Adolescents and HIV

Neuropsychological Functioning and Viral Load in Stable Antiretroviral Therapy-Experienced HIV-Infected Children

Study Question(s): What is the relationship between neuropsychological functioning (a combination of cognitive, neurologic, and behavioral functioning) and viral load for previously treated HIV-infected children who underwent a change in treatment regimen?

Study Participants: The study included 489 HIV-infected children, aged 4 months to 17 years, who were enrolled in two clinical trials of antiretroviral therapy. Children were required to have had at least 16 weeks of treatment with NRTIs and no experience with protease inhibitors (PIs). Children in the study had only mild or moderate immunosuppression and had not experienced a CDC class C diagnosis during the 12 months prior to the study.

Study Methods: The clinically and immunologically stable children were put into 1 of 7 drug treatment combinations, 6 of which included a PI. They were evaluated for 48 weeks with respect to changes in neuropsychological performance and viral load. The evaluations included cognitive, short-term memory, vocabulary, fine motor, behavioral, and neurologic skills.

Study Findings: At baseline, neuropsychological functioning was poorer and behavior was more problematic for HIV-infected children as compared to norms for uninfected children of the same age. Thirteen percent of children had at least 1 abnormal neurologic symptom or diagnosis. Higher viral load was associated with poorer cognitive and fine-motor scores but not with behavior ratings. PI treatment was not associated with significant improvement in any measure except vocabulary score. However, this improvement was minimal and vocabulary scores remained below age-related norms. Neuropsychological changes did not differ among the 6 PI-containing groups.

Limitations: Nine percent of children were examined in their nonprimary language. Because drug trials for HIV infection cannot recruit uninfected children of HIV-infected women, the study did not have a direct comparison group to control for environmental factors associated with neuropsychological outcomes. Environmental factors include things such as prenatal drug exposure, low level of maternal education, discordant mother-child interaction, changes in caregivers, and poverty-factors that are commonly associated with pediatric HIV infection. Also, the study was limited to 48 weeks.

Lessons Learned: The results corroborate findings from other studies indicating poorer neuropsychological functioning in children with HIV infection. However, this work contrasts with earlier results from a study of NRTI therapy in younger children that noted improvements in neuropsychological outcomes with treatment. The finding that PI-containing combination therapy reduced viral load to undetectable levels in 44% of children, but resulted in little or no improvement in neuropsychological functioning is very concerning. The provision of supportive services for young HIV-infected children and infants, such as special education, speech therapy and counseling, may play a role in improvement of neuropsychological functioning. Treatment strategies for children with HIV need to be reevaluated so that they consider restoration of neuropsychological functioning in addition to lowering viral load.

Source: Jeremy RJ, Kim S, Nozyce M, Nachman S, McIntosh K, Pelton SI, Yogev R, Wiznia A, Johnson GM, Krogstad P, Stanley K; Pediatric AIDS Clinical Trials Group (PACTG) 338 & 377 Study Teams. Neuropsychological functioning and viral load in stable antiretroviral therapy-experienced HIV-infected children. Pediatrics. 2005 Feb;115(2):380-7.