RESUMEN
OBJECTIVE: 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. 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 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. 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 highly PI-resistant clinical isolates makes TPV an attractive new-generation HIV inhibitor.