Pharmacokinetics, safety, and efficacy of tipranavir boosted with ritonavir alone or in combination with other boosted protease inhibitors as part of optimized combination antiretroviral therapy in highly treatment-experienced patients (BI study 1182.51)

Sharon L. Walmsley, Christine Katlama, Adriano Lazzarin, Keikawus Arestéh, Gerald Pierone, Gary Blick, Margaret Johnson, Ulrich Meier, Thomas R. MacGregor, Johnathan G. Leith

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Given the limited treatment options for patients with high-level resistance, antiretroviral (ARV) regimens based on concomitant use of 2 ritonavir (RTV)-boosted protease inhibitors (PIs) were considered a therapeutic option. METHODS: Boehringer Ingelheim (BI) study 1182.51 examined the pharmacokinetic profile, safety, and efficacy of RTV-boosted tipranavir (TPV/r), alone and in combination with comparator PIs (CPIs) in 315 triple-class-experienced, HIV-infected patients. RESULTS: Two weeks after single PI therapy, the addition of TPV/r reduced plasma trough levels 52%, 80%, and 56% for lopinavir (LPV), saquinavir (SQV), and amprenavir (APV) recipients, respectively. After 2 weeks, a TPV/r-only regimen reduced HIV viral load (VL) by a median of 1.06 log10 copies/mL. VL reductions at 2 weeks between single-boosted CPIs were difficult to compare, because the numbers of patients maintaining their previous failing PI after randomization were different. At week 4, patients initiating treatment with TPV-containing regimens sustained VL reduction (median decrease of 1.27 log10 copies/mL). Patients adding TPV to regimens at week 2 achieved median reductions from a baseline of 1.19 log10, 0.96 log10, and 1.12 log10 copies/mL at week 4 in dual-boosted LPV, SQV, and APV groups, respectively. At 24 weeks, VL reductions (median: -0.24 to -0.47 log10 copies/mL) were comparable between treatment groups. CONCLUSIONS: The efficacy of a dual PI regimen depended on the presence of TPV, with additional recycled CPIs having limited activity, even in drug-resistant patient populations with plasma trough concentrations regarded as likely to be adequate in this study. No clear guidelines exist about ARV plasma trough concentrations in treatment-experienced patients, however.

Original languageEnglish
Pages (from-to)429-440
Number of pages12
JournalJournal of Acquired Immune Deficiency Syndromes
Volume47
Issue number4
DOIs
Publication statusPublished - Apr 2008

Keywords

  • Combination antiretroviral therapy
  • Dual-boosted protease inhibitor regimen
  • Nonpeptidic
  • Protease inhibitors
  • Tipranavir

ASJC Scopus subject areas

  • Virology
  • Immunology

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