title: High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial.
abstract: BACKGROUND
  The introduction of 2 or 3 fully active drugs in human immunodeficiency virus (HIV)-infected patients receiving failing antiretroviral therapy is a key determinant of subsequent treatment efficacy. The aim of this study was to assess the safety and efficacy of a regimen containing raltegravir, etravirine, and darunavir/ritonavir for treatment-experienced patients infected with multidrug-resistant HIV.
  
  
  METHODS
  Patients enrolled in this phase II, noncomparative, multicenter trial were naive to the investigational drugs and had plasma HIV RNA levels >1000 copies/mL, a history of virologic failure while receiving nonnucleoside reverse-transcriptase inhibitors (NNRTI), > or =3 primary protease inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) mutations, and < or =3 darunavir and NNRTI mutations. The primary end point was the proportion of patients with plasma HIV RNA levels <50 copies/mL at 24 weeks.
  
  
  RESULTS
  A total of 103 patients enrolled in the study. At baseline, genotypic resistance profiles showed a median of 4 primary protease inhibitor mutations, 1 NNRTI mutation, and 6 NRTI mutations. In addition to the investigational drugs, 90 patients (87%) received optimized background therapy that included NRTIs (86 patients) or enfuvirtide (12 patients). At week 24, 90% of patients (95% confidence interval, 85%-96%) had an HIV RNA level <50 copies/mL. At week 48, 86% (95% confidence interval, 80%-93%) had an HIV RNA level <50 copies/mL. The median CD4 cell count increase was 108 cells/mm(3). Grade 3 or 4 clinical adverse events were reported in 15 patients (14.6%). Only 1 patient discontinued the investigational antiretroviral regimen, because of an adverse event.
  
  
  CONCLUSIONS
  In patients infected with multidrug-resistant virus who have few remaining treatment options, the combination of raltegravir, etravirine, and darunavir/ritonavir is well tolerated and is associated with a rate of virologic suppression similar to that expected in treatment-naive patients.
authors.affiliation: Hôpital Tourcoing, Lille School of Medicine, Lille, France. yyazdan@yahoo.com
authors.forename: Y
authors.initials: Y
authors.lastname: Yazdanpanah
authors.forename: C
authors.initials: C
authors.lastname: Fagard
authors.forename: D
authors.initials: D
authors.lastname: Descamps
authors.forename: A M
authors.initials: AM
authors.lastname: Taburet
authors.forename: C
authors.initials: C
authors.lastname: Colin
authors.forename: B
authors.initials: B
authors.lastname: Roquebert
authors.forename: C
authors.initials: C
authors.lastname: Katlama
authors.forename: G
authors.initials: G
authors.lastname: Pialoux
authors.forename: C
authors.initials: C
authors.lastname: Jacomet
authors.forename: C
authors.initials: C
authors.lastname: Piketty
authors.forename: D
authors.initials: D
authors.lastname: Bollens
authors.forename: J M
authors.initials: JM
authors.lastname: Molina
authors.forename: G
authors.initials: G
authors.lastname: Chêne
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000069454:Darunavir; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011724:Pyridazines / Q000627:therapeutic use; D011743:Pyrimidines; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D011760:Pyrrolidinones; D013449:Sulfonamides; C451734:etravirine; D000068898:Raltegravir Potassium; D019438:Ritonavir; D000069454:Darunavir