title: Darunavir minimum plasma concentration and ritonavir-boosted darunavir monotherapy outcome in HIV-infected patients.
abstract: BACKGROUND
  This study aimed to evaluate whether low darunavir (DRV) minimum plasma concentration (Cmin) values contribute to virological outcomes during DRV/ritonavir monotherapy (mtDRV/rtv).
  
  
  METHODS
  This was a prospective observational single-arm 96-week efficacy study in virologically suppressed subjects on triple therapy switched to mtDRV/rtv (800/100 mg every 24 h). Previous virological failures (VF) on protease-inhibitor-based regimens were allowed if the historical resistance tests showed no major resistance mutation to DRV/rtv. VF was defined as two consecutive HIV RNA measurements of >200 copies/ml. Efficacy was analysed by per-protocol and by intention-to-treat analyses. Plasma DRV Cmin values were measured by LC-MS/MS.
  
  
  RESULTS
  A total of 150 subjects were included. At week 96, the efficacy rate on treatment was 83.6% (95% CI 77.2%, 90.0%) by per-protocol analysis and 67.6% (95% CI 60.0%, 75.2%) by intention-to-treat. In the whole cohort the median (IQR) DRV Cmin was significantly higher during the periods of undetectable than of detectable viraemia (1.82 µg/ml [1.47-2.46] versus 1.56 µg/ml [0.93-2.32]; P=0.006) as well as in the subjects with blips and VF. However, a cutoff point sufficiently sensitive and specific could not be found.
  
  
  CONCLUSIONS
  The DRV Cmin values are related to viral control during mtDRV/rtv, but therapeutic drug monitoring cannot be recommended routinely as a precise cutoff point is unknown. Adherence is a key success factor on this regimen.
authors.affiliation: Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocio, Sevilla, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Gutierrez-Valencia
authors.forename: Almudena
authors.initials: A
authors.lastname: Torres-Cornejo
authors.forename: Omar J
authors.initials: OJ
authors.lastname: BenMarzouk-Hidalgo
authors.forename: Rosa
authors.initials: R
authors.lastname: Ruiz-Valderas
authors.forename: Amparo
authors.initials: A
authors.lastname: Lluch
authors.forename: Pompeyo
authors.initials: P
authors.lastname: Viciana
authors.forename: Luis F
authors.initials: LF
authors.lastname: López-Cortés
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000069454:Darunavir; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019233:Retreatment; D012307:Risk Factors; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir