A diffusion tensor imaging and neurocognitive study of ART-naïve and ART-treated children in Cape Town

Doctoral Thesis


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University of Cape Town

There are still no diagnostic criteria for a spectrum of neurocognitive disorders (ND) secondary to HIV infection for children. The American Academy of Neurology (AAN) proposes guidelines for assessment of HIV associated neurocognitive disorders (HAND) in HIV infected adults. A cross-sectional clinical cohort study was initiated in Cape Town, in which 120 participants, including a HIV negative healthy control group for comparison, completed clinical and neurocognitive assessments. HIV infected children were either stable on antiretroviral treatment (ART) for a minimum of 6 months or ART naïve. Neuroimaging was completed on 105 children in the cohort study. We compared 75 children vertically infected with HIV aged 6 to 16 years, including both children on antiretroviral therapy (ART) and ART-naïve, with 30 matched controls using diffusion tensor imaging (DTI) measures. We then used the detailed neurocognitive battery; an assessment of adaptive functioning and the AAN system for diagnosing ND to establish whether this system could detect a spectrum of ND in HIV infected older children and adolescents. When comparing HIV uninfected children to HIV infected children this DTI study found damaged neuronal microstructure in the HIV infected children. Significant associations were found between failing first line ART regimen, socio-demographic factors, nutritional-hematological status, HIV-relevant clinical variables, cognitive functioning and white matter integrity in children stable on ART. Children with a clinical diagnosis of encephalopathy (HIVE) had greater white matter damage when compared ART treated children without encephalopathy. DTI also found significant myelin loss in ART naïve children when compared with ART treated children. Using the AAN criteria for HAND, we found that 45.35% of the HIV infected children had a ND. ART naïve slow progressors, who receive limited attention from heath care service s, as they are thought to be 'well', were found to have neurocognitive impairment and white matter microstructural damage. HIV infected children were also more likely to have impaired competence in various domains of functioning. The current findings also underline the possible association of first line treatment failure with white matter brain dysfunction in children on ART. Despite the use of ART and improved virological control with immune reconstitution, there were still a significant percentage of children in this study who were found to have ND. Our findings also suggest that children on ART remain at risk for developing CNS disease, and that this risk extends to physically well ARV naïve slow progressors. The AAN HAND criteria designed for adults was able to identify children and adolescents with important functional cognitive impairments who don't fit criteria for HIVE and would therefore not have been identified otherwise.

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