Non-peptidic protease inhibitors (NPPIs): Tipranavir

Mayers, Douglas L.; Curry, Kevin; Kohlbrenner, Veronika; McCallister, Scott

doi:10.1016/s1075-8593(03)04003-6

Cited by 2 publications

(3 citation statements)

References 11 publications

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“…Tipranavir is a novel, nonpeptidic inhibitor of the HIV-1 protease manufactured by Boehringer-Ingelheim Pharmaceuticals, Inc. Tipranavir's antiviral activity was evaluated with several cell culture systems and against clinical HIV-1 strains, and it was found to be a potent inhibitor of wild-type HIV-1 replication, with 50% inhibitory concentrations (IC 50 s) ranging from 0.03 to 0.07 M and 90% inhibitory concentrations ranging from 0.07 to 0.18 M (1,12,17,19). In vitro passage studies showed that the development of resistance to tipranavir is slow, requiring up to 9 months in culture (5).…”

Section: Current Treatment Of Human Immunodeficiency Virus (Hiv)mentioning

confidence: 99%

Genotypic Changes in Human Immunodeficiency Virus Type 1 Protease Associated with Reduced Susceptibility and Virologic Response to the Protease Inhibitor Tipranavir

Baxter

Schapiro

Boucher

et al. 2006

J Virol

115

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determine if the same mutations would be selected and to assess how these mutations contribute to multiple-regression models of tipranavir-related phenotype and of virologic response. A tipranavir mutation score was developed from these analyses, which consisted of a unique string of 16 protease positions and 21 mutations (10V, 13V, 20M/R/V, 33F, 35G, 36I, 43T, 46L, 47V, 54A/M/V, 58E, 69K, 74P, 82L/T, 83D, and 84V). HIV-1 isolates displaying an increasing number of these tipranavir resistance-associated mutations had a reduced phenotypic susceptibility and virologic response to tipranavir. Regression models for predicting virologic response in phase III trials revealed that each point in the tipranavir score was associated with a 0.16-log 10 copies/ml-lower virologic response to tipranavir at week 24 of treatment. A lower number of points in the tipranavir score and a greater number of active drugs in the background regimen were predictive of virologic success. These analyses demonstrate that the tipranavir mutation score is a potentially valuable tool for predicting the virologic response to tipranavir in protease inhibitor-experienced patients.

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Section: Current Treatment Of Human Immunodeficiency Virus (Hiv)mentioning

confidence: 99%

Genotypic Changes in Human Immunodeficiency Virus Type 1 Protease Associated with Reduced Susceptibility and Virologic Response to the Protease Inhibitor Tipranavir

Baxter

Schapiro

Boucher

et al. 2006

J Virol

115

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“…In vitro, tipranavir (8) exhibits significant activity against multiple PI-resistant clinical isolates and high-level resistance tends to map to unique mutations at codons not previously observed with other PIs [12][13][14][15][16]. The efficacy of tipranavir (8), administered in a self-emulsifying drug delivery system with and without ritonavir in drug treatmentnaïve HIV-1-infected patients was disclosed, and the RESIST trials demonstrated significant antiviral activity in heavily treatment-experienced patients [12,13,16,17].…”

Section: Clinical Developments With Hiv Drugsmentioning

confidence: 99%

“…An analysis of 1226 envelope sequences from HIV subtypes A-G, that focused on the frequency with which mutations conferring reduced sensitivity to BMS-378806 (11) occurred, anticipated that genotypic background resistance will be more prevalent in non-B subtypes [96]. The first clinical efficacy data for this class of gp120-CD4 inhibitor was reported in 2004 with results from a phase IIa study with BMS-488043 (12) [97]. In this trial, 7 of 12 patients administered 800 mg of BMS-488043 (12) BID as monotherapy for 8 days experienced at least a 1 log 10 decline in viral load, with 3 of 12 experiencing a >1.5 log 10 reduction [97].…”

Section: Inhibitors Of Hiv Entry Hiv Attachment Inhibitorsmentioning

confidence: 99%

Developments in Antiviral Drug Design, Discovery and Development in 2004

Meanwell

Belema²,

Carini³

et al. 2005

CDTID

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This article summarizes key aspects of progress made during 2004 toward the design, discovery and development of antiviral agents for clinical use. Important developments in the identification, characterization and clinical utility of inhibitors of human immunodeficiency virus; the hepatitis viruses, hepatitis B, hepatitis C; the herpes family of viruses, herpes simplex viruses 1 and 2, varicella zoster virus, Epstein-Barr virus and human cytomegalovirus; the respiratory viruses, influenza, respiratory syncytial virus, human metapneumovirus, picornaviruses, measles and the severe acute respiratory syndrome coronavirus; human papilloma virus; rotavirus; Ebola virus and West Nile virus, are reviewed.

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Non-peptidic protease inhibitors (NPPIs): Tipranavir

Cited by 2 publications

References 11 publications

Genotypic Changes in Human Immunodeficiency Virus Type 1 Protease Associated with Reduced Susceptibility and Virologic Response to the Protease Inhibitor Tipranavir

Genotypic Changes in Human Immunodeficiency Virus Type 1 Protease Associated with Reduced Susceptibility and Virologic Response to the Protease Inhibitor Tipranavir

Developments in Antiviral Drug Design, Discovery and Development in 2004

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