Tipranavir (Aptivus)

Published July 13, 2005; Updated October 19, 2011
Susa Coffey, MD
http://hivinsite.ucsf.edu/InSite?page=ar-03-09
Selected References
1. Hicks C, et al. RESIST-1: A Phase 3 Randomized, Controlled, Open-Label Multicenter Trial Comparing Tipranavir/Ritonavir (TPV/r) to an Optimized Comparator Protease Inhibitor/r (CPI/r) Regimen in Antiretroviral (ARV) Experienced Patients: 24-Week Data. In: Program and abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; October 31-November 2, 2004; Washington. Abstract 1137a.
2. Cahn P, et al. 24-week data from RESIST 2: phase 3 study of the efficacy and safety of either tipranavir/ritonavir (TPV/r) or an optimized ritonavir (RTV)-boosted standard-of-care (SOC) comparator PI (CPI) in a large randomized multicenter trial in treatment-experienced HIV+ patients. In: Program and abstracts of the Seventh International Congress on Drug Therapy in HIV Infection; November 14-17, 2004; Glasgow, UK. Abstract PL14.3.
3. Hicks  CB, Cahn  P, Cooper  DA, Walmsley  SL, Katlama  C, Clotet  B, Lazzarin  A, Johnson  MA, Neubacher  D, Mayers  D, Valdez  H; RESIST investigator group.
Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials. Lancet. 2006 Aug;368(9534):466-75
[PubMed ID: 16890833]
Abstract:
BACKGROUND: Treatment options for HIV-1 infected individuals who have received extensive previous antiretroviral therapy are limited. We compared efficacy and safety of the novel non-peptidic protease inhibitor tipranavir co-administered with ritonavir plus an optimised background regimen with that of an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI-ritonavir) in such patients. METHODS: We did a combined analysis of 48-week data from two ongoing, randomised, open-label, multinational, phase III, RESIST studies. HIV-1-infected adults with 3 months or longer previous triple antiretroviral class experience, two or more previous protease inhibitor regimens, HIV-1 RNA 1000 copies per mL or greater, and genotypically demonstrated primary resistance to protease inhibitor, were eligible. Primary endpoints were proportion of treatment responders (with reduction in viral load of 1 log(10) copies per mL or greater below baseline without treatment change) at 48 weeks and time to treatment failure through 48 weeks (intention-to-treat analysis). The RESIST studies are registered with ClinicalTrials.gov, numbers NCT00054717 (RESIST-1) and NCT00144170 (RESIST-2). FINDINGS: 3324 patients were screened; 746 received tipranavir-ritonavir and 737 CPI-ritonavir. 486 (65.1%) patients on tipranavir-ritonavir and 192 (26.1%) on CPI-ritonavir remained on assigned treatment until week 48. At week 48, more patients achieved and maintained treatment response in the tipranavir-ritonavir group than in the CPI-ritonavir group (251 [33.6%] vs 113 [15.3%]; p<0.0001). Median time to treatment failure was significantly longer in the tipranavir-ritonavir group than in the CPI-ritonavir group (113 days vs 0 days; p<0.0001). Gastrointestinal system disorders and raised transaminase, cholesterol, and triglycerides were more frequent in the tipranavir-ritonavir group than in the CPI-ritonavir group. INTERPRETATION: Compared with CPI-ritonavir, tipranavir-ritonavir with an optimised background regimen provides better virological and immunological responses over 48 weeks in patients who have received extensive previous antiretroviral treatment.