title: 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.
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 > or = 2 previous protease inhibitor regimens, had triple-antiretroviral class experience, had an HIV-1 RNA level > or = 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 > or = 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.
authors.affiliation: Fundación Huésped, Buenos Aires, Argentina. pcahn@huesped.org.ar
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Jorge
authors.initials: J
authors.lastname: Villacian
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Keikawus
authors.initials: K
authors.lastname: Arasteh
authors.forename: Paulo
authors.initials: P
authors.lastname: López
authors.forename: Nathan
authors.initials: N
authors.lastname: Clumeck
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Nikolas
authors.initials: N
authors.lastname: Stavrianeas
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.forename: Francisco
authors.initials: F
authors.lastname: Antunes
authors.forename: Dietmar
authors.initials: D
authors.lastname: Neubacher
authors.forename: Douglas
authors.initials: D
authors.lastname: Mayers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D011753:Pyrones / Q000494:pharmacology* / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides
chemical_list: D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D019438:Ritonavir; C107201:tipranavir