C. Bradley Hare, UC San Francisco

Hepatitis C virus (HCV) infection is one of the most important causes of morbidity and mortality among people living with HIV/AIDS. Over 200,000 people in the Unites States, including 37,000 in California, are co-infected with HIV and HCV. At the San Francisco General Hospital HIV/AIDS Clinic, 37% of all HIV patients are co-infected with HCV, and the numbers are higher for women (59% co-infection) and African Americans (48% co-infection).

In the past, people with HCV/HIV co-infection often died from AIDS before HCV could cause serious problems. However, with improvements in HIV/AIDS care and treatment, more co-infected people are living longer and thus developing complications from HCV, including cirrhosis, hepatocellular carcinoma and death. HCV infection can also increase the hepatotoxicity of antiretroviral medications, limiting HIV treatment options. Treatment of chronic HCV infection has improved with the use of combination pegylated interferon (PEG-IFN) and ribavirin (RBV), but treatment success rates are significantly lower in the setting of HIV co-infection. Additionally, the significant toxicity of HCV therapy may cause morbidity or treatment discontinuation.

Recent research suggests that treatment of acute HCV infection with PEG-IFN monotherapy in individuals without HIV co-infection can result in high rates of sustained virologic response (SVR: defined as undetectable HCV RNA 24 weeks after the completion of therapy). It is not known whether similarly high SVR can be achieved in the setting of HIV co-infection. It has also been shown that and individual's early HCV viral response to therapy is associated with SVR. This study will examine whether it is possible to monitor each subject's early viral response kinetics to therapy and to tailor treatment based on that response in a "kinetically guided" approach, thereby optimizing SVR rates while simultaneously minimizing exposure to potentially toxic medications that might be unnecessary.

In this pilot study, 20 HIV-infected subjects with acute HCV infection will be treated with HCV therapy for 24 weeks. Because HIV co-infection is expected to impair HCV treatment response, treatment will be initiated with the potent combination of PEG-IFN and RBV. PEG-IFN will be continued for the full 24 weeks in all subjects, whereas RBV will be used for 12 or 24 weeks, based on each subject's individual HCV RNA response to the first 12 weeks of therapy. RBV will be discontinued at week 12 in subjects with undetectable HCV RNA at both weeks 8 and 12 of combination therapy, minimizing potentially unnecessary exposure to RBV among subjects with good treatment response. Alternatively, 24 weeks of RBV will be used in subjects with detectable HCV RNA at either week 8 or 12 of combination therapy, who thus demonstrate the need for continued combination therapy in order to maximize the likelihood of SVR. The primary endpoint for this study is the proportion of subjects with SVR. Treatment safety and tolerability will also be measured to determine the overall risks and benefits of this treatment approach.

Results from this study will both inform the management of acute HCV infection and provide preliminary data for subsequent comparative efficacy trials. Specifically, this pilot study will assess the feasibility of conducting such a study in HIV-infected patients with acute HCV infection and will inform the design of larger, randomized, controlled efficacy studies of acute HCV therapy.