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Pedro Cahn, Jorge Villacian, Adriano Lazzarin, Christine Katlama, Beatriz Grinsztejn, Keikawus Arasteh, Paulo López, Nathan Clumeck, Jan Gerstoft, Nikolas Stavrianeas, Santiago Moreno, Francisco Antunes, Dietmar Neubacher, Douglas Mayers, Ritonavir-Boosted Tipranavir Demonstrates Superior Efficacy to Ritonavir-Boosted Protease Inhibitors in Treatment-Experienced HIV-Infected Patients: 24-Week Results of the RESIST-2 Trial, Clinical Infectious Diseases, Volume 43, Issue 10, 15 November 2006, Pages 1347–1356, https://doi.org/10.1086/508352
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Abstract
Background. Tipranavir, a novel protease inhibitor, has demonstrated antiviral activity against protease inhibitor—resistant human immunodeficiency virus type 1 (HIV-1) isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-2) trial is an ongoing, open-label, phase III trial comparing ritonavir-boosted tipranavir (TPV/r) plus an optimized background regimen with an individually optimized, ritonavir-boosted protease inhibitor in treatment-experienced, HIV-1-infected patients.
Methods. Patients at 171 sites in Europe and Latin America who had received ⩾2 previous protease inhibitor regimens, had triple-antiretroviral class experience, had an HIV-1 RNA level ⩾1000 copies/mL, and had genotypically demonstrated primary protease inhibitor resistance were eligible. After genotypic resistance tests were performed, a protease inhibitor and optimized background regimen were selected before randomization. Patients were randomized to receive either TPV/r or comparator protease inhibitor—ritonavir (CPI/r) and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed HIV-1 load reduction ⩾1 log10 less than the baseline value without a treatment change at week 24.
Results. A total of 863 patients were randomized and treated. At baseline, the mean HIV-1 load was 4.73 log10 copies/mL, and the mean CD4+ cell count was 218 cells/mm3. The preplanned 24-week efficacy analyses of 539 patients demonstrated treatment response rates of 41% in the TPV/r arm and 14.9% in the CPI/r arm (intent-to-treat analysis; P < .0001). The mean CD4+ cell count increased by 51 cells/mm3 in the TPV/r arm and by 18 cells/mm3 in the CPI/r arm. The most common adverse events were mild-to-moderate diarrhea, nausea, and headache. Grade 3 or greater elevations in serum transaminase, cholesterol, and triglyceride levels were more frequent in the TPV/r arm.
Conclusions. TPV/r had superior antiviral activity and increased immunologic benefits, compared with CPI/r, at week 24 among treatment-experienced patients infected with multidrug-resistant HIV-1.
- hiv
- triglycerides
- cholesterol
- diarrhea
- headache
- antiviral agents
- cell count
- phase 3 clinical trials
- genotype
- hiv-1
- latin america
- nausea
- protease inhibitor
- ritonavir
- transaminases
- arm
- enfuvirtide
- rna
- hiv infections
- anti-retroviral agents
- tipranavir
- frequency of responses
- baseline value
- resist trials
- immunology
- adverse event
- treatment modification
