title: Efficacy of protease inhibitor monotherapy vs. triple therapy: meta-analysis of data from 2303 patients in 13 randomized trials.
abstract: OBJECTIVE
  The aim of this analysis was to review the evidence and update a meta-analysis evaluating the efficacy and safety results from randomized controlled trials of ritonavir-boosted protease inhibitor (PI/r) monotherapy.
  
  
  METHODS
  A PubMed/EMBASE search was conducted to find randomized trials of PI/r monotherapy vs. triple therapy in patients with HIV-1 RNA suppression at baseline (<50 HIV-1 RNA copies/mL). Rates of virological suppression were analysed using switch-equals-failure and intensification-included endpoints [intent-to-treat (ITT)]. The rate of treatment-emergent resistance mutations, neurocognitive function endpoints, and cerebrospinal fluid (CSF) HIV-1 RNA were also analysed by treatment arm.
  
  
  RESULTS
  There were 2303 patients from 13 different randomized clinical trials of darunavir/r monotherapy (n = 784: MONET, MONOI, Monarch and PROTEA), lopinavir/r monotherapy (n = 829: OK pilot, OK-04, KalMo, KALESOLO, KRETA, MOST and DREAM), atazanavir/r monotherapy (n = 103: MODAT), or all three (n = 587: PIVOT). HIV-1 RNA plasma suppression was lower in the PI/r monotherapy arm compared with the triple therapy arm in the switch-equals-failure analysis [difference -8.3%; 95% confidence interval (CI) -11.9 to -4.8%], but not when intensification was included (difference 0.5%; 95% CI -2.5 to 3.6%). Rates of resistance mutations were similar between arms, as was overall neurocognitive function.
  
  
  CONCLUSIONS
  PI/r monotherapy showed a higher risk of plasma HIV-1 RNA elevations. However, there was no increased risk of treatment-emergent drug resistance, neurocognitive endpoints did not differ, and HIV-1 RNA suppression rates after intensification were similar between PI/r monotherapy and triple therapy.
authors.affiliation: IdiPAZ, La Paz Hospital, Madrid, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: Arribas
authors.affiliation: Department of Infectious and Tropical Diseases, Saint Antoine Hospital, AP-HP, and INSERM UMR S 1136, Paris, France.
authors.forename: P-M
authors.initials: PM
authors.lastname: Girard
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore.
authors.forename: N
authors.initials: N
authors.lastname: Paton
authors.affiliation: Department of Medicine, Imperial College, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Winston
authors.affiliation: Virology, AP-HP, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, UPMC University of Paris 06, UMR S 1136, Paris, France.
authors.forename: A-G
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: AIDS Centre, Kaplan Medical Centre, Rehovot, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Elbirt
authors.affiliation: Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Hill
authors.affiliation: EMEA, Janssen, Issy-les-Moulineux, France.
authors.forename: M B
authors.initials: MB
authors.lastname: Hadacek
mesh_terms: D000069446:Atazanavir Sulfate / Q000627:therapeutic use*; D002555:Cerebrospinal Fluid / Q000821:virology; D000069454:Darunavir / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D019438:Ritonavir / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D019438:Ritonavir; D000069454:Darunavir
keywords: darunavir; lopinavir; monotherapy; protease inhibitor