Review article
Neurologic and neurodevelopmental manifestations of pediatric HIV/AIDS: A global perspective

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Abstract

Neurodevelopmental abnormalities associated with HIV infection have been described since the first reports of pediatric AIDS in the 1980s. Before antiretroviral therapy (ART) became widely available, progressive HIV-1 encephalopathy (PHE) was reported in the US in 13–35% of children with HIV-1 infection and in 35–50% of children with AIDS. Introduction of ART can prevent PHE and reverse PHE present at ART initiation, but a high prevalence of residual problems has been described. Even though 90% of HIV-infected children live in the developing world, few children have access to ART and little is known regarding the neurological manifestations of perinatal HIV infection in those regions.

Mechanisms of pediatric HIV-1 neuropathogenesis and factors associated with neurodevelopmental abnormalities in perinatally infected children are not yet fully understood. Studies have demonstrated that HIV-1 enters the CNS soon after infection and may persist in this compartment over the entire course of HIV-1 infection. The CNS is a distinct viral reservoir, differing from peripheral compartments in target cells and antiretroviral penetration. Neurotropic HIV-1 likely develops distinct genotypic characteristics in response to this unique environment.

We reviewed the literature on pediatric neuroAIDS and identified gaps in the current knowledge.

Section snippets

Pediatric HIV/AIDS epidemic

The HIV/AIDS epidemic continues to grow in most countries and continents. Globally, 40.3 million people were estimated to be living with HIV/AIDS by the end of the year 2005. An estimated 2.3 million children are living with HIV/AIDS, almost 2000 children are infected with HIV each day, and more than 1500 children die each day of HIV/AIDS.1 Global commitment to rapidly scale up the access to antiretroviral therapy (ART) has led to remarkable progress, although with less success in the provision

Neuropathogenesis of HIV-1

Notwithstanding the fact that young children may be more vulnerable to neurological complications of HIV-1 infection, the vast majority of studies into the mechanisms of HIV-1 neuropathogenesis have focused on adults with HIV-associated dementia. It has been well established that HIV-1 invades the CNS early in infection, primarily via infected monocytes/macrophages and CD4+ T lymphocytes.4, 5, 6, 7, 8, 9, 10 Macrophage-tropic forms of HIV-1 preferentially infect the brain,11, 12 and most HIV-1

HIV-related CNS disease

Since the first reports of pediatric AIDS in the 1980s, neurodevelopmental abnormalities have been a well-known complication of HIV disease and cause of significant morbidity and mortality.44, 45 In contrast to adults, where HIV attacks a mature brain and leads to dementia, HIV infection in children impacts on an immature brain and manifests as static or progressive HIV encephalopathy. The symptoms of progressive HIV-1 encephalopathy (PHE) consist of the classic triad of acquired microcephaly,

Pediatric NeuroAIDS: experiences in developing countries

It is highly unlikely that the data from the US and Europe are directly applicable to other parts of the world, because of differences in substance abuse in HIV-infected pregnant women, in prevalence of malnutrition and opportunistic infections, and in child-rearing environment.114 It is therefore surprising that, even though more than 90% of HIV-infected children live in the developing world, few studies have investigated the neurological manifestations of HIV-infected children outside of the

Challenge of defining the CNS burden attributable to HIV infection in children

The determination of whether a child's neurobehavioral deficit is related to HIV disease as opposed to other medical, environmental or social factors is critical.88, 125, 126 Low levels of maternal literacy, poor socio-economic status, poor quality of interaction between caregivers and child, low birth weight and anemia may all be more frequent in HIV-infected children. In developing countries, zinc deficiency, protein malnutrition and childhood encephalopathies such as cerebral malaria and

Conclusion

Whereas the pediatric HIV/AIDS epidemic in the US and Europe is virtually eliminated, the problem in other regions of the world, especially sub-Saharan Africa, is still growing. Neurodevelopmental delay is clearly associated with HIV infection, and exposure to the virus in utero may also have an impact on children's development. Access to PMTCT for all pregnant women and universal access to ART for all eligible children is thus urgently needed.

PHE is the most common CNS disorder among

Acknowledgements

A.V.R. is supported by grant FIC/NIMH R21 TW06682; P.R.H. by grants R01-MH067751 and a Lineberger Cancer Center postdoctoral training fellowship, K.R. by Grants A125868, MH067751, MH632690, NIMH 5199/AI038858. A.V.R., P.R.H. and K.R. are also supported by the UNC CFAR.

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    Copyright © 2006 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.