Tipranavir inhibits broadly protease inhibitor-resistant HIV-1 clinical samples

Although the use of HIV-1 protease inhibitors (PI) has substantially benefited HIV-1-infected individuals, new PI are urgently needed, as broad PI resistance and therapy failure is common. The antiviral activity of tipranavir (TPV), a non-peptidic PI, was assessed in in vitro culture for 134 clinical isolates with a wide range of resistance to currently available peptidomimetic PI. The susceptibility of all 134 variants was then re-tested with the four PI simultaneously with TPV, using the Antivirogram assay. Of 105 viruses with more than tenfold resistance to three or four PI and an average of 6.1 PI mutations per sample, 95 (90%) were susceptible to TPV; eight (8%) had four- to tenfold resistance to TPV and only two (2%) had more than tenfold resistance. The substantial lack of PI cross-resistance to TPV shown by highly PI-resistant clinical isolates makes TPV an attractive new-generation HIV inhibitor.