Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure.

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Hsieh SM, Chang SY, Hung CC, Sheng WH, Chen MY, Chang SC

Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure.

BMC Infect Dis. 2009 Sep 14;9:154. doi: 10.1186/1471-2334-9-154.

PubMed ID

19751502 [ View in PubMed

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Abstract

BACKGROUND: Tipranavir (TPV) is a recently approved nonpeptidic protease inhibitor (PI) of HIV-1 and has been indicated for those infected with PIs-resistant HIV-1. However, in clinical practice, whether the HIV-1 from the patients with virological failure to the regimens containing first-line PIs remains susceptible to TPV/r may be questionable. METHODS: To assess the resistance levels to TPV of HIV-1 from patients with treatment failure to first-line PIs, patients who experienced virological failure were tested for genotypic resistance of HIV-1 since August 2006 in National Taiwan University Hospital. Patients were enrolled for this analysis if their failed regimens contained > 12 weeks of atazanavir or lopinavir/ritonavir (defined as ATV group and LPV/r group, respectively), but were excluded if they experienced both or other PIs. The levels of genotypic resistance to TPV/r were determined by TPV mutation score. RESULTS: Till May 2008, 21 subjects in ATV group and 20 subjects in LPV/r group were enrolled. The TPV mutation scores in subjects in LPV/r group were significantly higher than these in ATV group (median, 3 vs 1, P = 0.007). 95.2% subjects in ATV group and only 45% subjects in LPV/r group had an estimated maximal virological response to TPV/r (P < 0.001). The resistance levels to TPV/r correlated with the duration of exposure to first-line PIs, whether in ATV or LPV/r group. CONCLUSION: Cross-resistance from first-line PIs may impede the effectiveness of TPV/r-containing salvage therapy. TPV/r should be used cautiously for patients with virological failure to LPV/r especially long duration of exposure.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tipranavir	Human immunodeficiency virus type 1 protease	Protein	Human immunodeficiency virus 1	Yes	Inhibitor	Details