Predicting HIV disease progression in children using measures of neuropsychological and neurological functioning. Pediatric AIDS clinical trials 152 study team.

BACKGROUND: Neuropsychological testing and 2 measures of neurological status, cortical atrophy, and motor dysfunction were assessed for their usefulness in predicting human immunodeficiency virus (HIV) disease progression in infants, children, and adolescents who participated in Pediatric AIDS Clinical Trials Group Protocol 152 (PACTG 152). METHODS: A cohort of 722 antiretroviral therapy-naive children with symptomatic HIV infection were assessed at study entry and at later intervals. Assessments included neurodevelopmental testing, neuroradiologic imaging, and neurological examination of motor function. CD4 cell count and plasma RNA viral load also were measured. RESULTS: Children with the lowest neuropsychological functioning (IQ < 70) at baseline had the highest risk for later HIV disease progression (56%), compared with those with borderline/low (IQ = 70-89) functioning (26%), or with average or above (IQ > 90) functioning (18%). This was also true of week 48 neuropsychological functioning. Motor dysfunction (especially reduced muscle mass) at entry also predicted disease progression. Furthermore, motor dysfunction and week 48 neuropsychological functioning provided predictive information beyond that obtainable from surrogate markers of HIV disease status (eg, CD4 count, HIV RNA level). Children with cortical atrophy also were at higher risk for later disease progression, but when CD4 count and RNA viral load were known, cortical atrophy information provided no additional predictive information. CONCLUSIONS: Measures of neuropsychological and motor function status provide unique information regarding pediatric HIV disease progression. As such, these findings have important implications for predicting long-term outcomes (eg, longevity) in pediatric patients.

Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviral regimens. Pediatric AIDS Clinical Trials Group 152 Study Team.

OBJECTIVES: To compare the impact of three different nucleoside reverse transcriptase inhibitor regimens, zidovudine (ZDV) monotherapy, didanosine (ddI) monotherapy, and ZDV plus ddI combination therapy, on central nervous system (CNS) outcomes in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: Serial neurologic examinations, neurocognitive tests, and brain growth assessments (head circumference measurements and head computed tomography or magnetic resonance imaging studies) were performed in 831 infants and children who participated in a randomized double-blind clinical trial of nucleoside reverse transcriptase inhibitors. The Pediatric AIDS Clinical Trials Group study 152 conducted between 1991 and 1995 enrolled antiretroviral therapy-naive children. Subjects were stratified by age (3 to <30 months of age or 30 months to 18 years of age) and randomized in equal proportions to the three treatment groups. RESULTS: Combination ZDV and ddI therapy was superior to either ZDV or ddI monotherapy for most of the CNS outcomes evaluated. Treatment differences were observed within both age strata. ZDV monotherapy showed a modest statistically significant improvement in cognitive performance compared with ddI monotherapy during the initial 24 weeks, but for subsequent protection against CNS deterioration no clear difference was observed between the two monotherapy arms. CONCLUSIONS: Combination therapy with ZDV and ddI was more effective than either of the two monotherapies against CNS manifestations of human immunodeficiency virus disease. The results of this study did not indicate a long-term beneficial effect for ZDV monotherapy compared with ddI monotherapy.

Magnetic resonance spectroscopy in childhood AIDS encephalopathy.

Twenty-five children with acquired immunodeficiency syndrome (AIDS) underwent cranial magnetic resonance imaging and proton magnetic resonance spectroscopy. Patients were divided into 2 groups based on clinical parameters: encephalopathy and nonencephalopathy. N-acetyl aspartate/creatine ratios were compared between the 2 groups and to control data. Spectra were obtained for 2 volumes of interest: the basal ganglia region and the white matter. The mean basal ganglia region ratio for the AIDS encephalopathy patients (n = 8) was 1.12 and the ratio for the AIDS nonencephalopathy patients (n = 17) was 1.48. The ratio for the 9 controls was 1.57. The encephalopathy group had a significantly lower ratio than both the control (P < .001) and the AIDS nonencephalopathy group (P < .002). The mean white matter ratio for the encephalopathy group (n = 8) was 1.47 and for the AIDS nonencephalopathy group (n = 13) was 1.82 with a control (n = 6) ratio of 1.82. The encephalopathy patients had a lower white matter ratio than the nonencephalopathy (P < .05) patients but the ratio was not different than controls (P < .11). It is concluded that N-acetyl aspartate/creatine ratios are reduced in childhood AIDS encephalopathy and proton magnetic resonance spectroscopy may be helpful in defining brain human immunodeficiency virus-1 infection. However, further longitudinal studies are necessary to determine the sensitivity and specificity of this technique.

Effect of perinatally acquired human immunodeficiency virus infection on neurodevelopment in children during the first two years of life.

