Tipranavir is a novel nonpeptidic protease inhibitor (PI) with activity against wild-type and multidrug-resistant HIV-1 both in vitro and in HIV-infected patients. Tipranavir/ritonavir 500 mg/200 mg administered twice daily for 3 weeks to healthy volunteers produced a median (range) maximum plasma concentration and minimum plasma concentration of 79.1 (34.9-111.7) mg/L and 19.5 (0.43-42.8) mg/L, respectively. Concomitant administration with low-dose ritonavir significantly increases tipranavir plasma concentrations; therefore, the recommended dose is tipranavir 500 mg and ritonavir 200 mg twice daily. Tipranavir is a substrate and inducer of cytochrome P450 3A4 isoenzyme, thus is predisposed to interactions with other agents that are substrates, inducers or inhibitors of this enzyme family. Significant drug-drug interactions have been reported with co-administration of tipranavir/ritonavir and other PIs but not with the non-nucleoside reverse transcriptase inhibitors, efavirenz and nevirapine. Tipranavir/ritonavir 500 mg/200 mg twice daily in combination with an optimised background regimen was more effective than a ritonavir-boosted comparator PI plus an optimised background regimen. The adverse effect profile for tipranavir is similar to other boosted PI regimens and most commonly includes gastrointestinal complaints. Severe adverse events that require close monitoring include hepatotoxicity and lipid abnormalities. Tipranavir retains activity in many highly treatment-experienced patients with a large number of protease mutations. Therefore, this novel PI in combination with ritonavir represents an important new choice in the treatment of multiple-PI-experienced patients.