Biomedical subjects

P Brouwers

Publications and source records attributed to P Brouwers.

At least 19 recordsLinked to original sources

PubMed2000

Methodological issues in analyzing psychological test scores in pediatric clinical trials.

Clinical trials to address drug dosing, safety, and efficacy issues in the pediatric population are becoming more common. In some studies, tests of mental ability are administered at regular intervals in drug trials for treatment of children with HIV, certain types of cancer, sickle cell anemia, and diabetes. The test scores are used to examine differences between treatments in efficacy and safety over time. In addition to the well-known problems of analyzing repeated measures with incomplete data profiles, the analyses of these data are complicated by a number of unique features, including that children can be so ill that their raw scores cannot be mapped to a normed scaled score, and that children may be in the studies long enough that they transition between the age-appropriate instruments. These issues are often ignored in data analyses and can potentially cause incorrect conclusions regarding treatment efficacy and safety. This article describes these issues and their possible consequences. A simple approach to determine their impact on the statistical analysis of a particular clinical trial is suggested. The approach is illustrated with data from a Phase III trial in HIV-infected children.

Age Factors↗

PubMed2000

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.

AIDS Dementia Complex↗

PubMed2000

Cerebrospinal fluid viral load is related to cortical atrophy and not to intracerebral calcifications in children with symptomatic HIV disease.

The relationships between viral load in plasma and cerebrospinal fluid (CSF) and computed tomography (CT) brain scan abnormalities were studied in 39 children between 0.5 and 13 years of age with symptomatic HIV-1 disease. Quantitative RNA PCR was used to determine HIV-1 RNA levels and a semiquantitative analog rating technique was used to evaluate non-contrast CT brain scans. CSF HIV-1 RNA copy number correlated significantly with CT brain scan ratings for severity of cortical atrophy (r = 0.36; P < 0.05) but not with ratings of intracerebral calcifications (r = -12; NS). The difference between these two correlations was significant (P < 0.05). Plasma HIV-1 RNA copy number did not correlate significantly with any CT brain scan ratings or with CSF viral load (r = 0.05; NS). Severity of cortical atrophy appeared to reflect the level of viral load in the CSF, supporting the notion that active HIV-1 replication in the CNS is at least in part responsible for such brain abnormalities in children. The lack of correlation of intracerebral calcifications with other CT brain scan abnormalities as well as with CSF viral load suggests that this lesion is relatively independent and may reflect a different neuropathologic process.

AIDS Dementia Complex↗

PubMed1999

Preliminary evaluation of human immunodeficiency virus type 1 (HIV-1) immunogen in children with HIV-1 infection.

The safety and preliminary activity of human immunodeficiency virus type 1 (HIV-1) immunogen were evaluated in 10 HIV-1-infected children with disease stage N1,2 or A1,2. Multiple inoculations of 2. 5 or 10 units (U) of HIV-1 immunogen were safe and well tolerated without an acceleration of disease progression. When antiretroviral agents were coadministered, the 10 U dose appeared to be associated with more sustained reduction in plasma HIV-1 RNA than the 2.5 U dose (median log10 HIV-1 RNA at month 18, 3.07 vs. 4.01 copies/mL in 10 U [n=4] vs. 2.5 U [n=3], respectively; P=.034). Levels of regulated-on-activation, normal T cell-expressed and -secreted chemokine produced from HIV-1 immunogen-stimulated lymphocytes in vitro were increased in the children who had HIV-1 immunogen-specific antibody responses (P<.02) and appeared to be inversely correlated with levels of plasma HIV-1 RNA (P<.01). These preliminary data warrant larger studies to determine the effectiveness of adjunctive therapy with HIV-1 immunogen in children with HIV-1 infection.

AIDS Vaccines↗

PubMed1999

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.

Adolescent↗

PubMed1998

A randomized study of combined zidovudine-lamivudine versus didanosine monotherapy in children with symptomatic therapy-naive HIV-1 infection. The Pediatric AIDS Clinical Trials Group Protocol 300 Study Team.

OBJECTIVE: The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 300 assessed the clinical efficacy and safety of combination zidovudine/lamivudine (ZDV/3TC) compared with either didanosine (ddI) alone or combination ZDV/ddI. STUDY DESIGN: Children with symptomatic human immunodeficiency virus (HIV) infection, 6 weeks through 15 years of age, were stratified according to age and randomly assigned to receive ddI, ZDV/3TC, or ZDV/ddI. The primary endpoint was time to first progression of HIV disease or death. Enrollment in the ZDV/ddI arm stopped after 11 months on the basis of results of PACTG Protocol 152, but blinded follow-up continued. RESULTS: For the 471 children who could be evaluated, the median age was 2.7 years, median CD4 cell count was 699 cells/mm3, and median log10 HIV RNA was 5.1/mL. Median follow-up was 9.4 months. Patients receiving ZDV/3TC had a lower risk of HIV disease progression or death than those receiving ddI alone (15 vs 38 failures, P = .0006) and a lower risk of death (3 vs 15 deaths, P = .0039). Weight and height growth rates, CD4+ cell counts, and RNA concentrations showed results favoring ZDV/3TC. For patients concurrently randomized to all 3 treatment arms, both ZDV/3TC and ZDV/ddI recipients had lower risk of HIV disease progression than those who received ddI alone (P = .0026 and P = .0045). CONCLUSIONS: Combination therapy with either ZDV/3TC or ZDV/ddI was superior, as determined by clinical and laboratory measures, to monotherapy with ddI.

