of treatment was highly predictive of SVR. Among genotype 3 patients, 17 of 20 (85%) whose HCV RNA was already undetectable at 4 weeks had an SVR after 24 weeks of treatment. Hyperlactataemia occurred in 22 patients and was clinically significant in six, two of whom died. mtDNA decreased significantly 4-12 weeks after the start of treatment in patients developing clinically significant hyperlactataemia. Peginterferon alpha-2b plus ribavirin was more effective than interferon alpha-2b plus ribavirin in HIV-coinfected patients. Frequent monitoring of virological response may be very helpful to optimize treatment compliance, to tailor treatment duration and to minimize side effects.
Introduction
Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is highly prevalent in patients who acquired HIV by the parenteral route.
The prolonged survival associated with the use of highly active antiretroviral therapy (HAART) and the increased incidence of drug-related hepatotoxicity and a more rapid evolution towards end-stage liver disease has made treatment of chronic hepatitis C in these patients a priority. Accordingly, it has been recommended that HIV-coinfected patients be considered candidates for treatment. Recently, data from multicentre trials in coinfected patients have shown a higher treatment efficacy with peginterferon and ribavirin over the standard interferon-ribavirin combination, although with response rates lower than those reported in HIV negative patients. Furthermore, severe side effects associated with mitochondrial toxicity, attributed to the effect of ribavirin in combination with certain nucleoside analogues, have been reported.
Here we report the results of a randomized trial comparing the safety and efficacy of peginterferon α-2b with those of interferon α-2b both in combination with ribavirin for the treatment of chronic hepatitis C in HIV-infected patients.
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