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THE EFFECTS OF HIV infection on children's physical growth, psychological health, and neurodevelopment can range from mild to devastating. (1) Delays in the mental and motor development of very young [...], OBJECTIVE. We examined the effect of HIV, in combination with other important health and social factors, on the development of cognitive abilities of children perinatally exposed to HIV. METHODS. Serial cognitive assessments were performed for 117 children who were infected vertically and 422 children who were exposed to but not infected with HIV, in a multicenter, natural history, longitudinal study. Repeated-measures analyses were used to evaluate the neurocognitive development of children between the ages of 3 and 7 years, as measured by the McCarthy Scales of Children's Abilities (MSCA). RESULTS. Children with HIV infection and class C status scored significantly lower in all domains of cognitive development, across all time points, than did those who were HIV infected without an AIDS-defining illness and those who were HIV exposed but not infected. There were no significant differences between the 2 latter groups in General Cognitive Index or specific domain scores. Rates of change in cognitive development were comparable (parallel) among all 3 groups over a period of 4 years. Factors that were associated consistently and significantly with lower mean scores were HIV status, number of times an examination had been completed previously, primary language, maternal education, and gender. No factors were related to rate of change of any mean domain score. CONCLUSIONS. An early AIDS-defining illness increased the risk of chronic static encephalopathy during the preschool and early school age years. Children with HIV infection but no class C event performed as well as noninfected children in measures of general cognitive ability. No significantly different profiles of strengths and weaknesses for verbal, perceptual-performance, quantitative, or memory functioning were observed among children with or without HIV infection. A number of factors were found to have significant effects on the mean scores of children in all 3 groups; however, they were not related to the rate at which learning occurred. Key Words pediatric HIV, cognition, longitudinal Abbreviations WITS--Women and Infants Transmission Study MSCA--McCarthy Scales of Children's Abilities GCI--General Cognitive Index HAART--highly active antiretroviral therapy

ABBREVIATIONS. HIV, human immunodeficiency virus; ADHD, attention-deficit/hyperactivity disorder; WITS, Women and Infants Transmission Study; CPRS, Conners' Parent Rating Scale; CI, confidence interval. The psychological effects of human immunodeficiency virus (HIV) [...], Objective. Descriptive studies and clinical reports have suggested that human immunodeficiency virus (HIV)-positive children are at risk for behavioral problems. Inadequate control groups and sample sizes have limited the ability of investigators to consider multiple influences that place HIV-positive children at risk for poor behavioral outcomes. We examined the unique and combined influences of HIV, prenatal drug exposure, and environmental factors on behavior in children who were perinatally exposed to HIV. Methods. Participants included 307 children who were born to HIV-positive mothers (96 HIV infected and 211 seroreverters) and enrolled in a natural history, longitudinal study of women to infant HIV transmission. Caregivers completed parent behavioral rating scales, beginning when the children were 3 years old. Data were also collected on prenatal drug exposure; child age, gender, and ethnicity; caregiver relationship to child; and birth complications. Results. Multivariate analyses comparing the HIV-infected children with perinatally exposed but uninfected children from similar backgrounds failed to find an association between either HIV status or prenatal drug exposure and poor behavioral outcomes. The strongest correlates of increased behavioral symptoms were demographic characteristics. Conclusions. This study suggests that although a high prevalence of behavioral problems does exist among HIV-infected children, neither HIV infection nor prenatal drug exposure is the underlying cause. Rather, other biological and environmental factors are likely contributors toward poor behavioral outcomes. Pediatrics 2003;111:384-393; pediatric HIV infection, behavioral outcome, Conners' Parent Rating Scale.

As of December 1997, [is greater than] 7900 children with an acquired immunodeficiency syndrome (AIDS)-defining illness have been reported to the Centers for Disease Control and Prevention (CDC) in the [...]

As of December 1996, [is greater than] 7600 children have been diagnosed with acquired immunodeficiency syndrome (AIDS) in the United States.[1] Approved treatment options for human immunodeficiency virus (HIV)-infected children [...]

HIV infection in children appears to be associated with language difficulties. The language skills of 36 HIV-positive children between the ages of 1.2 and 10.8 years were evaluated. Additionally, the language skills of 10 of the HIV-positive children were compared with 10 of their HIV-negative siblings. Prior to the study, 21 of the HIV-positive children had been classified as having an abnormal brain condition. Expressive language function, in which there is an inability to form words, was significantly impaired in HIV-positive children. HIV-positive children with an identified brain abnormality scored lower on expressive language function tests than HIV-positive children without an identified brain abnormality. However, the average scores between the two groups were similar. The HIV-negative siblings scored higher on measures of both expressive and receptive language. Receptive skills are those needed to understand language., Objectives. To investigate the effect of HIV disease on the receptive and expressive language of children and the relationship between CT scan brain abnormalities and language functioning. Methods. Thirty-six children (mean age, 5.5 years; range, 1 through 10 years; 75% vertical transmission; 58% classified as encephalopathic) with symptomatic HIV infection and 20 uninfected siblings (mean age, 7.8 years; range, 3 through 15 years) were administered an age-appropriate comprehensive language test assessing both receptive and expressive language (Reynell Developmental Language Scales or Clinical Evaluation of Language Fundamentals--revised). Each HIV-infected child had a CT scan of the brain as part of the baseline evaluation, which was rated independently and blindly by two neurologists, for presence and severity of brain abnormalities using a semiquantitative rating system. Results. Expressive language was significantly more impaired than receptive language in the overall sample of HIV-infected children. The encephalopathic children scored significantly lower than the non-encephalopathic children, however, the degree of discrepancy between mean receptive and expressive language scores was not significantly different between these two groups. The uninfected sibling control group did not have a significant discrepancy between receptive and expressive language, and they scored significantly higher than the infected patient group. Greater severity of CT scan abnormalities was significantly correlated with poorer receptive and expressive language functioning in the overall HIV-infected sample and a higher discrepancy between receptive and expressive language in the encephalopathic group. Conclusion. Pediatric HIV disease is associated with differential receptive and expressive language functioning in which expressive language is significantly more impaired than receptive language. The sibling data and CT scan correlations suggest that the observed language impairments are associated with the direct effects of HIV-related central nervous system disease. Pediatrics 1995;95:112-119; pediatric AIDS, HIV infection, neuropsychology, language, encephalopathy, CT scan.

Oral didanosine treatment appears to improve CD4 cell counts over the long term in some children with HIV infection. Didanosine is also known as DDI. CD4 cells are component of the immune system and are measured to evaluate immune system functioning. A group of 103 children with HIV infection, ranging in age from 6 months to 18 years, underwent didanosine therapy. Children had symptomatic HIV infection or a CD4 count of less than 500. Median length of therapy was 23 months. The CD4 count increased in 32% of patients after six months of therapy. Forty-one percent of these children improved CD4 counts for three years. The probability of survival for the 51 children with CD4 counts greater than 100 at the beginning of the study was 80% versus 39% for children with CD4 counts below that level. Treatment was discontinued in 11 children because of side effects and in 34 because of disease progression despite treatment., Background. Didanosine has demonstrated promising antiviral activity and a tolerable toxicity profile in short term studies. We describe a cohort of HIV-infected children who were treated for a prolonged period of time with didanosine. Methods. Children (6 months to 18 years of age) with symptomatic HIV infection or an absolute CD4 count < 0.5 x [10.sup.9] cells/L, received oral didanosine at doses between 20 mg/[m.sup.2] to 180 mg/[m.sup.2] every 8 hours. Clinical, immunological, and virological parameters were assessed at least every 2 months. The pharmacokinetics of didanosine were evaluated in 85 patients. Results. Previously untreated children (n = 51) and children who had received prior antiretroviral therapy (n = 52) were enrolled in the study (median time on study 22.6 months, range 2 to 48). The long-term administration of didanosine was well tolerated and no new toxicities were observed. The absolute CD4 count increased by [greater than or equal to] .05 x [10.sup.9] cells/L in 28 of 87 (32%) of patients after 6 months of therapy. Responses were also sustained in 41% of these children after 3 years of therapy. Children entering the study with a CD4 count > 0.1 x [10.sup.9] cells/L (n = 51) had a marked survival advantage (P = .00002) with an estimated survival probability after 3 years of 80% compared to 39% for children with lower CD4 counts. Although the area under the curve of didanosine increased proportionally with the dose, there was considerable interpatient variability at each dose level. There was no apparent relationship between surrogate markers of clinical outcome and plasma drug concentration. Conclusions. Didanosine was well tolerated with chronic administration, and toxicities were uncommon and usually reversible. In 41% of patients, the CD4 count increased and was maintained at the higher level even after years of treatment. Pediatrics 1994;94:724-731; HIV, didanosine, survival, toxicities, CD4 counts, pharmacokinetics, child.

Combined therapy with zidovudine (AZT) and didanosine (ddI) may benefit children with HIV infections more than either drug alone. Researchers administered varied doses of combined therapy and evaluated the outcome of 49 children who were previously untreated and 12 who had prior AZT-related toxicity. The patients tolerated AZT and ddI well at all dose levels and showed no evidence of new or enhanced toxicity. Fifty-one children gained weight while on the combined therapy program. After 24 weeks, the midpoint CD4 cell count increased from 331 to 556 cells per millimeter cubed for all patients. Among the previously untreated group, cell counts increased from 386 to 726 cells per millimeter cubed. CD4 cells are immune cells that are depleted as HIV infection progresses to advanced immune deficiency disease. Of 36 samples tested for HIV, only eight were positive after combination treatment, compared to 24 at the beginning of the study., Objective. Zidovudine and didanosine are both beneficial for the treatment of human immunodeficiency virus (HIV) infection in children. Because disease progression and toxicity often limit their long-term use as single agents, new approaches to using nucleoside analogues are necessary to improve current antiretroviral therapy. Design. We conducted a phase I-Il study to evaluate the tolerance, pharmacokinetics, and antiviral activity of the combination of zidovudine and didanosine in children with HIV infection. Sixty-eight children who were either previously untreated or who had manifested hematologic toxicity on full-dose zidovudine were enrolled. Eight dose combinations were studied in the previously untreated children, with doses of zidovudine ranging from 90 to 180 mg/[m.sup.2] every 6 hours and doses of didanosine ranging from 90 to 180 mg/[m.sup.2] every 12 hours. Results. Fifty-four previously untreated HIV-infected children were enrolled in this part of the study, of whom 49 remained in the study for a minimum of 24 weeks. For children with previous zidovudine-related hematologic toxicity, three dose levels with zidovudine at 60 mg/[m.sup.2] every 6 hours orally and didanosine ranging from 90 to 180 mg/[m.sup.2] every 12 hours orally were used. A total of 14 children were enrolled in this part of the study, and 12 remained on therapy for at least 24 weeks. No evidence of new or enhanced toxicity was observed in either group. After 24 weeks, the median CD4 cell count for all patients increased from 331 to 556 cells/[mm.sup.3] (P = .01). For the previously untreated group, the median increase in CD4 counts was from 386 to 726 cells/[mm.sup.3] (P = .003). The median p24 antigen concentration (in those with a detectable level at baseline) decreased from 95 to

OBJECTIVES. The purpose of this work was to examine the effects of HIV infection and the impact of highly active antiretroviral treatment with protease inhibitors on neuro-developmental functioning during the [...]