Longitudinal Cognitive Outcomes in Children With HIV in Zambia: 2-Year Outcomes From the HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) Study

Abstract

Background: Multiple studies have shown that children with HIV are at risk for impaired cognition. However, there are limited data on longitudinal cognitive outcomes in children with HIV. Methods:We conducted a prospective cohort study of 208 perinatally infected children with HIV ages 8-17 years, all treated with antiretroviral therapy, and 208 HIV-exposed uninfected controls. Participants were followed for 2 years. Cognition was assessed with a custom NIH Toolbox Cognition Battery, and tests were combined to generate a Summary Cognition Score (SCS). The contribution of potential risk factors to outcomes was explored using regression models and group-based trajectory modeling.Results: HIV was strongly associated with lower SCS at baseline [b-14, 95% confidence interval (CI): 220 to 27, P , 0.001]. Change scores over time were similar between groups, but poorer average performance in children with HIV persisted at the 2-year follow-up visit (adjusted b = 211, 95% CI: 222 to 20.3, P = 0.04). Other than HIV, the strongest predictors of baseline SCS included socioeconomic status index (b =3, 95% CI: 1, 5, P = 0.004), history of growth stunting (b=214, 95% CI: 223 to 26, P = 0.001), history of CD4 count below 200 (b = 219, 95% CI: 235 to 22, P = 0.02), and history of World Health Organization stage 4 disease (b = 210, 95% CI: 219 to 20.2, P = 0.04). In the group-based trajectory model, HIV+ status predicted membership in the lowest performing trajectory group (odds ratio 2.5, 95% CI: 1.2 to 5.1, P = 0.01). Conclusions:Children with HIV are at risk of poor cognitive outcomes, despite chronic treatment with antiretroviral therapy.

Early Initiation of Antiretroviral Therapy is Protective Against Seizures in Children With HIV in Zambia: A Prospective Case–Control Study

“…The most common etiologies of seizures in our population included CNS infection and HIV encephalopathy, and both of these etiologies may be reduced by early treatment with ART. 12,16,19 Our study also notes that nutritional status including being underweight and stunted are strongly associated with seizures. This complements recent findings from the HANDZ study that chronic malnutrition in children with HIV may be a key factor contributing to poor neurologic outcomes.…”

“…[1][2][3][4][5][6] HIV may lead to seizures through a variety of mechanisms, including immune suppression leading to opportunistic infections, metabolic disturbances, toxicity of antiretroviral drugs, and chronic inflammation in the central nervous system (CNS). [7][8][9][10][11][12][13][14][15][16] Treatment of seizures is particularly challenging in populations with HIV in sub-Saharan Africa, given difficulties accessing diagnostic tests and antiseizure drugs and potential drug interactions between antiretroviral therapy (ART) and anti-seizure medications. 17 The widespread introduction of ART has transformed the HIV pandemic in low-and middle-income countries, with severe immunosuppression becoming much less common.…”

“…Our primary hypothesis was that early initiation of combination ART and sustained viral suppression would be associated with a reduced risk of seizures. Based on the results from the HIV-associated Neurocognitive Disorders in Zambia (HANDZ) study suggesting that malnutrition is a major risk factor for poor neurologic outcomes, 16 we also hypothesized that indicators of malnutrition would be associated with new-onset seizures.…”