OBJECTIVE: To determine the timing, extent, and magnitude of neurodevelopmental problems in children with perinatal HIV infection compared to similar uninfected children of HIV-infected women and controls. METHODS: Neurodevelopmental assessments during the first 24 months of life for 21 HIV-infected children born to HIV-infected mothers, 65 seroreverted children born to HIV-infected mothers, and 95 non-HIV-infected children born to non-HIV-infected mothers were analyzed. Neurodevelopment was assessed by using the Bayley Scales of Infant Development beginning at 3 months of age. Kent Scoring Adaptation was also utilized. A two-stage Hierarchical Linear Model was used for analysis of neurodevelopmental scores. RESULTS: In the initial comparison of these three groups, infected children had significantly lower scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) than the other two groups. The HIV-infected children were further classified into HIV-infected without Centers for Disease Control-defined AIDS, those with lymphoid interstitial pneumonitis (LIP) only as their AIDS-defining illness, and children with an AIDS-defining diagnosis other than LIP in the first 24 months. The children with LIP-only AIDS and the infected children without AIDS on average were not significantly different from the seroreverters or the controls on MDI or PDI, while the children with non-LIP AIDS had significantly lower scores after 3 months of age. Analysis of the Kent scores indicated that the decrement in the non-LIP AIDS children was seen in all five functional domains. CONCLUSION: Children with serious HIV symptomatology appear to be at very high risk for serious developmental impairments, HIV-infected children not highly symptomatic have relatively normal neurodevelopment, and uninfected children of HIV-infected mothers do not appear to be adversely affected by the mother's HIV infection.

A 12-month study of the effects of oral zidovudine on neurodevelopmental functioning in a cohort of vertically HIV-infected inner-city children.

OBJECTIVE: To examine the effects of oral zidovudine on the neurodevelopmental functioning of HIV-infected children. METHODS: Oral zidovudine was administered to 54 symptomatic children with vertically transmitted HIV infection (Centers for Disease Control and Prevention class P2). All children were recruited from an inner-city pediatric HIV/AIDS outpatient clinic and ranged in age from 2 months to 12 years and 11 months (mean age, 3 years) at entry. Neurodevelopmental functioning, height and weight, and lymphocyte subpopulation data were ascertained for all the children pretherapy, and 6 and 12 months post-therapy initiation. RESULTS: Analysis of the 6- and 12-month post-initiation drug data found no significant change in neurodevelopmental functioning. Height and weight percentiles remained the same or improved in the majority of children. CD4+ cell counts declined over the treatment period with CD4+ counts < 500 x 10(6)/l observed in 15% of the children pre-therapy, and 33% after 1 year. CONCLUSION: In contrast with previously published data, the present study observed no improvement in neurodevelopmental functioning in HIV-infected children treated with oral zidovudine.

Does infant carrying promote attachment? An experimental study of the effects of increased physical contact on the development of attachment.

This study was designed to test the hypothesis that increased physical contact, experimentally induced, would promote greater maternal responsiveness and more secure attachment between infant and mother. Low-SES mothers of newborn infants were randomly assigned to an experimental group (n = 23) that received soft baby carriers (more physical contact) or to a control group (n = 26) that received infants seats (less contact). Using a transitional probability analysis of a play session at 31/2 months, it was demonstrated that mothers in the experimental group were more contingently responsive than control mothers to their infants' vocalizations. When the infants were 13 months old, the Ainsworth Strange Situation was administered. Significantly more experimental than control infants were securely attached to their mothers. We infer from these results that for low-income, inner-city mothers, there may be a causal relation between increased physical contact, achieved through early carrying in a soft baby carrier, and subsequent security of attachment between infant and mother.

The Developmental and Family Services Unit--a model AIDS project serving developmentally disabled children and their families.

This paper describes a model program that uses a multidisciplinary team to assess the developmental and psychosocial needs of HIV-infected children and their families. The objective of the program is to assess the needs of the children, in order to provide rehabilitative and psychosocial services; and to improve the quality of life by optimizing developmental functioning. The team includes developmental pediatricians, social workers, psychologists, a medical ethicist, physiatrist, psycho-educational specialist, and occupational, physical, and language therapists, each of whom perform complete evaluations. A weekly conference results in the formation of an individual Family Service Plan for each child and family. Forty children have been evaluated and are in program. Family compositions were varied and non-traditional. The disabilities and rehabilitative needs differed as well. The most frequently required services were occupational therapy and psychosocial intervention, to increase parental coping skills in handling disabled, chronically ill children. Children with HIV infection are living longer and will have serious deficits. The need to develop services to address the unique developmental and psychosocial needs of the children and families iS paramount.