Rx for HCV-Coinfection: Pegylated Interferon + Ribavirin
Rx for HCV-Coinfection: Pegylated Interferon + Ribavirin
Two studies confirm that combination therapy for HCV with pegylated interferon alfa-2a + ribavirin is the regimen of choice for HIV-coinfected patients.
Morbidity and mortality due to liver disease is an increasing concern in patients coinfected with hepatitis C virus (HCV) and HIV. In patients infected with HCV alone, combination therapy with pegylated interferon and ribavirin is the treatment of choice, providing the best chance of a sustained virologic response. Two research groups recently investigated whether this is also the optimal regimen for HIV-coinfected patients.
In the manufacturer-sponsored AIDS Pegasys Ribavirin International Coinfection Trial (APRICOT), researchers randomized HIV/HCV-coinfected patients to one of three treatment arms: (1) interferon alfa-2a three times weekly plus oral ribavirin twice daily, (2) pegylated interferon alfa-2a once weekly plus placebo twice daily, or (3) pegylated interferon alfa-2a plus ribavirin twice daily. The investigators and subjects were blinded as to whether oral therapy was ribavirin or placebo. Treatment was provided for 48 weeks, with follow-up lasting an additional 24 weeks. Patients were required to have compensated liver disease and a stable antiretroviral regimen. The primary endpoint was a sustained virologic response, defined as undetectable HCV RNA (<50 IU/mL) at the end of follow-up. Early virologic response was defined as an undetectable HCV RNA or a decrease of >2 log in serum HCV RNA at treatment week 12 or 24.
The 860 patients who were enrolled and treated were predominantly white (79%) and male (81%), and had well-controlled HIV infection (mean CD4 count >500 cells/mm; 60% with HIV viral load <50 copies/mL). At the end of follow-up, sustained virologic response was seen in 40% of patients randomized to pegylated interferon + ribavirin, 20% of patients randomized to pegylated interferon and placebo, and 12% of the patients randomized to standard interferon + ribavirin. Pegylated interferon + ribavirin performed best of the three regimens regardless of HCV genotype, although rates of sustained virologic response were significantly lower across-the-board in patients with genotype 1 compared with those who had genotype 2 or 3. In a multivariate analysis, a genotype other than type 1 and pretreatment HCV RNA of no more than 800,000 IU/mL both predicted sustained virologic response (odds ratios, 3.37 and 3.56, respectively). An early virologic response at treatment week 12 was predictive of sustained response at the end of follow-up in all treatment groups; 30%, 37%, and 56% of patients with an early response achieved a sustained response at week 24 of post-therapy follow-up in the standard interferon, pegylated interferon, and pegylated interferon and ribavirin groups, respectively. Of the patients who did not achieve an early virologic response, only two went on to attain a sustained response. Significant cytopenia requiring reduction in treatment dose or administration of a hematopoietic growth factor was more frequent in both groups treated with pegylated interferon, but withdrawal from treatment due to adverse events did not differ among treatment groups.
Similar results were seen in a smaller NIH-sponsored study. Researchers randomized 133 HIV/HCV-coinfected patients to receive either pegylated interferon alfa-2a weekly for 48 weeks or standard interferon alfa-2a at 6 million IU three times weekly for 12 weeks followed by 3 million IU three times weekly for 36 weeks. Both regimens were combined with ribavirin. Twenty-four weeks after cessation of therapy, 27% of patients receiving pegylated interferon had a sustained virologic response (HCV viral load <60 IU/mL) compared with 12% of those receiving standard interferon. Again, HCV genotype had a profound influence: Among patients with genotype 1, sustained response occurred in only 14% and 6% of patients receiving pegylated and standard interferon, respectively. Among those with genotype 2 or 3, 73% and 33% of patients receiving pegylated and standard interferon, respectively, had a sustained response.
These reports confirm results from earlier studies in HCV-monoinfected patients, suggesting that treatment with pegylated interferon alfa-2a + ribavirin provides a better chance at a sustained response than does pegylated interferon alone or standard interferon alfa-2a + ribavirin. The lower response rate in the NIH study has been attributed to the lower initial dose of ribavirin. An important finding of both studies was that virologic response at 12 weeks was predictive of sustained virologic response. This information can be helpful in counseling patients who are considering the risks and benefits of HCV treatment. If patients can make it to 12 weeks of therapy, their progress can be reassessed and they can make reasonably informed decisions about whether to continue therapy for a full course. Questions remain about how treatment response can improved in coinfected patients and whether interferon provides histologic benefit even in the absence of virologic response.
