title: Performance of six different ritonavir-boosted protease inhibitor-based regimens in heavily antiretroviral-experienced HIV-infected patients.
abstract: BACKGROUND
  Regimens based on ritonavir-boosted protease inhibitors (PI/r) are often used as rescue interventions. It is unclear whether significant differences exist between distinct PI/r.
  
  
  METHODS
  All HIV+ patients who had experienced PI failure at two HIV clinics and were rescued with a regimen based on saquinavir (SQV)/r 1000/100 mg bid, indinavir (IDV)/r 800/100 mg bid, lopinavir (LPV)/r 400/100 mg bid, amprenavir (APV)/r 600/100 mg bid, atazanavir (ATV)/r 300/100 mg qd, or tipranavir (TPV)/r 500/200 mg bid were retrospectively examined. A significant virological response (VR) was defined as >1 log reduction in plasma HIV-RNA or to <50 copies/mL at week 24.
  
  
  RESULTS
  A total of 389 patients were included in the analysis: 139 on SQV/r, 35 on IDV/r, 129 on LPV/r, 35 on APV/r, 29 on ATV/r, and 22 on TPV/r. No significant differences in HIV-RNA and CD4 counts at baseline were recognized between groups. In a multivariate analysis, only the total number of protease resistance mutations was associated with a lower VR (odds ratio [OR] = 0.77, 95% CI 0.68-0.87, p < .001). The presence of <5 or > or =5 protease resistance mutations at baseline was the best threshold to discriminate the achievement of VR in any treatment group. In an intent-to-treat analysis, for individuals with 5 protease resistance mutations, the rates of VR were 64% with TPV/r, 47% with LPV/r, 46% with SQV/r, 33% with ATV/r, 25% with IDV/r, and 16% with APV/r. Adverse events leading to treatment withdrawal occurred more frequently using IDV/r (22.8%) than others (p = .03).
  
  
  CONCLUSIONS
  The rate of VR in salvage therapy using PI/r-based regimens is relatively high in PI-experienced patients. The efficacy is greatly influenced by the number of baseline protease resistance mutations; 5 mutations is the best threshold to predict the chances of VR to any PI/r-based regimen.
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Mendoza
authors.forename: Luisa
authors.initials: L
authors.lastname: Valer
authors.forename: Esteve
authors.initials: E
authors.lastname: Ribera
authors.forename: Pablo
authors.initials: P
authors.lastname: Barreiro
authors.forename: Luz
authors.initials: L
authors.lastname: Martín-Carbonero
authors.forename: German
authors.initials: G
authors.lastname: Ramirez
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D002219:Carbamates / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005663:Furans; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000009:adverse effects / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009842:Oligopeptides / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011744:Pyrimidinones / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D019438:Ritonavir / Q000627:therapeutic use; D016879:Salvage Therapy; D019258:Saquinavir / Q000627:therapeutic use; D013030:Spain; D013449:Sulfonamides / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D012367:RNA, Viral; D013449:Sulfonamides; D061466:Lopinavir; D000069446:Atazanavir Sulfate; C095108:amprenavir; D019469:Indinavir; D019258:Saquinavir; D019438:Ritonavir