School-Age Children Living With HIV Face Neuropsychological Challenges

Investigators of a new, multisite study evaluating neuropsychological development in African school-age kids found that children with perinatally-acquired HIV had poorer results on neuropsychological tests despite early ART initiation and viral suppression.

Earlier initiation of antiretroviral therapy (ART) improves outcomes for newborns with HIV. However, few studies have assessed the neuropsychological outcomes associated with administration of early ART in perinatally infected children.

Investigators of a new, multisite study published in Clinical Infectious Diseases have longitudinally evaluated the neuropsychological development of African school-age kids, finding that children with perinatally-acquired HIV had poorer results on neuropsychological tests despite early ART initiation and viral suppression.

The study focused on children 5 to <11 years of age at 6 different research sites. Enrollment took place in South Africa, Malawi, Zimbabwe, and Uganda between October 2013 and December 2014, with assessments continuing through December 2016.

A total of 3 cohorts were established: HIV-positive children, HIV-exposed but uninfected, and HIV-unexposed and uninfected. The research team also collected medical history and socioeconomic status information from study subjects.

Of 611 children tested, 246 were living with HIV and were initiated on ART before 3 years of age. The exposed but uninfected group comprised 183 children, and the unexposed and uninfected children numbered 182.

Most of the children living with HIV who were included in the study were receiving appropriate care. At time of enrollment, 239 of the 246 children living with HIV had >25% CD4 counts and 171 of 246 were aviremic.

Investigators administered a variety of tests across the 6 sites. The Kaufman Assessment Battery for Children (KABC-II) is a comprehensive assessment of cognitive ability that has been used in previous pediatric HIV studies across Africa.

The Bruininks-Oseretsky Test (BOT-2) was used to evaluate motor proficiency. The test includes items concerning fine motor integration, fine motor precision, upper-limb coordination, running speed, strength, and manual dexterity.

The Tests of Variables of Attention (TOVA) is used to assess attention deficit disorders and was used here to measure inattention (via response time variability), impulsivity of response time, inattention through omission errors, and other correlates of attention deficit-hyperactivity disorder.

Parents and guardians were given the Behavior Rating Inventory of Executive Function (BRIEF), an 86-item survey concerning their observation of day-to-day behavioral challenges related to executive dysfunction.

Caregivers also completed the 25-item Hopkins Symptom Checklist (HSCL-25) to evaluate caregiver depression and anxiety symptoms. Investigators noted a previously established connection between scores on the Hopkins Symptom Checklist and caregiver understandings of child behavior as reflected on the BRIEF.

The cohort of children living with HIV performed significantly worse than both other groups on the cognitive and motor skills tests KABC-II, TOVA, and BOT-2. In addition, despite some gains over time, children living with HIV showed less improvement than the other cohorts. The groups did not, however, show significant difference on the caregiver behavior assessment, BRIEF.

On the KABC-II Nonverbal Index, the group of children living with HIV had a least squares (LS) adjusted mean score of 72.64 compared to 77.14 in the exposed but uninfected group and 77.87 in the unexposed and uninfected group.

On the KABC-II mental processing index, the group of children with HIV scored a LS mean of 73.70 compared with 77.31 for the exposed but uninfected group and 79.01 for the unexposed and uninfected group.

For the BOT-2, the LS mean was 47.47 for the children who were HIV positive, 50.69 for the group who were exposed but uninfected, and 50.96 for those who were both unexposed and uninfected.

As access to HIV treatment improves and more children with perinatally-acquired HIV survive, concerns about executive function in children living with the condition will continue to grow.

Surveillance of neuropsychological conditions and neurocognitive therapies for children living with HIV may need to be enhanced to meet growing need.

“This study provides conclusive evidence that HIV+ African children are at significant neuropsychological risk, even with early ART treatment initiation and careful medical support,” study authors wrote.

Although HIV-associated neurocognitive disorder (HAND) is its own diagnosable condition separate from the general neuropsychological challenges faced by people living with HIV, evidence of an ability to improve cognitive function through speed-of-processing training to the point that patients no longer met the requirements for HAND diagnosis might indicate promising treatments worth exploring.