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HIV is a neurotropic virus that often infects the central system, resulting in progressive HIV encephalopathy (PHE). Unlike opportunistic infections, which occur when the immune system is impaired, PHE can occur before there is significant immunosuppression.(1) Before combination antiretroviral therapy (ART) became widely available, progressive encephalopathy was reported in 21% to 35% of children infected with HIV and in 35% to 50% of children diagnosed with AIDS.(1,2) The primary neurologic signs of PHE in children include acquired microcephaly, acquired symmetric motor deficits such as paresis or pathologic reflexes, and the failure to reach age-appropriate milestones or the loss of developmental milestones previously obtained.
Early studies examining the effect of antiretroviral drugs on the development of PHE found that zidovudine monotherapy partially reversed progressive HIV encephalopathy. It was therefore expected that combination ART would result in significantly greater reductions in PHE prevalence.(3)
In this study, Chiriboga and associates report on the neurological outcomes of HIV-infected children receiving ART. They evaluated 126 perinatally infected children, who were followed for an average of 82 months; 32% were followed from the age of 3 months or younger. Most of the children were examined by a neurologist on a regular basis.
Approximately 1.6% of children in the study had active PHE during the final year of evaluation. The best predictor of PHE was viral load measured at baseline or at the time of diagnosis. The incidence of active PHE was <2% and the cumulative prevalence of arrested PHE was 10%, a rate much lower than those found in the earlier monotherapy studies. The authors attribute this reduced PHE incidence to the use of combination ART, the early identification of perinatally infected children, and the implementation of well-defined treatment recommendations based on the child's age, CD4 counts, and viral load determinations.
Patients in the study who ever had PHE also had spastic diparesis, hypotonic diparesis, microcephaly, developmental delay, and mental retardation. Many children with a diagnosis of developmental delay and microcephaly also had a history of prematurity, multiple drug exposures, fetal alcohol syndrome, and congenital cytomegalovirus, making it difficult to define the cause of their neurological symptoms. A significant proportion of the children who had ever had PHE also had attention deficit hyperactivity disorder. Of the school-age children who had ever had PHE, 30% required special-education classes.
This report is encouraging because it documents the reversibility of PHE and clinical signs of HIV with changes in therapy. However, in spite of significant recovery, children with arrested PHE had higher rates of residual cognitive and neurologic abnormalities and scholastic difficulties than did children who never had progressive HIV encephalopathy. Children with progressive HIV encephalopathy, even if they respond to combination ART, should be monitored closely, as relapse of neurologic signs can occur if HIV infection is not kept under control. The high rates of residual neurologic abnormalities for children who have had PHE suggest that these children should be closely supervised and evaluated for placement in special-education classes.
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