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).

Author(s): Walmsley SL, Katlama C, Lazzarin A, Aresteh K, Pierone G, Blick G, Johnson M, Meier U, Macgregor TR, Leith JG

Affiliation(s): From the *Division of Clinical Investigation and Human Physiology, University of Toronto, Toronto, Ontario, Canada; daggerDepartment of Infectious Diseases, Hopital Pitie-Salpetriere, Paris, France; double daggerInfectious Diseases Department, Universita Vita-Salute San Raffaele, Milan, Italy; section signEPIMED c/o Vivantes Auguste-Viktoria-Hospital, Berlin, Germany; parallelTreasure Coast Infectious Disease Consultants, Vero Beach, FL; paragraph signCircle Medical, Norwalk, CT; #HIV/AIDS Department, Royal Free Hospital, London, United Kingdom; **Boehringer Ingelheim, Ingelheim, Germany; daggerdaggerBoehringer Ingelheim, Ridgefield, CT; and double daggerdouble daggerBoehringer Ingelheim, Burlington, Ontario, Canada.

Publication date & source: 2008-04-01, J Acquir Immune Defic Syndr., 47(4):429-440.

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.