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Two studies confirm that combination therapy for HCV with pegylated interferon alfa-2a + ribavirin is the regimen of choice for HIV-coinfected patients.
Morbidity and mortality due to liver disease is an increasing concern in patients coinfected with hepatitis C virus (HCV) and HIV. In patients infected with HCV alone, combination therapy with pegylated interferon and ribavirin is the treatment of choice, providing the best chance of a sustained virologic response. Two research groups recently investigated whether this is also the optimal regimen for HIV-coinfected patients.
In the manufacturer-sponsored AIDS Pegasys Ribavirin International Coinfection Trial (APRICOT), researchers randomized HIV/HCV-coinfected patients to one of three treatment arms: (1) interferon alfa-2a three times weekly plus oral ribavirin twice daily, (2) pegylated interferon alfa-2a once weekly plus placebo twice daily, or (3) pegylated interferon alfa-2a plus ribavirin twice daily. The investigators and subjects were blinded as to whether oral therapy was ribavirin or placebo. Treatment was provided for 48 weeks, with follow-up lasting an additional 24 weeks. Patients were required to have compensated liver disease and a stable antiretroviral regimen. The primary endpoint was a sustained virologic response, defined as undetectable HCV RNA (<50 IU/mL) at the end of follow-up. Early virologic response was defined as an undetectable HCV RNA or a decrease of >2 log in serum HCV RNA at treatment week 12 or 24.
The 860 patients who were enrolled and treated were predominantly white (79%) and male (81%), and had well-controlled HIV infection (mean CD4 count >500 cells/mm; 60% with HIV viral load <50 copies/mL). At the end of follow-up, sustained virologic response was seen in 40% of patients randomized to pegylated interferon + ribavirin, 20% of patients randomized to pegylated interferon and placebo, and 12% of the patients randomized to standard interferon + ribavirin. Pegylated interferon + ribavirin performed best of the three regimens regardless of HCV genotype, although rates of sustained virologic response were significantly lower across-the-board in patients with genotype 1 compared with those who had genotype 2 or 3. In a multivariate analysis, a genotype other than type 1 and pretreatment HCV RNA of no more than 800,000 IU/mL both predicted sustained virologic response (odds ratios, 3.37 and 3.56, respectively). An early virologic response at treatment week 12 was predictive of sustained response at the end of follow-up in all treatment groups; 30%, 37%, and 56% of patients with an early response achieved a sustained response at week 24 of post-therapy follow-up in the standard interferon, pegylated interferon, and pegylated interferon and ribavirin groups, respectively. Of the patients who did not achieve an early virologic response, only two went on to attain a sustained response. Significant cytopenia requiring reduction in treatment dose or administration of a hematopoietic growth factor was more frequent in both groups treated with pegylated interferon, but withdrawal from treatment due to adverse events did not differ among treatment groups.
Similar results were seen in a smaller NIH-sponsored study. Researchers randomized 133 HIV/HCV-coinfected patients to receive either pegylated interferon alfa-2a weekly for 48 weeks or standard interferon alfa-2a at 6 million IU three times weekly for 12 weeks followed by 3 million IU three times weekly for 36 weeks. Both regimens were combined with ribavirin. Twenty-four weeks after cessation of therapy, 27% of patients receiving pegylated interferon had a sustained virologic response (HCV viral load <60 IU/mL) compared with 12% of those receiving standard interferon. Again, HCV genotype had a profound influence: Among patients with genotype 1, sustained response occurred in only 14% and 6% of patients receiving pegylated and standard interferon, respectively. Among those with genotype 2 or 3, 73% and 33% of patients receiving pegylated and standard interferon, respectively, had a sustained response.
These reports confirm results from earlier studies in HCV-monoinfected patients, suggesting that treatment with pegylated interferon alfa-2a + ribavirin provides a better chance at a sustained response than does pegylated interferon alone or standard interferon alfa-2a + ribavirin. The lower response rate in the NIH study has been attributed to the lower initial dose of ribavirin. An important finding of both studies was that virologic response at 12 weeks was predictive of sustained virologic response. This information can be helpful in counseling patients who are considering the risks and benefits of HCV treatment. If patients can make it to 12 weeks of therapy, their progress can be reassessed and they can make reasonably informed decisions about whether to continue therapy for a full course. Questions remain about how treatment response can improved in coinfected patients and whether interferon provides histologic benefit even in the absence of virologic response.
Click here for AIDS Clinical Care subscription information.