Vih En Infantes

S
SA Jou
r

l of Child
a lt h

Neurological and neurocognitive
function of HIV-infected children
commenced on antiretroviral therapy

na

He

ARTICLE

Lara Smith, MB ChB, DCH (SA), FCPaed (SA), MMed (Paed)
Colleen Adnams, MB ChB, FCPaed (SA), BSc (Hons)
Brian Eley, MB ChB, FCPaed (SA), BSc (Hons)
Red Cross War Memorial Children’s Hospital and School of Child and AdolescentHealth, University of Cape Town

Aim: To describe neurological and neurocognitive deficits in HIV-infected children and the short-term effect of highly active
antiretroviral therapy (HAART) on the observed deficits
Methods: In this prospective study, 39 children (15 females) were evaluated before the start of HAART and 30 reassessed 6
months later. The subjects were evaluated with a range ofcognitive tests used in everyday clinical practice.
Results: At enrolment, the mean (±SD) age was 60±46 months, 17 (44%) and 22 (56%) had Centers for Disease Control (CDC)
clinical category B and C disease respectively, and 36 (92%) had severe immunosuppression. At the start of HAART no child
had cranial nerve or cerebellar dysfunction, but 13/29 (33.3%) had evidence of motor dysfunction. By 6months 1 child had
developed cerebellar dysfunction, but there was no statistically significant change in the frequency of motor dysfunction.
Mean baseline performances on cognitive testing were generally subnormal. Between 33% and 81% of the children recorded
subnormal intelligence quotients on various cognitive tests. Mean performances did not change significantly after 6 months
of HAART.Conclusion: Neurological and neurocognitive deficits are frequent in HIV-infected children. The prevalence and extent of
deficits did not change significantly in response to short-term HAART, indicating neither spontaneous improvement nor
deterioration during early treatment.
Human immunodeficiency virus (HIV) invades the central
nervous system (CNS) soon after the initial systemic infection.Three pathways have been proposed whereby the virus
breaches the blood-brain barrier and enters CNS parenchymal
tissue: (i) HIV may be carried into the brain by infected
macrophages-monocytes and/or CD4+ T lymphocytes (Trojan
horse effect); (ii) cell-free virus may pass from the vascular
compartment into brain tissue between cerebral microvascular
endothelial cells (CMVECs) or by transmigration(transcytosis)
through CMVECs; and (iii) following direct HIV infection of
the specialised endothelial cells of the blood/brain barrier or
CMVECs, newly formed HIV viral particles may be released
into the cerebral compartment.1,2 Once established within the
CNS compartment, the virus infects various cell populations,
primarily perivascular macrophages and microglia, and
activates severalcell types including macrophages, microglia
and astrocytes.2,3 The consequent inflammatory response
induces neuronal apoptotic pathways causing neuronal death
and attrition. Apoptosis may be activated by viral glycoproteins
including gp120, tat, nef, vpr and gp41, or a variety of hostderived mediators including inflammatory cytokines, free
radicals and excitatory amino acids.4 There is someevidence
suggesting that HIV may also inhibit neural progenitor cell
proliferation, negatively affecting de novo neurogenesis.5
The consequence of the above is the development of
neurological and neurocognitive manifestations.s Classically,
HIV affects the immature brain causing static or progressive
encephalopathy. Progressive encephalopathy has been
defined by the Centers for DiseasesControl (CDC), and is
characterised by microcephaly, failure to attain or loss of
neurodevelopmental milestones, or loss of intellectual ability,

108

pg.108-113.indd 108

and acquired symmetrical motor defects.6 The prevalence
of HIV encephalopathy varies from 13% to 35%, and up
to 50% of children with full-blown AIDS (CDC clinical
category C disease) have evidence of this complication.7...