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. 2000 Sep 8;14(13):1943-8.
doi: 10.1097/00002030-200009080-00009.

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

B A Larder  1 , K Hertogs, S Bloor, C H van den Eynde, W DeCian, Y Wang, W W Freimuth, G Tarpley
Affiliations

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

B A Larder et al. AIDS. .

Abstract

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.

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