New Insights in HIV and Hepatitis C Virus Coinfection

Initial infection with hepatitis C virus (HCV) is characterized by rapid viral replication. Alanine aminotransferase (ALT) levels increase dramatically over the course of the initial 1 to 3 months but may be highly variable thereafter. Following the initial period of viremia, humoral and cellular immune responses develop, but in most cases are insufficient to clear the infection (Liang et al, Ann Intern Med, 2000). HCV has 6 major subtypes; in the United States, approximately 70% of HCV isolates from infected patients are genotype 1. Multiple strains of HCV are present in an individual patient; hence, the virus exists as a quasi species. HCV infection rates based on antibody-positive status in individuals at risk for HIV infection include rates of 70% to 80% in injection drug users and 8% to 10% in men who have sex with men. A recent study in an AIDS Clinical Trials Group population, which was representative of all patients with HIV in the United States, showed an overall HCV seroprevalence rate of 37% (Sherman et al, Clin Infect Dis, 2002). In contrast, studies in volunteer blood donors in the United States indicate a seroprevalence rate of 0.4%. Approximately 80% to 85% of individuals with acute HCV infection develop chronic infection (defined as continuing viral replication). The mechanisms that permit apparent clearance in the 15% to 20% in whom chronic infection is not established remain unclear, although infection with a narrow range of viral quasi species and more vigorous humoral and cellular immune responses may be major factors (Farci and Purcell, Semin Liver Dis, 2000). Over the course of about 20 years, approximately 20% of individuals with chronic infection develop cirrhosis and some patients may progress to death from liver failure or hepatocellular cancer. However, progression appears to be highly variable. In studies of progression to cirrhosis after known exposure, rates have varied from 2.4% over 17 years (in a study of women in Ireland who were infected via contaminated anti-D[RH1] immune globulin) to 32.3% over 7.5 years (in patients in Italy infected via transfusion). Factors associated with poor prognosis for chronic HCV infection include male sex, age at HCV acquisition of more than 40 years, alcohol consumption, iron overload, and immunosuppression (Thomas et al, JAMA, 2000). The incidence of HCV infection dropped dramatically after the mid1980s; the reasons for this decrease remain unclear, although it likely reflects changes in practice in injection drug use. However, the prevalence of chronic infection is increasing and is expected to triple from current rates by about 2015 (Armstrong et al, Hepatology, 2000). This projected increase is of great concern, since the health care system is already stressed at current levels of liver transplantation and expenditures for chronic liver disease. Rational use of HCV diagnostic tests in patient management includes serologic testing and qualitative HCV RNA testing for diagnosis, and liver biopsy for prognosis. ALT level can be quite variable and is not a reliable indicator of severity of disease. Studies in asymptomatic individuals positive for HCV RNA indicate that ALT levels are normal in 31%, increased by less than 2 times the upper limit of normal (ULN) in 42%, and increased by greater than 2 and 3 times the ULN in 15% and 12%, respectively. Similarly, neither the genotypic nor the viral load is an accurate indicator of the degree of histologic injury (Goedert et al, J Infect Dis, 2001). The degree of fibrosis on initial liver biopsy provides important prognostic information; as shown in Figure 1 (Yano et al, Hepatology, 1996), the rate of progression Perspective New Insights in HIV and Hepatitis C Virus Coinfection