The Impact of HAART on Response to Hepatitis C Treatment in Patients Taking Peginterferon Alpha-2b and Ribavirin

Coinfection with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) has risen dramatically since the explosion of the HIV pandemic twenty years ago, with one third of all HIV positive persons also infected with HCV. Numerous studies have suggested that HIV exacerbates several steps in the natural history of hepatitis C, and as survival among HIV-infected patients increases, hepatitis C-related morbidity and mortality is expected to follow a similar trend in coinfected patients. Some investigators advocate the initiation of highly active antiretroviral therapy (HAART) for this population prior to the initiation of HCV therapy. It is postulated that HAART will improve the host immune function by increasing the CD4+ cell count and decreasing HIV viral load, thought to be advantageous for patients starting HCV therapy. Despite its promising hypothesis, whether HAART ultimately leads to a reduction in HCV load in coinfected persons remains controversial. This is a non-blinded, randomized controlled trial to evaluate the impact of HAART on the immunologic, virologic, and clinical responses to HCV treatment with peginterferon and ribavirin in coinfected individuals with CD4 greater than or equal to 500 cells/mm (3) or greater than or equal to 350 cells/mm(3) and a viral load less than or equal to 40,000 copies/mL. The study will also address the safety and efficacy of administering a combination of HAART along with peginterferon alpha-2b and ribavirin to HIV-infected individuals. 128 patients who are coinfected with HIV and HCV will be recruited for the study and randomized to receive one of two treatment regimens: 1) control group: will be treated with peginterferon alpha-2b and ribavirin for 48 weeks, or 2) experimental group: will be treated with highly active antiretroviral therapy for six months. At that point, they will begin receiving peginterferon alpha-2b and ribavirin at the same doses as the control group for 48 weeks. During the 72-week follow up period, these patients will be monitored for both HCV and HIV viral loads and CD4+ lymphocyte counts. The results of the study will enable us to better delineate the relationship between the immune reconstitution effects induced by HAART and the clinical, immunologic, and virologic responses of coinfected persons treated with peginterferon and ribavirin. In addition, evaluating the safety of coadministering peginterferon, ribavirin, and HAART will further refine the best therapeutic regimen for this patient population.