Background:
Children with HIV may experience adverse neuropsychological outcomes despite antiretroviral treatment (ART). Uncontrolled cytomegalovirus (CMV) is common in children with HIV. Among children on ART, we examined the influences of early CMV DNA, HIV DNA, and viral load (VL) on neurocognition.
Methods:
Children who initiated ART before 12 months of age were enrolled from 2007-2010 in Nairobi, Kenya. Blood was collected at enrollment and every 6 months thereafter. Neuropsychological assessments were conducted when children were a median age of 7 years. Primary outcomes included cognitive ability measured by the Kaufman Assessment Battery for Children 2nd Edition (KABC), executive function measured by Behavior Rating Inventory of Executive Functioning (BRIEF), motor measured by Bruinick’s-Oseretsky Test of Motor Proficiency 2nd Edition Brief Form (BOT), and attention measured by Visual Test of Variables of Attention (TOVA). Secondary outcomes included short-term memory, visual-spatial, learning, non-verbal, and delayed memory from the KABC; behavior regulation and metacognition from the BRIEF; and processing speed from the TOVA. Generalized linear models were used to determine associations between HIV VL (pre-ART and cumulative), peak total and intact HIV DNA (by 12 months of age), peak CMV DNA (by 24 months of age) and neuropsychological outcomes.
Results:
Overall, 39 children completed neuropsychological assessments. Median age at ART initiation was 4.6 months. In adjusted models, higher peak CMV viremia by 24 months of age was associated with lower cognitive ability and motor z-scores. Higher pre-ART HIV VL, total HIV DNA, and intact HIV DNA were associated with lower executive function z-scores. Higher HIV DNA levels also were associated with higher motor z-scores and higher intact HIV DNA with higher attention z-scores. Among secondary outcomes, higher intact HIV DNA levels were associated with lower behavior regulation z-scores and higher pre-ART VL was associated with lower nonverbal and metacognition z-scores.
Conclusions:
Pre-ART VL, early post-ART total and intact HIV DNA, and CMV DNA in infancy predicted neuropsychological scores in childhood. These findings suggest long-term benefits of early HIV viral suppression, reservoir containment, and CMV control on neurocognition.