Journal
DRUGS
Volume 63, Issue 15, Pages 1611-1618Publisher
ADIS INT LTD
DOI: 10.2165/00003495-200363150-00009
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Tipranavir is a potent and selective non-peptidic HIV-1 protease inhibitor with a markedly improved resistance profile compared with traditional, peptidomimetic protease inhibitors. The presence of five or fewer protease gene mutations or one or two protease inhibitor resistance-associated mutations (PRAMs) is associated with reduced susceptibility to currently available protease inhibitors. However, 16-20 mutations (including three or more PRAMs) may be needed to confer resistance to tipranavir. Tipranavir-based therapy achieved sustained viral suppression for more than 48 weeks in a small phase 11 trial in multiple protease inhibitor-experienced HIV-infected patients. A large dose-finding study demonstrated potent virological reduction through 14 days of functional monotherapy in heavily pretreated HIV-infected patients with 6 to >20 protease gene mutations at baseline. Two large, ongoing, phase III trials in patients with multi-drug resistant HIV infection are comparing the efficacy of tipranavir/ritonavir 500/200mg twice daily plus a patient-individualised background antiretroviral regimen versus other ritonavir-boosted protease inhibitor regimens. In general, tipranavir has been well tolerated in clinical trials. As with other protease inhibitors, the most common adverse events with tipranavir have been gastrointestinal disturbances.
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