Antiretrovirals have neurologic benefits in children

Combination antiretroviral therapy in HIV-infected children appears to improve neurological status in addition to suppressing viral replication, a report in the Journal of Pediatrics suggests. Moreover, the study revealed different genotypic mutations in the cerebrospinal fluid (CSF) and plasma, suggesting discordant viral evolution.

Encephalopathy in HIV-infected children occurs early in the course of the disease, and is associated with failure to reach developmental milestones, impaired brain growth, and impaired motor skills. Unlike in adults, neurologic manifestations are often the first AIDS-defining events in children with HIV.

Cynthia McCoig’s group from the University of Texas Southwestern Medical Center studied 23 HIV-infected children aged between seven months and 10 years. They were randomly assigned to 48 weeks’ treatment with abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) or lamivudine/zidovudine (3TC/ZDV).

As expected, viral load fell following treatment, with the proportion of children with a HIV RNA viral load > 2.00 log10 copies/ml falling from 83% at baseline to just 10% at week 48.

The fall in viral load was accompanied by improvements in clinical status. At baseline, 83% of the cohort had abnormalities on neurologic testing; by week 48, just 35% were found to have neurologic abnormalities. Importantly, no children showed any progression of encephalopathy.

There was no significant difference between the treatment groups in any of the study endpoints.

Among the children for whom plasma and cerebrospinal fluid (CSF) genotypic data were available, eight of 11 (73%) had identical genotypes in both samples at baseline, but by week 48 only one of nine (11%) children had similar patterns.

“The presence of different mutation patterns associated with resistance suggests that the two compartments are influenced independently,” comment McCoig et al. “If this is the case, it is possible that antiretroviral agents have different pharmacokinetic properties within each compartment.”

These results raise the possibility that antiretroviral treatment in children should include agents with activity in the central nervous system, the authors conclude.