Aptivus (tipranavir), is a non-peptide protease inhibitor. The drug disrupts the formation of mature viral particles by disrupting synthesis of viral proteins.
Aptivus is specifically indicated as a combination therapy with the approved drug ritonavir, for the treatment of HIV-1-infected adult patients with evidence of viral replication. It is indicated as a second line or later therapy, for use inpatients who are highly treatment experienced or whose HIV-1 strain has shown resistance to other protease inhibitors.
Aptivus is supplied as an oblong pink gelatin capsule. The recommended dose is 250 mg twice daily in combination with 200 mg ritonavir twice daily. The drug should be administered in combination with food.
Approval of Aptivus was based on 2 ongoing, randomized, controlled, open-label, multicenter phase III clinical trials (RESIST-1 and RESIST-2), which enrolled a combined 1159 triple antiretroviral class experienced patients with experience with at least two prior protease-inhibitor-based antiretroviral regimens, including one failure, and at least one, but not more than two, primary protease gene mutations. Subjects were randomized to receive either Aptivus in combination with 200 mg ritonavir plus an optimum background regimen (OBR), or a control regimen of an approved protease inhibitor (lopinavir, amprenavir, saquinavir or indinavir) in combination with ritonavir plus OBR for 24 weeks. Trial data indicated that Aptivus produced more virological responders than approved protease inhibitors, with 40% of subjects achieving a reduction of HIV-1 RNA of at least 1 log10, vs. 18% for control. Furthermore, fewer individuals on Aptivus experienced virologic failure than approved drugs, with 35% failing to achieve at least a 0.5 log10 drop from baseline and a viral RNA load <100,000 copies by week 8, 12% achieving initial response but rebounding by week 24, and 7% never responding, compared to 59%, 11% and 8% for the control group, respectively. These results indicate that Aptivus may provide superior efficacy compared to other protease inhibitors in second-line-or-later regimens of antiretroviral therapy for HIV-1 infections.
Ongoing Study Commitments
Adverse events associated with the use of Aptivus may include, but are not limited to, the following:
In addition, considerable pharmacokinetic interaction has been noted between Aptivus and a number of other classes of drugs, with significant effect on peak and trough plasma drug concentrations, and on total drug exposure. Some of these interactions can be serious or life-threatening. Patients should discuss potential interactions with their physicians.
Aptivus is a member of the 4-hydroxy-5,6-dihydro-2-pyrone sulfonamide class, with activity as a non-peptide protease inhibitor. The drug has been shown to selectively inhibit virus-specific processing of viral Gag and Gag-pol polyproteins, preventing formation of funtional mature virions.
Kandula VR, Khanlou H, Farthing C. Tipranavir: a novel second-generation nonpeptidic protease inhibitor. Expert Review of Anti-Infective Therapy 2005 Feb;3(1):9-21
Cheonis N. Tipranavir: the first nonpeptidic protease inhibitor. Bulletin of Experimental Treatments for AIDS 2004 Winter;16(2):15-7
Bulgheroni E, Citterio P, Croce F, Lo Cicero M, Vigano O, Soster F, Chou TC, Galli M, Rusconi S. Analysis of protease inhibitor combinations in vitro: activity of lopinavir, amprenavir and tipranavir against HIV type 1 wild-type and drug-resistant isolates. Journal of Antimicrobial Chemotherapy 2004 Mar;53(3):464-8
Larder BA, Hertogs K, Bloor S, van den Eynde CH, DeCian W, Wang Y, Freimuth WW, Tarpley G. Tipranavir inhibits broadly protease inhibitor-resistant HIV-1 clinical samples. AIDS 2000 Sep 8;14(13):1943-8
For additional information regarding Aptivus or HIV-1 infections, please visit the Aptivus web page.