title: Twenty-four-week efficacy and safety of switching virologically suppressed HIV-1-infected patients from nevirapine immediate release 200 mg twice daily to nevirapine extended release 400 mg once daily (TRANxITION).
abstract: OBJECTIVE
  Once-daily (qd) antiretroviral therapies improve convenience and adherence. If found to be effective, nevirapine extended release (NVP XR) will confer this benefit. The TRANxITION trial examined the efficacy and safety of switching virologically suppressed patients from NVP immediate release (NVP IR) 200 mg twice daily to NVP XR 400 mg qd.
  
  
  METHODS
  An open-label, parallel-group, noninferiority, randomized (2:1 NVP XR:NVP IR) study was performed. Adult HIV-1-infected patients receiving NVP IR plus a fixed-dose nucleoside reverse transcriptase inhibitor (NRTI) combination of lamivudine (3TC)/abacavir (ABC), tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV) with undetectable viral load (VL) were enrolled in the study. The primary endpoint was continued virological suppression with VL < 50 HIV-1 RNA copies/mL up to week 24 (calculated using a time to loss of virological response algorithm). Cochran's statistic (background regimen adjusted) was used to test noninferiority. Adverse events (AEs) were recorded.
  
  
  RESULTS
  Among 443 randomized patients, continued virological suppression was observed in 93.6% (276 of 295) of NVP XR- and 92.6% (137 of 148) of NVP IR-treated patients, an observed difference of 1% [95% confidence interval (CI) -4.3, 6.0] at 24 weeks of follow-up. Noninferiority (adjusted margin of -10%) of NVP XR to NVP IR was robust and further supported by SNAPSHOT analysis. Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 3 and 4 events were similar for the NVP XR and NVP IR groups (3.7 vs. 4.1%, respectively), although overall AEs were higher in the NVP XR group (75.6 vs. 60.1% for the NVP-IR group).
  
  
  CONCLUSIONS
  NVP XR administered once daily resulted in continued virological suppression at week 24 that was noninferior to that provided by NVP IR, with similar rates of moderate and severe AEs. The higher frequency of overall AEs with NVP XR may be a consequence of the open-label design.
authors.affiliation: EPIMED c/o Vivantes Auguste-Viktoria Hospital, Berlin, Germany. keikawus.arasteh@vivantes.de
authors.forename: K
authors.initials: K
authors.lastname: Arasteh
authors.forename: D
authors.initials: D
authors.lastname: Ward
authors.forename: A
authors.initials: A
authors.lastname: Plettenberg
authors.forename: J M
authors.initials: JM
authors.lastname: Livrozet
authors.forename: C
authors.initials: C
authors.lastname: Orkin
authors.forename: C
authors.initials: C
authors.lastname: Cordes
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: C L
authors.initials: CL
authors.lastname: Yong
authors.forename: P
authors.initials: P
authors.lastname: Robinson
authors.forename: A
authors.initials: A
authors.lastname: Quinson
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D057915:Drug Substitution; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine