Neurodevelopmental Outcome among HIV+ Children >1 Year of Age Randomized to Immediate vs Deferred ART: The PREDICT Study (NCT00234091)
T Puthanakit1,2, Jintanat Ananworanich*1,2,3, S Vonthanak4, P Kosalaraksa5, R Hansudewechakul6, S Kerr1,7, S Kanjanavanit8, U Vibol9, R Paul10, K Ruxrungtham1,2, and PREDICT Study Group
1HIVNAT Res Collaboration, Thai Red Cross AIDS Res Ctr, Bangkok; 2Chulalongkorn Univ Faculty of Med, Bangkok, Thailand; 3South East Asia Res Collaboration with Hawaii and Thai Red Cross AIDS Res Ctr, Bangkok; 4Natl Ctr for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia; 5Khon Kaen Univ Faculty of Med, Thailand; 6Chiangrai Prachanukroh Hosp, Chiang Rai, Thailand; 7Kirby Inst for Infection and Immunity in Society, Sydney, Australia; 8Nakornping Hosp, Chiang Mai, Thailand; 9Natl Pediatric Hosp, Phnom Penh, Cambodia; and 10Univ of Missouri, St Louis, US
Background: It is uncertain whether nadir CD4 percentage affects neurodevelopmental outcomes. The PREDICT neuro-substudy compared neurodevelopmental outcomes at 144 weeks after HIV+ Cambodian and Thai children were randomized to immediate vs deferred ART.
Methods: HIV+ children aged 1 to 12 years with CD4 15% to 24% and no AIDS-defining illness who were randomized to initiate ART at enrollment (immediate) or when CD4 <15% or CDC C events developed (deferred) underwent neuropsychological testing including the Beery Visual Motor Integration (VMI, age >2 years), Purdue Pegboard (age >5 years), Color Trails (age >8 years), and child behavioral checklist. Thai children also completed the Wechsler Intelligence Scale, WPPSI-III/WISC-III. Data are presented as mean (SD) standard scores based on Western norms except for Purdue Pegboard, which are mean (SD) number of successful pin placements. Statistical comparisons used regression models based on standard scores except for Color Trails and Purdue Pegboard where age- and gender-adjusted raw and count scores, respectively, were used. Age-matched HIV– Thai and Cambodian children were enrolled for comparison.
Results: We enrolled 284 HIV+ children and 164 HIV– children at median age 7 (IQR 5 to 9) years; 58% were female, and 62% were Thai. Median CD4 nadirs were 18% (IQR 15 to 21) in the immediate and 15% (13 to 17) in the deferred arms, p <0.001. At week 144, only 69 (48%) children in the deferred arm had started ART (median ART duration 81 (IQR 54 to 106) weeks). Median CD4 were 33% (IQR 29 to 37) and 24% (IQR 19 to 30) in the immediate and deferred arms, respectively. There were no significant differences between the immediate and deferred arms for any of the ND scores (see the table). However, both HIV+ groups scored significantly lower on IQ and Berry VMI, but not on Purdue Pegboard and Color Trails, compared to HIV– controls.
Conclusions: Despite lower nadir CD4 percentage and less time on ART for children randomized to deferred initiation of ART, no significant differences in neurodevelopmental outcomes at week 144 were observed when compared to children randomized to immediately initiated ART. However, intelligence and Beery scores were significantly lower than the age- and ethnic-matched HIV– controls, suggesting that despite effective ART, children infected with HIV experience global cognitive challenges relative to uninfected peers