Tipranavir: a new protease inhibitor for the treatment of antiretroviral-experienced HIV-infected patients.
Tipranavir (TPV) is a novel non-peptidic protease inhibitor (PI). It binds strongly and selectively to the HIV-1 protease, is orally administered twice daily, boosted with low doses of ritonavir, and shows a favourable resistance profile. In the two registrational trials, named RESIST 1 and 2, TPV/ritonavir 500/200 mg b.i.d., along with an optimised antiretroviral backbone, provided better virologic responses than controls receiving standard of care ritonavir-boosted PI-based regimens. A total of 21 mutations at 16 protease codons have been shown to impact on TPV susceptibility and response rates. The TPV mutation score includes L10V, I13V, K20M/R/V, L33F, E35G, M36I, K43T, M46L, I47V, I54A/M/V, Q58E, H69K, T74P, V82L/T, N83D and I84V. Viruses containing eight or more of these mutations are generally resistant to the drug. TPV use is associated with an excess of grade 3/4 liver enzyme elevations compared with other ritonavir-boosted PIs, and the potential for drug-drug interactions is relevant and must be considered when prescribing TPV.
de Mendoza
Carmen
C
Department of Infectious Diseases, Hospital Carlos III, c/Sinesio Delgado 10, 28029 Madrid, Spain. cmendoza@teleline.es
Morelló
Judit
J
Garcia-Gascó
Pilar
P
Rodríguez-Novoa
Sonia
S
Soriano
Vincent
V
D002986:Clinical Trials as Topic; D004347:Drug Interactions; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D015498:HIV-2 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009154:Mutation; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011753:Pyrones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D013449:Sulfonamides; D016896:Treatment Outcome
D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D016333:HIV Protease; D019438:Ritonavir; C107201:tipranavir