title: Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues.
abstract: BACKGROUND
  In previous studies in virologically suppressed patients, protease inhibitor monotherapy has shown trends for more low-level elevations in HIV-1 RNA compared with triple therapy, but no increase in the risk of drug resistance.
  
  
  METHODS
  A total of 273 patients with HIV-1 RNA less than 50 copies/ml on first-line antiretrovirals switched to darunavir/ritonavir (DRV/r) 800/100 mg once daily, either as monotherapy (n = 137) or as triple therapy with two nucleoside analogues (n = 136). Treatment failure was defined as HIV-1 RNA levels 50 copies/ml or above, or discontinuation of study treatment by week 48 (FDA Snapshot algorithm).
  
  
  RESULTS
  Patients were 83% male and 88% white, with mean age 42 years. In the primary efficacy analysis, HIV-1 RNA less than 50 copies/ml by week 48 [intention-to-treat (ITT)] was 118 of 137 (86%) in the DRV/r monotherapy arm versus 129 of 136 (95%) in the triple therapy arm (difference = -8.7%, 95% confidence interval -15.50, -1.80). In a post-hoc analysis, for patients with nadir CD4 cell count 200 cells/μl or above, rates of HIV-1 RNA suppression were 91 of 96 (95%) in the DRV/r monotherapy arm and 100 of 106 (94%) in the triple therapy arm. There was no difference in neurocognitive function or the risk of neuropsychiatric adverse events between DRV/r monotherapy and triple therapy. Two patients in the monotherapy arm with CD4 nadir less than 200 cells/μl developed viraemia in both cerebrospinal fluid (CSF) and plasma, with one symptomatic case.
  
  
  CONCLUSIONS
  In this study for patients with HIV-1 RNA less than 50 copies/ml at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple therapy at week 48 in the primary ITT switch equals failure analysis, with two cases of viraemia in the CSF in the protease inhibitor monotherapy arm.
authors.affiliation: aNational Institute for Infectious Diseases, L. Spallanzani IRCCS, Rome, Italy bBrighton and Sussex University Hospitals, Brighton, UK cKarolinska University, Sjukhuset, Sweden dHospital Universitario La Paz, IdiPAZ, Madrid, Spain eMedical Research Council, HIV Clinical Trials Unit, London, UK fDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zürich, Zürich, Switzerland gCopenhagen University Hospital, Copenhagen, Denmark hWarsaw Medical University, Infectious Diseases, Warsaw, Poland iUniversity Hospital Germans Trias I Pujol, irsiCaixa, Badalona, Spain jInfectious Diseases, Ospedale Papa Giovanni XXIII, Bergamo, Italy kDepartment of Infectious and Tropical Diseases, Hôpital Saint-Antoine, AP-HP, and INSERM UMR S 1136, Paris, France lUniversity of Liverpool, Liverpool, UK mJanssen, EMEA, Neuss, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Amanda
authors.initials: A
authors.lastname: Clarke
authors.forename: Veronika
authors.initials: V
authors.lastname: Svedhem-Johansson
authors.forename: José R
authors.initials: JR
authors.lastname: Arribas
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arenas-Pinto
authors.forename: Jan
authors.initials: J
authors.lastname: Fehr
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Andrzej
authors.initials: A
authors.lastname: Horban
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Diego
authors.initials: D
authors.lastname: Ripamonti
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hill
authors.forename: Christiane
authors.initials: C
authors.lastname: Moecklinghoff
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D001927:Brain Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D002490:Central Nervous System / Q000473:pathology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents