limited numbers of participants in some of the subgroups. Discontinuation rates in ECHO and THRIVE were generally lower than in other studies and discontinuation rates were very similar for men and women in the RPV group, in contrast to other studies. As observed in past trials, nausea occurred more often in women while diarrhoea occurred more commonly in men. Unexpectedly, abnormal dreams WZ4002 and nightmares were more common among men than women in both the RPV and EFV groups. Consistent with previous trials, Black participants had lower response rates with higher rates of virological failure as well as discontinuations. Further research is needed to understand the etiology of the observed, generally small differences in response rates and safety findings with respect to gender and race.
Acknowledgements The authors are very grateful to the patients and their families for their participation and support during the study, the ECHO and THRIVE study teams from Johnson E7080 VEGFR inhibitor & Johnson and Tibotec, the study centre staff and principal investigators and the members of the Tibotec TMC278 team, in particular Guy De La Rosa, Eric Lefebvre, David Anderson, Bryan Baugh, Steven Nijs, Peter Williams and Eric Wong, for their input. Funding: This study was sponsored by Tibotec Pharmaceuticals. Editorial support was provided by Ian Woolveridge of Gardiner Caldwell Communications, Macclesfield, UK, this support was funded by Tibotec.
Conflicts of interest: SH has been a consultant for Bristol Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Merck Sharp & Dohme and Tibotec Therapeutics, and has received research grants from BMS, Gilead Sciences, GlaxoSmithKline, Pfizer and Tibotec AMG-208 Therapeutics, and travel/accommodation expenses from BI, Gilead Sciences, MSD and Tibotec Therapeutics. KA has received lecture fees and grant support from BMS, Roche, GSK, BI, Tibotec, MSD, Pfizer, ViiV Healthcare, Abbott Virology & Co, KG and Essex Pharma. JDW has acted as consultant for Abbott Laboratories Canada and served on advisory boards for Abbott Laboratories, BMS, Gilead Sciences, Tibotec and ViiV Healthcare. JG has received a grant and served on a speaker bureau for Tibotec/Johnson and Johnson. JG declares no conflicts of interest. PK has been an investigator for MSD, has served on a speaker bureau for BI and acted as a consultant, and has been a speaker for Abbott Laboratories and Tibotec.
LM has received travel/ accommodation expenses from Pfizer. WRS has been a consultant for Gilead Sciences, MSD and Tibotec Therapeutics. He has been on speakers, bureau for Gilead Sciences, MSD, Tibotec and BMS. HC, SV and KB are full time employees of Tibotec. Dapivirine is a non nucleoside reverse transcriptase inhibitor originally developed as an oral therapeutic before being selected for microbicide evaluation owing to poor bioavailability.5,6 Dapivirine is specific for, and binds directly to, HIV 1 reverse transcriptase, thereby blocking reverse transcriptase activity and preventing HIV 1 replication. Multiple in vitro studies have shown that dapivirine is able to inhibit both cell free and cell associated HIV 1 infection.7,8 Dapivirine is also able to inhibit direct infection of mucosal tissue in human cervical explant cultures and to prevent spread of virus by migratory cells. Inhi