The prevalence of cognitive impairment or learning difficulties in HIV-infected children is high despite access to antiretroviral treatment (ART). Several biological mechanisms, including latent HIV reservoir persistence in the brain, local inflammation within the central nervous system (CNS), disruption of neuronal function and integrity, and ongoing infiltration of activated HIV target cells to the CNS during brain development, may each dampen efficacy of ART. Development of therapeutics to target these mechanisms will be crucial, and potential candidates may include chemokine receptor antagonists. Separately, psychosocial approaches to support caregiving may leverage neuroplasticity and support brain development during critical developmental windows in spite of perinatal HIV infection. Multipronged approaches that encompass both approaches are crucial for optimizing neurodevelopmental outcomes in these extraordinarily vulnerable children. Dynamic neuropsychological assessments, such as what can be obtained with the use of computerized cognitive games intervention, may prove more sensitive to the brain/behavior benefits of ART. Dynamic neuropsychological outcomes, neuroinflammatory biomarkers, and brain development neuroprotective factors (BDNFs) may each be used to evaluate brain/behavior integrity of children in response to new treatment options.
Keywords: Antiretroviral; Caregiving; Cognitive rehabilitation; Monocyte; Neurocognitive; Neurodevelopment; Perinatal HIV.
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