title: Effectiveness of protease inhibitor monotherapy versus combination antiretroviral maintenance therapy: a meta-analysis.
abstract: BACKGROUND
  The unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs.
  
  
  METHODS
  We systematically searched Medline, Embase, the Cochrane Library, conference proceedings and trial registries to identify all randomised controlled trials comparing PI/r monotherapy to cART in suppressed patients. We calculated in an intention to treat (loss-of follow-up, discontinuation of assigned drugs equals failure) and per-protocol analysis (exclusion of protocol violators following randomisation) and based on three different definitions for virological failure pooled risk ratios for remaining virologically suppressed.
  
  
  RESULTS
  We identified 10 trials comparing 3 different PIs with cART based on a PI/r plus 2 reverse transcriptase inhibitors in 1189 patients. With the most conservative approach (viral load <50 copies/ml on two consecutive measurements), the risk ratios for viral suppression at 48 weeks of PI/r monotherapy compared to cART were in the ITT analysis 0.94 8 (95% CI 0.89 to 1.00) p = 0.06; risk difference -0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity  = 0.08, I(2) = 43.1%) and in the PP analysis 0.93 ((95%CI 0.90 to 0.97) p<0.001; risk difference -0.07 (95%CI -0.10 to -0.03) p<0.001, p for heterogeneity  = 0.44, I(2) = 0%). Reintroduction of cART in 44 patients with virological failure led in 93% to de-novo viral suppression.
  
  
  CONCLUSIONS
  Virologically well suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from cART to PI/r monotherapy. Failing patients achieve high rates of de-novo viral suppression following reintroduction of reverse transcriptase inhibitors.
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Mathis
authors.forename: Bettina
authors.initials: B
authors.lastname: Khanlari
authors.forename: Federico
authors.initials: F
authors.lastname: Pulido
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.forename: Eugenia
authors.initials: E
authors.lastname: Negredo
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Meynard
authors.forename: Jose
authors.initials: J
authors.lastname: Arribas
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
mesh_terms: D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D057194:Intention to Treat Analysis; D060046:Maintenance Chemotherapy; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors