Impact of Perinatally Acquired HIV Disease Upon Longitudinal Changes in Memory and Executive Functioning.

BACKGROUND: Little is known regarding effects of perinatally acquired HIV infection (PHIV) on longitudinal change in memory and executive functioning (EF) during adolescence despite the importance of these skills for independence in adulthood. METHODS: PHIV (n = 144) and perinatally HIV-exposed uninfected youth (PHEU, n = 79), ages 12-17, completed standardized tests of memory and EF at baseline and 2 years later. Changes from baseline for each memory and EF outcome were compared between PHEU and PHIV youth with (PHIV/C, n = 39) and without (PHIV/non-C, n = 105) history of CDC class C (AIDS-defining) diagnoses. Among PHIV youth, associations of baseline and past disease severity with memory and EF performance at follow-up were evaluated using adjusted linear regression models. RESULTS: Participants were primarily black (79%); 16% were Hispanic; 55% were female. Mean memory and EF scores at follow-up generally fell in the low-average to average range. Pairwise comparison of adjusted mean change from baseline to follow-up revealed significantly greater change for PHIV/non-C compared with PHEU youth in only one verbal recognition task, with a difference in mean changes for PHIV/non-C versus PHEU of -0.99 (95% CI: -1.80 to -0.19; P = 0.02). Among youth with PHIV, better immunologic status at baseline was positively associated with follow-up measures of verbal recall and recognition and cognitive inhibition/flexibility. Past AIDS-defining diagnoses and higher peak viral load were associated with lower performance across multiple EF tasks at follow-up. CONCLUSIONS: Youth with PHIV demonstrated stable memory and EF during a 2-year period of adolescence, allowing cautious optimism regarding long-term outcomes.

Associations of Memory and Executive Functioning With Academic and Adaptive Functioning Among Youth With Perinatal HIV Exposure and/or Infection.

BACKGROUND: Perinatally acquired HIV (PHIV) confers risk for neurocognitive impairment, which potentially affects school performance and functional independence of infected children. In this study, we examined the associations of 2 key neurocognitive domains, memory and executive function (EF), with academic and adaptive skills among youth with PHIV and perinatally HIV-exposed but uninfected (PHEU) youth. METHODS: Participants ages 9 to <19 years enrolled in the Pediatric HIV/AIDS Cohort Study's Memory and Executive Functioning Study completed standardized measures of reading and math. The primary caregivers completed a standardized measure of their child's adaptive behavior. Participants with PHIV, those with (PHIV/C) and without (PHIV/non-C) a Centers for Disease Control and Prevention class C diagnosis, and PHEU participants were compared. Retrospective memory (RM), prospective memory (PM), and EF were evaluated relative to outcomes using general linear regression models adjusted for sociodemographic characteristics. RESULTS: Of the participants (N = 258; mean age, 14.1 years), 46% were male, 75% were black, and 18% were Hispanic. Adjusted mean scores in math and adaptive behavior did not differ among the youth with PHIV/C (n = 45), those with PHIV/non-C (n = 128), and PHEU youth (n = 85). Youth with PHIV/C had lower adjusted mean reading scores than PHIV/non-C and PHEU youth (86.9 vs 93.8 [P = .02] and 93.2 [P = .04], respectively). There were positive associations of RM, PM, EF, and some sociodemographic characteristics with higher reading and math scores. Immediate and delayed verbal memory, delayed visual memory, PM, and some EF measures were positively associated with adaptive behavior. CONCLUSIONS: Higher-order cognitive abilities such as memory and EF seem to play a key role in academic and adaptive capacities, regardless of a child's HIV status, and might serve as intervention targets for improving functional outcomes.

Stimulant Medications and Cognition, Behavior and Quality of Life in Children and Youth with HIV.

BACKGROUND: Limited empirical investigation exists into longitudinal changes in cognition, behavior or quality of life (QOL) in children with perinatal HIV who are prescribed stimulants. METHODS: This study was an analysis of longitudinal data from children age 3-19 years, with perinatal HIV infection, with and without prescriptions for stimulant medications [prescription (PG) and comparison (CG) groups, respectively], matched on age, availability of CD4% and outcome measures of cognition, behavior and QOL. Generalized estimating equation models were used to evaluate effects of stimulant exposure on change in measured outcomes over 3 years of follow-up, adjusting for baseline levels of outcomes and relevant covariates. RESULTS: Children in both the PG (n = 132) and the CG (n = 392) obtained mean verbal and performance (nonverbal) intelligence quotients (VIQ and PIQ, respectively) in the low-average range for age. At baseline, those in PG demonstrated more frequent signs of hyperactivity, impulsivity and conduct and learning problems than those in CG (P ≤ 0.003 in unadjusted analyses). At follow-up, after adjustment for baseline functioning and other relevant covariates, there were no significant changes from baseline in VIQ or PIQ. Stimulant prescription use, however, was associated with worsening symptoms of hyperactivity (P = 0.01), impulsivity (P = 0.04), learning problems (P < 0.001) and worsening of perceived health status (P < 0.001). CONCLUSIONS: The results suggest expectations for behavioral improvement may not align well with long-term effects of stimulant prescription use on behavior and QOL in children with HIV. Further research is necessary to determine if there are subsets of children who may benefit from stimulant therapy.

Executive Functioning in Children and Adolescents With Perinatal HIV Infection.

BACKGROUND: Perinatal HIV (PHIV) infection may place youth at risk for impairments in executive functioning (EF). We examined associations of EF with HIV infection, disease severity and other factors among youth with PHIV and perinatally HIV-exposed, uninfected youth (PHEU). METHODS: Within the US-based Pediatric HIV/AIDS Cohort Study, 354 PHIV and 200 PHEU youth completed a standardized EF measure (Children's Color Trails Test, CCTT) and youth and/or caregivers completed a questionnaire measuring everyday EF (Behavior Rating Inventory of Executive Function, BRIEF). Covariates included HIV status, current and historical disease severity, demographic and caregiver variables and other cognitive measures. Analyses used linear and logistic regression and proportional odds models. RESULTS: No significant HIV status group differences were found on CCTT scores. Caregiver BRIEF ratings indicated significantly fewer problems for PHIV than PHEU youth. However, PHIV youth with past encephalopathy self-endorsed significantly greater metacognitive (ie, cognitive regulation) problems on the BRIEF and performed more slowly on the CCTT than PHEU youth. CCTT and caregiver BRIEF scores had significant associations with indicators of past and present disease severity. Both PHIV and PHEU had significantly worse scores than population means on CCTT and BRIEF; scores had significant associations with demographic covariates. CONCLUSIONS: Youth with PHIV show EF problems likely associated with risk factors other than HIV. However, cognitive slowing and self-reported metacognitive problems were evident in PHIV youth with a history of encephalopathy. Assessment and treatment of EF impairment may be important to identifying PHIV youth at particular risk for poor health and behavioral outcomes.

Impact of medications prescribed for treatment of attention-deficit hyperactivity disorder on physical growth in children and adolescents with HIV.

OBJECTIVE: To examine the relationships between physical growth and medications prescribed for symptoms of attention-deficit hyperactivity disorder in children with HIV. METHODS: Analysis of data from children with perinatally acquired HIV (N = 2251; age 3-19 years), with and without prescriptions for stimulant and nonstimulant medications used to treat attention-deficit hyperactivity disorder, in a long-term observational study. Height and weight measurements were transformed to z scores and compared across medication groups. Changes in z scores during a 2-year interval were compared using multiple linear regression models adjusting for selected covariates. RESULTS: Participants with (n = 215) and without (n = 2036) prescriptions were shorter than expected based on US age and gender norms (p < .001). Children without prescriptions weighed less at baseline than children in the general population (p < .001) but gained height and weight at a faster rate (p < .001). Children prescribed stimulants were similar to population norms in baseline weight; their height and weight growth velocities were comparable with the general population and children without prescriptions (for weight, p = .511 and .100, respectively). Children prescribed nonstimulants had the lowest baseline height but were similar to population norms in baseline weight. Their height and weight growth velocities were comparable with the general population but significantly slower than children without prescriptions (p = .01 and .02, respectively). CONCLUSION: The use of stimulants to treat symptoms of attention-deficit hyperactivity disorder does not significantly exacerbate the potential for growth delay in children with HIV and may afford opportunities for interventions that promote physical growth. Prospective studies are needed to confirm these findings.