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Increased use of tests for HCV that were first FDA- approved in 1990

Fewer deaths now due to AIDS- related opportunistic infections (because of improved immunity from HAART and/or effects from preventive antibiotic therapy)
Other drugs in HAART regimens that might cause liver toxicity
The “cohort effect” from the late 70s (if people who were later to become infected with HIV actually became infected with HCV in the late 70s, then many liver-related deaths could be accounted for by the normal delay of 20 to thirty years before liver complications are detected)

Whatever the underlying cause of the HAART-liver deaths connection, the reports all show that, at least in 1997, liver disease became fatal for a tenth of HIV-positive people. This percentage is expected to increase, and will certainly do so if better screening for HCV is not forthcoming.16

Since research shows HAART to be associated with liver disease so regularly, HAART treatment has become an independent risk factor for liver toxicity. Although estimates vary, it is clear that at roughly 15% of HAART patients will develop hepatotoxicity. While there is some controversy about when to treat with HAART in coinfected individuals, after HCV treatment or right away, it is generally recognized that rigorous drug monitoring for liver toxicity is extremely important.

Current treatment options for HCV
The standard of care for treating HCV is alpha interferon (Intron A, Roferon, and Wellferon) with ribavirin. Ribavirin, a guanosine analog, is an older drug that has been around for 20 to 25 years. It inhibits replication in a range of viruses under test-tube conditions, but its antiviral action against HCV and its effect on the immune response are still poorly understood. Ribavirin produces anemia and other side effects, may interact in complex ways with certain antiretroviral medications, and may be poorly tolerated if kidney disease is present.3,17

Interferons are natural cellular proteins that can protect cells against viruses; the mechanism of action is thought to be immune regulation.3

Interferon alpha must be injected frequently. The pharmacokinetics of interferon alpha are very poor, which means that the agent is cleared from the bloodstream too quickly to be truly effective in fighting HCV. Its half-life-the amount of time it takes until only half of the original concentration of alpha interferon remains-is so short that a person would need to inject it once a day in order to maintain fully therapeutic blood levels. During the last 12 hours of the usual 2-day dosing interval, in fact, the form of interferon alpha that is currently prescribed is not even detectable in the bloodstream.

The fact that most patients in the U.S. are taking interferon alpha three times a week, and not once a day, helps to explain why this current standard of care does not lead to widespread eradication of HCV disease.

Currently available alpha interferon is associated with anemia and a higher than 5% decrease in CD4+ counts. Side effects include flulike symptoms such as fatigue, fever, and headache, gastrointestinal symptoms, depression, neutropenia (a decrease in white blood cells called neutrophils), and thrombocytopenia (a decreased number of blood platelets).13

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