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Genotypic susceptibility to tipranavir (TPV) and darunavir (DRV) in a cohort of treatment-experienced patients (TEP)

Purpose of the study

TPV and DRV are ritonavir-boosted HIV protease inhibitors (PI) indicated for use in TEPs with PI resistance. Both agents have shown superior virologic and immunologic responses in TEPs compared with first-generation PIs. In the Utilization of HIV Drug Resistance in Treatment-Experienced Patients (UTILIZE) study, we assessed the presence of resistance to tipranavir, darunavir, and other antiretroviral agents among HIV-1 isolates in treatment-experienced patients.

Methods

UTILIZE was an observational study at 40 US sites that examined clinician use of HIV drug-resistance testing in TEPs failing a PI-based regimen. Patients were randomized to have either a genotype (GT; Monogram GeneSeq) or combined phenotype-genotype test (PGT; Monogram Phenosense GT) to assist with treatment decision-making. For this analysis, only genotypic resistance data were evaluated to assess PI cross-resistance.

Summary of results

246 patients enrolled and 236 had resistance testing, of whom 139 (59%) had evidence of HIV-1 resistance to at least one PI. Median HIV-RNA and CD4 count were 30,538 copies/mL and 197 cells/mm3, with no significant differences between GT and PGT groups. Of the 139 patients with evidence of PI resistance, 28% of isolates were resistant to all PIs; 58% and 55% remained sensitive to TPV and DRV, respectively. In contrast, isolate susceptibility to indinavir, lopinavir, atazanavir, saquinavir, or nelfinavir was 21.6%, 20.1%, 19.4%, 16.5%, and 7.9%, respectively. TPV-DRV discordance rates were similar: 15.1% TPV sensitive/DRV resistant and 12.2% TPV resistant/DRV sensitive. 50% (7/14) of isolates from TEPs failing TPV remained sensitive to TPV, while 3% (1/29) of isolates from TEPs failing DRV remained sensitive to DRV.

Conclusion

In this cohort of TEPs failing a PI-based regimen, 59% of HIV-1 isolates demonstrated PI resistance. Of these isolates, over 50% remained sensitive to either TPV or DRV, with 27.3% sensitive to only one of the two drugs. In PI-experienced patients, TPV and DRV remain the most likely available PIs to use in constructing a new regimen.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Baxter, J., Bhatti, L., Scherer, J. et al. Genotypic susceptibility to tipranavir (TPV) and darunavir (DRV) in a cohort of treatment-experienced patients (TEP). JIAS 11, P192 (2008). https://doi.org/10.1186/1758-2652-11-S1-P192

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  • DOI: https://doi.org/10.1186/1758-2652-11-S1-P192

Keywords

  • Indinavir
  • Saquinavir
  • Nelfinavir
  • Atazanavir
  • Lopinavir