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.

Background: Cognitive impairment is common in children and adolescents with human immunodeficiency virus (HIV). Brain magnetic resonance imaging (MRI) is a potentially useful tool to investigate the pathophysiology of HIV-associated cognitive impairment and may serve as a biomarker in future clinical trials. There are few published data on brain imaging in children with HIV in sub-Saharan Africa. Methods: Thirty-four perinatally infected subjects with HIV and age-matched HIV-exposed uninfected controls between the ages nine and 17 years were recruited from the Pediatric Center of Excellence in Lusaka, Zambia, as part of the HIV-associated Neurocognitive Disorders in Zambia study. Brain MRI sequences were acquired, and clinical and volumetric assessments were performed. Subjects underwent a comprehensive neuropsychologic battery, and cognitive impairment status was classified using a global deficit score approach. Regression models were used to evaluate relationships between MRI findings and cognitive function. Results: We identified cerebrovascular disease in seven of 34 subjects with HIV compared with zero of 17 controls (21% vs 0%, P ¼ 0.04). We also identified decreased total brain volumes (1036 vs 1162 cm 3 , P ¼ 0.03) and decreased cortical thickness in the right temporal lobes (3.12 vs 3.29 mm; P ¼ 0.01) and right fusiform gyri (3.10 vs 3.25 mm; P ¼ 0.02) of HIV-infected subjects with cognitive impairment. Conclusions: These findings support the hypothesis that brain volumes may be useful biomarkers for cognitive outcomes in children with HIV. Further studies are necessary to investigate mechanisms of cerebrovascular disease and volume loss in children with HIV.

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Background: Neurocysticercosis (NCC) is the most common parasitic infection of the brain and a leading cause of epilepsy in resource-limited settings. While NCC and Human Immunodeficiency Virus (HIV) co-infections have commonly been reported, there is little data on how they interact. As part of an observational study of HIV and cognition in Lusaka, Zambia, we identified a cluster of subjects with NCC. We hypothesized that neighborhood of residence may be an important factor driving clustering of NCC.Methods: 34 subjects with HIV and 13 subjects without HIV (ages 8-17) were enrolled in a prospective cohort study. All subjects had Magnetic Resonance Imaging (MRI) of the brain performed and were evaluated for NCC. Standardized interviews were conducted to identify potential risk factors for NCC. Quantitative Geographic Information Systems (QGIS) was utilized to investigate the relationship between neighborhood of residence, HIV, and NCC.Results: Three of 34 subjects with HIV (8.82%) and one of 13 controls were found to have NCC. Geographic cluster analysis demonstrated that all subjects with NCC were clustered in two adjacent neighborhoods (Chawama and Kanyama) with lower rates of piped water (C-22.8%, K-26.7%) and flush toilets (C-14.0%, K-14.0%) than surrounding neighborhoods.

Background: Multiple previous studies have identified a detrimental effect of pediatric HIV on cognitive function. Socioeconomic status (SES) is one of the strongest predictors of cognitive performance and may affect the relationship between HIV and cognition.Methods: As part of the ongoing HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) study, a prospective cohort study, we recruited 208 participants with HIV and 208 HIV-exposed uninfected controls, all aged 8-17 years. A standardized questionnaire was administered to assess SES, and all participants had comprehensive neuropsychological testing. An NPZ8 score was derived as a summary measure of cognitive function. Logistic regression and linear regression were used to model the relationship between SES and cognitive function, and mediation analysis was used to identify specific pathways by which SES may affect cognition. Results:Children with HIV performed significantly worse on a composite measure of cognitive function (NPZ8 score 20.19 vs. 0.22, P , 0.001) and were more likely to have cognitive impairment (33% vs. 19%, P = 0.001). Higher SES was associated with reduced risk of cognitive impairment (odds ratio 0.8, 95% confidence interval: 0.75-0.92, P , 0.001) in both groups, with similar effects in children with HIV and HIV-exposed uninfected groups. SES was more strongly correlated with NPZ8 score in children with HIV than in uninfected controls (Pearson's R 0.39 vs. 0.28), but predicted NPZ8 in both groups. Mediation analysis suggested that the effect of SES on cognition was most strongly mediated through malnutrition. Conclusions:Cognitive function is strongly correlated with SES in children with HIV, suggesting a synergistic effect of HIV and poverty on cognitive function.