title: The Intelence aNd pRezista Once A Day Study (INROADS): a multicentre, single-arm, open-label study of etravirine and darunavir/ritonavir as dual therapy in HIV-1-infected early treatment-experienced subjects.
abstract: OBJECTIVE
  Following antiretroviral therapy failure, patients are often treated with a three-drug regimen that includes two nucleoside/tide reverse transcriptase inhibitors [N(t)RTIs]. An alternative two-drug nucleoside-sparing regimen may decrease the pill burden and drug toxicities associated with the use of N(t)RTIs. The Intelence aNd pRezista Once A Day Study (INROADS; NCT01199939) evaluated the nucleoside-sparing regimen of etravirine 400 mg with darunavir/ritonavir 800/100 mg once-daily in HIV-1-infected treatment-experienced subjects or treatment-naïve subjects with transmitted resistance.
  
  
  METHODS
  In this exploratory phase 2b, single-arm, open-label, multicentre, 48-week study, the primary endpoint was the proportion of subjects who achieved HIV-1 RNA < 50 copies/mL at week 48 [confirmed virological response (CVR), non-virological failure (VF) censored]. Key secondary endpoints included assessments of changes from baseline to week 48 in viral load, immunological response, pharmacokinetics/pharmacodynamics, safety, tolerability, metabolic and bone markers and body fat.
  
  
  RESULTS
  Forty-one of the 54 enrolled subjects completed the study. Adverse events (7%) and VF (7%) were the most common reasons for discontinuation. The week 48 CVR rate in the intent-to-treat (ITT) non-VF censored population was 89% (primary endpoint). Seven subjects experienced VF. Common adverse events were diarrhoea (15%), rash (15%) and upper respiratory tract infection (11%). Mild/moderate lipid elevations, minimal changes in limb fat distribution and bone mineral density and no clinically relevant changes in glucose metabolism were observed.
  
  
  CONCLUSIONS
  Etravirine 400 mg and darunavir/ritonavir 800/100 mg as a two-drug once-daily regimen in treatment-experienced subjects or treatment-naïve subjects with transmitted resistance was virologically efficacious and well tolerated.
authors.affiliation: Peter J. Ruane MD Inc., Los Angeles, CA, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Ruane
authors.forename: C
authors.initials: C
authors.lastname: Brinson
authors.forename: M
authors.initials: M
authors.lastname: Ramgopal
authors.forename: R
authors.initials: R
authors.lastname: Ryan
authors.forename: B
authors.initials: B
authors.lastname: Coate
authors.forename: M
authors.initials: M
authors.lastname: Cho
authors.forename: T N
authors.initials: TN
authors.lastname: Kakuda
authors.forename: D
authors.initials: D
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D050218:Body Fat Distribution; D015519:Bone Density / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011743:Pyrimidines; D012367:RNA, Viral / Q000187:drug effects; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D008055:Lipids; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; D013449:Sulfonamides; C451734:etravirine; D019438:Ritonavir; D000069454:Darunavir
keywords: HIV-1; darunavir; etravirine; nucleoside-sparing; race; treatment-experienced