Tipranavir: the first nonpeptidic protease inhibitor for the treatment of protease resistance.
BACKGROUND
Despite the availability of a growing number of potent antiretroviral agents, efforts to completely suppress viral replication in patients with HIV-1 infection are limited because of the increasing risk of resistance. Tipranavir (TPV) is the first in a class of antiretroviral agents known as nonpeptidic protease inhibitors (PIs). TPV exhibits a resistance profile distinct from that of other currently available PIs, making it a potential option for treatment experienced patients with resistance to multiple Pls.


OBJECTIVE
This article discusses the clinical pharmacology and efficacy of TPV in the treatment of HIV-1 infection in patients who are highly treatment experienced or harbor PI-resistant virus.


METHODS
A search was conducted of English language, peer-reviewed articles and abstracts indexed on the MEDLINE and Current Contents databases (1966-May 2007) using the terms tipranavir, Aptivus, nonpeptidic protease inhibitor, human immunodeficiency virus, and protease resistance. Product information and abstracts from national and international AIDS and retrovirus meetings (2005-2006) were also reviewed.


RESULTS
Use of TPV in combination with ritonavir (TPV/r) was approved by the US Food and Drug Administration based on 2 Phase III studies. In these studies, HIV-infected patients with extensive treatment experience with antiretroviral agents, including PIs, nucleoside analogues, and nonnucleoside reverse transcriptase inhibitors, were randomized to receive TPV/r or a ritonavir-boosted comparator PI. All patients had evidence of resistance to multiple PIs. The specific comparator (amprenavir, indinavir, lopinavir, or saquinavir) was selected for each patient with the aid of resistance testing. Each patient also received an optimized background regimen of antiretroviral agents, which could include enfuvirtide. At 24, 48, and 96 weeks, the TPV/r group had higher rates of virologic response (defined as > or =1 log10 decrease in HIV RNA) and viral suppression (to <400 and <50 copies/mL) than did the comparator group.


CONCLUSIONS
Although TPV has a mechanism of action similar to that of earlier-generation PIs, it has activity against HIV-1 strains with resistance to multiple PIs. Currently, TPV/r is indicated for use in highly treatment experienced patients with multiple PI resistance.
D000328:Adult; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011753:Pyrones / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013449:Sulfonamides
D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; C107201:tipranavir