Five year follow up of vertically HIV infected children in a randomised double blind controlled trial of immediate versus deferred zidovudine: the PENTA 1 trial

A total of 195 children were randomised to zidovudine (immediate) or matchi ng placebo (deferred) in a multicentre double blind trial in vertically HIV infected children with early disease (the PENTA 1 trial). Median follow up in the blinded phase was 1.9 years. Thereafter, individual children were u nblinded following the results of adult trials showing a benefit of combina tion antiretroviral therapy (ART) over monotherapy, but follow up continued and is reported here until December 1998 (total follow up 4.6 years). Medi an time to starting ART in the deferred group was 2.7 years; 19% of deferre d children had not started ART by 1999. Throughout follow up, the percentag e of time spent on no ART, monotherapy, dual, and triple ART was 21%, 44%, 29%, and 6% respectively for immediate and 62%, 12%, 18%, and 8% for deferr ed groups. During the blinded phase eight (7.8%) immediate and 12 (13.3%) d eferred children developed AIDS or died (log rank p = 0.24); overall 21 imm ediate and 20 deferred children progressed. In an analysis including all ch ildren regardless of original allocation, the risk of progression to AIDS o r death, adjusting for age and time since trial entry was significantly low er during 1997-98 (2.4 per 100 child years) than during 1992-96 (6.6 per 10 0 child years), most likely a result of increased use of combination ART.