Tipranavir.
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 II 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.
Plosker
Greg L
GL
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Figgitt
David P
DP
D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009154:Mutation / Q000235:genetics; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011753:Pyrones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013449:Sulfonamides
D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D016333:HIV Protease; C107201:tipranavir