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

Research output: Contribution to journalArticlepeer-review


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
Issue number2
Publication statusPublished - Feb 2007

ASJC Scopus subject areas

  • Immunology
  • Virology


Dive into the research topics of 'Efficacy and safety of three doses of tipranavir boosted with ritonavir in treatment-experienced HIV type 1-infected patients'. Together they form a unique fingerprint.

Cite this