Spotlight: IDSA Conference Update

This year the Infectious Diseases Society of America (IDSA) hosted a seminar at which Drs. Godofsky, Sulkowski, Dieterich, and McGovern all gave lectures pertaining to coinfection and monoinfection with hepatitis C virus (HCV) and HIV. Below are the highlights from this seminar.

HCV affects an estimated four million persons in the United States with a prevalence of approximately 1.8% in the general public. The prevalence of HCV for those incarcerated is much higher. The number of inmates with HCV is approximately 255,000, giving a prevalence of 15%. This risk is not contained within correctional facilities, since those released can transmit HCV to their home communities when they return.

In recent years, the incidence of acute HCV infection in the U.S. has declined, in part to mandatory blood supply screening. The most significant risk factors for HCV transmission include injection drug use, accounting for approximately 60-70% of all new cases of HCV, and sexual transmission, accounting for up to 20% of new cases. The limited number of clinicians treating HCV, approximately 2,200, and limited resources, including time, staff, and education, are inadequate in meeting the needs of the large number of patients who are infected with HCV or with both HCV and HIV.

While HCV and HIV have similar modes of transmission, the efficiency of transmission of each virus is very different. The HCV virus is transmitted primarily through blood, with injection drug use being the leading route of transmission. The leading route of transmission for HIV is unprotected heterosexual contact. Based on the different modes of transmission, both demographic and clinical differences in the HIV/HCV-coinfected and HIV-monoinfected patient can be seen. In outpatient studies, coinfected persons have been found to be more likely to have used injection drugs, to be older, to be nonwhite, to have received less than 12 years of education, and to have undergone care with use of public funds. HIV exacerbates the natural history of HCV; among those infected with HCV, those with concurrent HIV infection are less likely to have cleared infection with HCV than those without HIV infection. HIV infection has also been associated with higher HCV RNA viral load and a more rapid progression of HCV-related liver disease. Accordingly, guidelines have been developed for the management of HCV in HIV-infected persons. These guidelines recommend initial treatment of HCV in HIV-infected persons with pegylated interferon plus ribavirin for 48 weeks. Additionally, HIV/HCV-coinfected persons on HCV treatment should be monitored closely given the high likelihood of adverse effects.

The AIDS Pegasys Ribavirin International Co-Infection Trial (APRICOT) evaluated the efficacy and safety of pegylated interferon alfa-2a plus ribavirin (PEG IFN alfa-2a plus RBV) in 868 HIV/HCV coinfected patients. Patients were randomized to one of three 48-week regimens. The overall sustained virologic response (SVR) of 40% was the highest in the regimen including PEG IFN alfa-2a plus RBV, compared to an SVR of 12% and 20%, for regimens excluding ribavirin.

Drug-associated hepatotoxicity has emerged as a major issue in the era of highly active antiretroviral therapy (HAART). In patients infected with HIV, hepatotoxicity can lead to liver-related morbidity, discontinuation of treatment, and death. Drug reactions are classified into two categories: predictable drug reactions, which are often dose-dependent, and unpredictable drug reactions, which are host-dependent and not dose-dependent. Unpredictable drug reactions occur when a drug is converted into a metabolite that is either toxic or acts to provoke some hypersensitivity reaction. Furthermore, unpredictable drug reactions are further classified into immunologic idiosyncratic reactions, such as hypersensitivity reactions accompanied by fever and rash, which occur with a short latency of onset, and idiosyncratic metabolic reactions, characterized by a long latency before onset. Patient vulnerability to liver injury is dependent on the toxification/detoxification processes involved in drug metabolism. Up-regulation of cytochrome P450 (CYP 450) can increase production of certain toxic metabolites. Factors contributing to increased susceptibility to drug-inducted liver disease include age, gender, HIV infection, and alcohol use.

Courtney Colton is IDCR Managing Editor. Disclosures: Nothing to disclose.

Back to the IDCR December 2004 contents page.