Treatment of Hepatitis C in HIV-Infected Patients

Abstract

IN THE MODERN ERA OF HIGHLY ACTIVE ANTIRETROVIRAL therapy (HAART), hepatitis C virus (HCV) has emerged as a major cause of morbidity and death in human immunodeficiency virus (HIV) infection. An estimated 15% to 30% of HIV-infected individuals are coinfected with HCV, representing 150000 to 300000 patients in the United States alone. The prevalence of anti-HCV antibodies in HIVinfected persons differs significantly according to the HIVexposure risk category, ranging from less than 10% in homosexual men to more than 85% in injecting drug users. In the vast majority of immunocompetent non–HIVinfected persons, chronic hepatitis C usually takes a relatively mild course, leading to liver cirrhosis in 2% to 25% after 20 to 25 years depending on the individual risk factor profile. Liver-related death is only slightly more frequent in HCV-infected individuals. In contrast, hepatitis C may take a much more severe course in HIV-infected patients. In men with hemophilia, the prevalence of cirrhosis as well as liver-related deaths is significantly higher in HCV-HIV– coinfected individuals than in patients infected with HIV alone. However, these findings may not necessarily reflect the situation in other cohorts in which HCV infection has not been shown to increase the risk of death. Since antiretroviral therapy can be associated with significant hepatotoxicity, there has been some concern that HAART, specifically protease inhibitors, may promote progression of fibrosis in HCV-RNA–positive patients. Fortunately, this has not been the case, and antiretroviral therapy has even been shown to reduce long-term liver-related mortality in HIV-HCV–coinfected patients. In contrast, HCV infection appears to influence the natural history of HIV disease. In the Swiss HIV cohort, among more than 3000 HIVinfected individuals, those also infected with HCV had a modestly increased risk for developing AIDS and a less robust increase in CD4 cell counts after initiation of antiretroviral therapy compared with patients infected with HIV alone. On the other hand, a study from Baltimore found that HCV coinfection had no influence on developing AIDS or response to HAART. These differences highlight the problem that different cohorts may be difficult to compare because both HIV and HCV disease may have different trajectories depending on the route of infection (eg, blood transfusions vs community acquired) and other factors. Interactions between HCV and HIV are difficult to investigate. Although the primary site of replication differs (for HCV, the liver; for HIV, T cells, monocytes, and dendritic cells), HCV may also replicate in dendritic cells and monocytes, while HIV can cause hepatitis. Thus, both viruses may directly interact with the other’s replication and influence the host’s immune response to the other virus. Hepatitis C virus replication is much more rapid in HIV-infected patients than in patients infected with HCV alone, indicating decreased immune function. On the other hand, HCV proteins may directly inhibit the function of dendritic cells and natural killer cells and thus alter the anti-HIV–specific immune response. Thus, coinfection with HIV and HCV may influence viral load and immune responses and thereby affect efficacy of antiviral treatment against both HIV and HCV. Treatment options for patients infected with hepatitis C have significantly improved only in recent years. Acute hepatitis C as well as chronic HCV genotype 2 or 3 infection is now considered a curable disease in immunocompetent patients. Even patients infected with the more difficult-to-treat HCV genotypes 1 and 4 can achieve sustained clearance rates of HCV-RNA in about 50%. Three