Neurodevelopmental delay in pediatric HIV/AIDS: current perspectives

Abstract

The effects of HIV on the developing nervous system of perinatally HIV (PHIV)- infected children are substantial, yet poorly understood. While the introduction of combination antiretroviral therapy (cART) reduced the prevalence of HIV encephalopathy, many cART- treated PHIV-infected children still present with neurodevelopmental delays and cognitive impairment. The underlying pathogenesis may partially differ from that in adults, as HIV not only causes direct injury to the central nervous system (CNS) but may also impede the development of the pediatric brain. Increasing evidence implies significant roles for ongo - ing neuroinflammation, vascular dysfunction and hypercoagulability induced by HIV despite adequate viral suppression. Subsequent manifestations of HIV in the pediatric brain include gray-matter volume reduction, white-matter lesions, and basal ganglia calcifications, but even in the absence of such macrostructural changes, the detrimental effects of HIV are clearly revealed in widespread microstructural changes, such as poorer white-matter integrity and alterations in cerebral metabolites and blood flow. Viral suppression on cART evidently does not fully protect against cerebral injury, but knowledge concerning the pharmacokinetics and toxicity of cART in the pediatric CNS is lacking. Investigations combining neuropsychological assessment, multimodal neuroimaging, and laboratory evaluation of inflammatory and neurodegenerative markers could greatly increase our understanding of the pathogenesis of HIV in the developing nervous system and improve treatment and prevention strategies. Longitudinal research will be crucial to observe the long-term consequences of CNS exposure to HIV and cART in PHIV- infected children as they survive into adulthood.