title: Reduced darunavir dose is as effective in maintaining HIV suppression as the standard dose in virologically suppressed HIV-infected patients: a randomized clinical trial.
abstract: OBJECTIVE
  Maximizing ART efficiency is of growing interest. This study assessed the efficacy, safety, pharmacokinetics and economics of a darunavir dose-reduction strategy.
  
  
  METHODS
  This was a multicentre, randomized, open-label clinical trial in HIV-infected patients with plasma HIV-1 RNA <50 copies/mL while receiving triple ART including 800 mg of darunavir once daily. Participants were randomized to continue 800 mg of darunavir (DRV800) or to 600 mg of darunavir (DRV600), both once daily. Treatment failure was defined as two consecutive HIV-1 RNA determinations >50 copies/mL or discontinuation of study treatment by week 48. The study was registered at https://www.clinicaltrialsregister.eu (trial number 2011-006272-39).
  
  
  RESULTS
  Fifty participants were allocated to each arm. The mean (SD) CD4+ T cell count at baseline was 562 (303) cells/mm(3) and HIV-1 RNA had been <50 copies/mL for a median (IQR) of 106.9 (43.4-227.9) weeks before enrolment. At week 48 no treatment failure had occurred in 45/50 (90%) DRV600 patients and in 47/50 (94%) DRV800 patients (difference -4%; 95% CI lower limit, -12.9%). When only patients with virological data were considered, that endpoint was met by 45/48 (94%) in the DRV600 arm and 47/49 (96%) in the DRV800 arm (difference -2.2%; 95% CI lower limit, -9.6%). Darunavir exposure was similar in the two arms. The average reduction in annual cost per successfully treated DRV600-arm patient was US$7273.
  
  
  CONCLUSIONS
  The efficacy of a darunavir daily dose of 600 mg seemed to be similar to the efficacy of the standard 800 mg dose in virologically suppressed HIV-infected patients on triple ART. This strategy can potentially translate to substantial savings in the cost of care of HIV-infected patients.
authors.affiliation: Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Universitat Autònoma de Barcelona (UAB), Barcelona, Spain jmolto@flsida.org.
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.affiliation: Universitat Autònoma de Barcelona (UAB), Barcelona, Spain PKPD Modelling and Simulation, Institut de Recerca HSCSP-IIB St Pau, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Valle
authors.affiliation: Unitat VIH, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Ferrer
authors.affiliation: Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.affiliation: Universitat Autònoma de Barcelona (UAB), Barcelona, Spain Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Adrian
authors.initials: A
authors.lastname: Curran
authors.affiliation: Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Santos
authors.affiliation: Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: María Gracia
authors.initials: MG
authors.lastname: Mateo
authors.affiliation: Unitat VIH, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet, Barcelona, Spain.
authors.forename: María Silvana
authors.initials: MS
authors.lastname: Di Yacovo
authors.affiliation: Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Miranda
authors.affiliation: Unitat VIH, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.affiliation: Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Universitat Autònoma de Barcelona (UAB), Barcelona, Spain Fundació IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Universitat de Vic-Universitat Central de Catalunya (UVIC-UCC), Vic, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics; D000069454:Darunavir; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D060046:Maintenance Chemotherapy / Q000009:adverse effects / Q000191:economics / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D013449:Sulfonamides; D000069454:Darunavir
keywords: ART; HIV infection; dose optimization