h a lower incidence of rash, dizziness, abnormal dreams/ nightmares and treatment E7080 related grade 2 4 adverse events, as well as smaller increases in lipids compared with EFV. Longer term follow up over 192 weeks in a phase IIb trial in treatment naïve adult patients showed RPV 25 mg qd had similar efficacy, a lower incidence of grade 2 4 AEs and smaller lipid increases compared with EFV 600 mg qd. RPV has not shown any teratogenic potential in preclinical studies. The aim of the current analysis was to evaluate the influence of gender and race on efficacy, tolerability and safety in the ECHO and THRIVE trials at week 48. Methods Study design ECHO and THRIVE were international, phase III, doubleblind, double dummy, randomized trials conducted among treatment naïve, HIV 1 infected adults.
The primary objective of both trials was to determine PLX-4720 Raf inhibitor whether treatment with RPV was noninferior to EFV in terms of confirmed response at week 48. The main inclusion criteria were baseline viral load 5000 copies/mL, treatment naïve with absence of NNRTI resistance associated mutations and sensitivity to the NRTIs in the background regimen as determined by vircoTYPE HIV 1. Patients were randomized to receive RPV 25 mg qd or EFV 600 mg qd, plus a combination of two NRTIs: TDF and FTC in the ECHO trial and investigator selected TDF/ FTC, zidovudine /lamivudine or abacavir /3TC in the THRIVE trial. Written informed consent was obtained from all participants. Study protocols were reviewed and approved by the appropriate institutional ethics committees and health authorities, and the trials were conducted in accordance with the Declaration of Helsinki.
AEs were assessed using the AIDS Clinical Trials Group Division of AIDS table for grading the severity BMS-708163 of adult and paediatric AEs. Reported AEs were classified using the Medical Dictionary for Regulatory Activities. Safety and efficacy assessments were conducted at screening, at baseline, at weeks 2 and 4, every 4 weeks until week 16, and every 8 weeks until week 48. Adherence was assessed using the Modified Medication Adherence Self Report Inventory. The ITT population was used for all analyses. Efficacy and safety data were assessed according to self reported gender and race. The ECHO and THRIVE trials were not specifically designed to examine differences between such subgroups, although the pooling of results from the two trials provides a more robust data set with which to conduct these analyses.
We also assessed whether there were differences in response rates between Hispanic/Latino patients and other ethnic groups, or between Black patients participating in trial centres in African countries compared with Black patients living in other continents. The primary efficacy analysis was conducted at the week 48 time point. The Breslow Day test was used to assess differences between subgroups in response rates and virological failure rates. The safety analysis included all available data, including those collected beyond week 48. The incidence of AEs and of laboratory abnormalities was evaluated. The potential relationship between selected continuous and categorical factors, including gender or race, and RPV pharmacokinetics, as determined with the population pharmacokinetic model, was evaluated in a covariate anal