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

Objective: Although the use of HIV-1 protease inhibitors (PI) has substanti ally benefited HIV-1-infected individuals, new PI are urgently needed, as b road PI resistance and therapy failure is common. Methods: The antiviral activity of tipranavir (TPV), a non-peptidic PI, was assessed in in vitro culture for 134 clinical isolates with a wide range o f resistance to currently available peptidomimelic PI. The susceptibility o f all 134 variants was then re-tested with the four PI simultaneously with TPV, using the Antivirogram(TM) assay. Results: 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. Conclusions: The substantial lack of PI cross-resistance to TPV shown by hi ghly PI-resistant clinical isolates makes TPV an attractive new-generation HIV inhibitor. (C) 2000 Lippincott Williams & Wilkins.