Efficacy and safety of three doses of tipranavir boosted with ritonavir in treatment-experienced HIV type 1-infected patients

Joseph C. Gathe, Gerald Pierone, Peter Piliero, Keikawus Arasteh, Rafael Rubio, Richard G. Lalonde, David Cooper, Adriano Lazzarin, Veronika M. Kohlbrenner, Catherine Dohnanyi, John Sabo, Douglas Mayers

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Abstract

The efficacy, safety, and pharmacokinetics of three doses of tipranavir/ritonavir (TPV/r) in highly treatment-experienced human immunodeficiency virus (HIV)-1-infected patients with protease inhibitor (PI)-resistant isolates were evaluated. A 24-week multicenter, double-blind, randomized, dose-finding trial was conducted. All patients were three-drug class experienced and had token at least two PI-based regimens. All had at least one primary PI mutation and had plasma HIV-RNA >1000 copies/ml. Patients remained on their background non-PI antiretroviral medications for the first 14 days. After this 14-day period of functional TPV/r monotherapy, the background antiretroviral medications were optimized based on treatment history and the screening genotype. A total of 216 patients were randomized. All groups [TPV/r 500 mg/100 mg (n = 73), 500 mg/200 mg (n = 72), and 750 mg/200 mg (n = 71) twice daily] achieved an approximate 1 log10 reduction in the median HIV-RNA at week 2. A significant reduction was sustained through 24 weeks in the TPV/r 500 mg/200 mg and 750 mg/200 mg groups. The 500 mg/200 mg dose achieved optimal median TPV trough concentrations and lower interpatient variability. The most frequently reported adverse events (AEs) were diarrhea, nausea, vomiting, fatigue, and headache. The TPV/r 750 mg/200 mg group had the highest rate of grade 3 or 4 laboratory abnormalities and study discontinuations due to AEs. All doses of TPV/r tested in this study were associated with HIV-1 viral load reductions through 24 weeks. The 500 mg/200 mg dose achieved the best efficacy, safety, and pharmacokinetic profile in this highly treatment-experienced population and was selected for the pivotal phase 3 studies.

Original languageEnglish
Pages (from-to)216-223
Number of pages8
JournalAIDS Research and Human Retroviruses
Volume23
Issue number2
DOIs
Publication statusPublished - Feb 2007

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ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Gathe, J. C., Pierone, G., Piliero, P., Arasteh, K., Rubio, R., Lalonde, R. G., Cooper, D., Lazzarin, A., Kohlbrenner, V. M., Dohnanyi, C., Sabo, J., & Mayers, D. (2007). Efficacy and safety of three doses of tipranavir boosted with ritonavir in treatment-experienced HIV type 1-infected patients. AIDS Research and Human Retroviruses, 23(2), 216-223. https://doi.org/10.1089/aid.2006.0178