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 matching 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 unblinded following the results of adult trials showing a benefit of combination antiretroviral therapy (ART) over monotherapy, but follow up continued and is reported here until December 1998 (total follow up 4.6 years). Median time to starting ART in the deferred group was 2.7 years; 19% of deferred children had not started ART by 1999. Throughout follow up, the percentage 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 deferred groups. During the blinded phase eight (7.8%) immediate and 12 (13.3%) deferred children developed AIDS or died (log rank p = 0.24); overall 21 immediate and 20 deferred children progressed. In an analysis including all children regardless of original allocation, the risk of progression to AIDS or death, adjusting for age and time since trial entry was significantly lower during 1997-98 (2.4 per 100 child years) than during 1992-96 (6.6 per 100 child years), most likely a result of increased use of combination ART

HIV-1 viral load and CD4 cell count in untreated children with vertically acquired asymptomatic or mild disease. Paediatric European Network for Treatment of AIDS (PENTA).

BACKGROUND: Plasma HIV-1 RNA levels are high in vertically infected infants. Information in older children is limited, particularly in those who have not received antiretroviral therapy. OBJECTIVES: To describe the relationships between HIV-1 RNA, age and CD4 cell count in untreated vertically infected children. DESIGN: HIV-1 RNA was measured in 70 children [median age, 3.5 years (range, 0.4-11.9 years); median CD4 cell count, 881 x 10(6)/l (interquartile range, 576-1347 x 10(6) cells/l)] enrolled in a randomized placebo-controlled trial comparing immediate with deferred zidovudine in asymptomatic or mildly symptomatic vertically infected children (PENTA-1 trial). Short-term variability was assessed by comparing HIV-1 RNA at -2 and 0 weeks (prior to randomization). The relationship between age and HIV-1 RNA, and CD4 cell count was analysed using data from all children prior to randomization and sequential samples from 35 remaining on placebo for up to 105 weeks, by fitting mixed linear models. RESULTS: The within-individual SD in viral load was 0.26 log10 copies/ml. The median plasma HIV-1 RNA at enrollment was 4.61 log10 (range, 2.3-6.56 log10 copies/ml), significantly higher in children aged 2 years (4.51 log10 copies/ml; P < 0.0001). Mean HIV-1 RNA fell by 0.38 log10 copies/ml per year up to 2 years of age, by 0.21 log10 copies/ml per year from 2 to 4 years of age, and by 0.03 log10 copies/ml per year from 4 to 6 years of age reaching a nadir of 4.25 log10 copies/ml at 6 years. Mean log10 CD4 cell count declined steadily with age and was not significantly correlated with HIV-1 RNA, although there was some evidence that the rate of log10 CD4 cell decline was negatively correlated with the initial rate of HIV-1 RNA decline. No mutations associated with resistance to zidovudine were observed. CONCLUSIONS: Age is a key factor in the interpretation of both viral load and CD4 cell count in vertically infected childre