African Multi-Site 2-Year Neuropsychological Study of School-Age Children Perinatally Infected, Exposed, and Unexposed to Human Immunodeficiency Virus

Abstract

Background Children living with human immunodeficiency virus (HIV) are at neuropsychological risk for cognitive and motor dysfunction. However, few prospective, multi-site studies have evaluated neuropsychological outcomes longitudinally among perinatally infected African children who received early antiretroviral treatment (ART). Methods We enrolled 611 children aged 5 to 11 years at 6 sites (South Africa [3], Zimbabwe, Malawi, Uganda). Of these, there were 246 children living with HIV (HIV+) who were initiated on ART before 3 years of age in a prior clinical trial comparing nevirapine to lopinavir/ritonavir (International Maternal Pediatric Adolescent Acquired Immunodeficiency Syndrome Clinical Trials [IMPAACT] P1060); 183 age-matched, exposed but uninfected (HEU) children; and 182 unexposed and uninfected (HUU) children. They were compared across 3 assessment time points (Weeks 0, 48, and 96) on cognitive ability (Kaufman Assessment Battery for Children, second edition [KABC-II]), attention/impulsivity (Tests of Variables of Attention [TOVA]), motor proficiency (Bruininks-Oseretsky Test, second edition [BOT-2]), and on the Behavior Rating Inventory of Executive Function (BRIEF). The cohorts were compared using linear mixed models, adjusting for site, child’s age and sex, and selected personal/family control variables. Results The HIV+ cohort performed significantly worse than the HEU and HUU cohorts for all KABC-II, TOVA, and BOT-2 performance outcomes across all 3 time points (P values < .001). The HUU and HEU cohorts were comparable. For the KABC-II planning/reasoning subtests, the HIV+ children showed less improvement over time than the HUU and HEU groups. The groups did not differ significantly on the BRIEF. Conclusions Despite initiation of ART in early childhood and good viral suppression at the time of enrollment, the HIV+ group had poorer neuropsychological performance over time, with the gap progressively worsening in planning/reasoning. This can be debilitating for self-management in adolescence.

Reduced neuronal population in the dorsolateral prefrontal cortex in infant macaques infected with simian immunodeficiency virus (SIV)

“…Perinatally HIV-infected (pHIV) children consistently present with a higher prevalence of neurological impairment than infected adults despite controlled viremia with ART ( Cohen et al 2015 ; Phillips et al 2016 ). Neuropsychological evaluations suggest that pHIV children display deficits in planning/reasoning, cognitive ability, motor proficiency, working memory, attention/impulsivity, IQ, and executive function ( Boivin et al 2019 ; Cohen et al 2015 ; Nichols et al 2016 ; Phillips et al 2016 ; Van den Hof et al 2019b ). The neurodevelopmental sequelae of pHIV children have long-term consequences.…”

Neurodevelopment in early treated HIV‐infected infants participating in a developmental stimulation programme compared with controls

“…Furthermore, child development is influenced by a myriad of socio‐environmental factors affecting children raised in families affected by HIV, which may become more evident as the child ages. An African multisite study of HEI school‐age children on suppressive ART initiated in early childhood concluded the children as being at significant neuropsychological risk, even with ART and medical support (Boivin et al, 2019).…”

“…ages. An African multisite study of HEI school-age children on suppressive ART initiated in early childhood concluded the children as being at significant neuropsychological risk, even with ART and medical support (Boivin et al, 2019).…”

The Relationship Between Central Auditory Tests and Neurocognitive Domains in Adults Living With HIV

“…The Test of Variables of Attention (TOVA. Version 8.0) was also administered to all subjects as it has been used with sub-Saharan African populations across a wide range of 1 www.Cogstate.com studies (Bangirana et al, 2015;Boivin et al, 2019). The TOVA has several advantages because it uses visual stimuli, measures response times precisely (±1 m sec), is language-and culturefree, and has a history of use in resource-challenged areas (Ruel et al, 2012).…”