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Tipranavir is a recently approved nonpeptidic protease inhibitor specifically developed for the management of human immunodeficiency virus (HIV) infection in treatment-experienced patients with protease inhibitor-resistant infection. It is active against a wide range of drug-resistant laboratory- and patient-derived isolates. Tipranavir requires pharmacokinetic boosting by ritonavir (200 mg) to achieve therapeutic levels with twice-daily dosing and must be administered with food for optimal absorption. It is a potent protease inhibitor with a unique drug-resistance profile that offers advantages in the management of cases of multidrug-resistant HIV infection. Tipranavir (in combination with ritonavir) is both an inhibitor and inducer of cytochrome p450, with significant potential for drug-drug interactions, and therefore, it must be used cautiously when administered to patients who are receiving other drugs. Evolution of drug resistance after treatment failure with tipranavir is complex and is not yet fully understood. There is limited overlap in the resistance mutations that predict response to tipranavir and another new protease inhibitor, darunavir, which is active against drug-resistant isolates. Tipranavir is associated with elevations in alanine aminotransferase and aspartate aminotransferase levels, as well as elevated cholesterol and triglyceride levels, and can cause the typical gastrointestinal adverse effects associated with all protease inhibitors.
Saravolatz et al. (Tue,) studied this question.