The HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) Study: Protocol of a research program in pediatric HIV in sub-Saharan Africa

Abstract

Approximately 10% of youth in sub-Saharan Africa are infected with the Human Immunodeficiency Virus. In Zambia, it is estimated that over 72,000 children have HIV infection, and despite access to combination antiretroviral therapy, many will experience HIV-associated neurocognitive deficits (HAND) encompassing cognitive and psychiatric sequelae such as global intellectual delay, executive dysfunction, and depressed mood. However, little is known about the neurocognitive profile of such children, the long-term outcomes and impacts of HAND, or the predictors and risk factors for HAND-related impairment. We have initiated the first-ever prospective, longitudinal study of neurocognition in children with HIV-infection in Zambia. Our overarching study goals are to validate cognitive and psychiatric testing tools in children with HIV infection in Zambia, and to determine if inflammatory biomarkers and brain imaging can prospectively identify children at high risk of developing HAND. This article outlines the study methods, highlights several challenges encountered in the initiation of the study, and offers solutions to these challenges.

Brain Magnetic Resonance Imaging Findings Associated With Cognitive Impairment in Children and Adolescents With Human Immunodeficiency Virus in Zambia

“…Detailed methods for the parent HANDZ study have previously been described. 18 HIV-infected subjects aged eight to 17 years were recruited from the Pediatric Center of Excellence in Lusaka, Zambia, from October 2017 to January 2019 from outpatient medication refill visits. For the imaging substudy of HANDZ, the first 34 eligible subjects with HIV from HANDZ had brain MRI performed.…”

“…HIV-related clinical information and past medical history were determined through chart review, and through subject and parental interviews. 18…”

“…Neuropsychological testing in HANDZ has previously been described in detail. 18 Briefly, neuropsychologic testing was performed using both standard techniques and computerized testing using the NIH Toolbox for Assessment of Neurological and Behavioral Function. 19 All tests have been previously validated in this population in Zambia.…”

“…19 All tests have been previously validated in this population in Zambia. 18 Eight cognitive domains commonly affected by HIV infection were assessed: executive function/ response inhibition, set shifting, attention, processing speed, immediate recall, verbal fluency, nonverbal reasoning, and motor speed. Raw test scores were transformed for normality and converted into age-and sex-adjusted z scores for each domain.…”

“…Further details of HIV-specific characteristics of this population have previously been described. 18,32 Clinical magnetic resonance imaging results Subjects with HIV were slightly more likely to have abnormalities noted on clinical MRI reads (50% vs 35%; P ¼ 0.5; see Table 2). Clinical pathology noted on MRI scans was similar between cases and controls, with the exception of cerebrovascular disease, which was seen in seven of 34 subjects with HIV and in no controls (21% vs 0%; P ¼ 0.04).…”