Adolescent↗

PubMed1998

A preliminary study of factors associated with psychological adjustment and disease course in school-age children infected with the human immunodeficiency virus.

This study consisted of a longitudinal examination (baseline and approximately 2-yr follow-up) of factors associated with psychological adjustment in a sample of 24 school-age children infected with the human immunodeficiency virus (HIV). Measures of depression, anxiety, and self-concept were administered to the children, and measures of behavioral problems, social functioning, and negative life events were administered to the parents. Generally, psychological adjustment seemed stable, though a decrease in positive social self-concept over time was observed. Negative life events were significantly associated with greater adverse psychological and behavioral outcomes at both baseline and follow-up. An additional component to the study investigated factors associated with survival. Examination of an additional five children who died within 12 months of baseline indicated that they experienced significantly more adverse life events, were less resilient, and had greater disease progression. The sample size was small and requires that these findings be considered as preliminary and suggestive rather than conclusive.

Adaptation, Psychological↗

PubMed1998

Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.

PURPOSE: Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS: Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS: The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION: The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.

Adult↗

PubMed1998

A phase I/II study of the protease inhibitor ritonavir in children with human immunodeficiency virus infection.

BACKGROUND: Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In a phase I/II study, we assessed the safety, tolerability, and pharmacokinetic profile of the oral solution of ritonavir in HIV-infected children and studied the preliminary antiviral and clinical effects. METHODS: HIV-infected children between 6 months and 18 years of age were eligible. Four dose levels of ritonavir oral solution (250, 300, 350, and 400 mg/m given every 12 hours) were evaluated in two age groups (</=2 years, >2 years). Ritonavir was administered alone for the first 12 weeks and then in combination with zidovudine and/or didanosine. Clinical and laboratory parameters were monitored every 2 to 4 weeks. RESULTS: A total of 48 children (median age, 7.7 years; range, 0.5 to 14.4 years) were included in this analysis. Dose-related nausea, diarrhea, and abdominal pain were the most common toxicities and resulted in discontinuation of ritonavir in 7 children. Ritonavir was well absorbed at all dose levels, and plasma concentrations reached a peak 2 to 4 hours after a dose. CD4 cells counts increased by a median of 79 cells/mm3 after 4 weeks of monotherapy and were maintained throughout the study. Plasma HIV RNA decreased by 1 to 2 log10 copies/mL within 4 to 8 weeks of ritonavir monotherapy, and this level was sustained in patients enrolled at the highest dose level of 400 mg/m for the 24-week period. CONCLUSIONS: The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine.

Administration, Oral↗

PubMed1998

A phase I/II study of the protease inhibitor indinavir in children with HIV infection.

BACKGROUND: Indinavir, an inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, is approved for the treatment of HIV infection in adults when antiretroviral therapy is indicated. We evaluated the safety and pharmacokinetic profile of the indinavir free-base liquid suspension and the sulfate salt dry-filled capsules in HIV-infected children, and studied its preliminary antiviral and clinical activity in this patient population. In addition, we evaluated the pharmacokinetic profile of a jet-milled suspension after a single dose. METHODS: Previously untreated children or patients with progressive HIV disease despite antiretroviral therapy or with treatment-associated toxicity were eligible for this phase I/II study. Three dose levels (250 mg/m2, 350 mg/m2, and 500 mg/m2 per dose given orally every 8 h) were evaluated in 2 age groups (<12 years and >/=12 years). Indinavir was initially administered as monotherapy and then in combination with zidovudine and lamivudine after 16 weeks. RESULTS: Fifty-four HIV-infected children (ages 3.1 to 18.9 years) were enrolled. The indinavir free-base suspension was less bioavailable than the dry-filled capsule formulation, and therapy was changed to capsules in all children. Hematuria was the most common side effect, occurring in 7 (13%) children, and associated with nephrolithiasis in 1 patient. The combination of indinavir, lamivudine, and zidovudine was well tolerated. The median CD4 cell count increased after 2 weeks of indinavir monotherapy by 64 cells/mm3, and this was sustained at all dose levels. Plasma ribonucleic acid levels decreased rapidly in a dose-dependent way, but increased toward baseline after a few weeks of indinavir monotherapy. CONCLUSIONS: Indinavir dry-filled capsules are relatively well tolerated by children with HIV infection, although hematuria occurs at higher doses. Future studies need to evaluate the efficacy of indinavir when combined de novo with zidovudine and lamivudine.

Adolescent↗

PubMed1997

Receptive and expressive language function of children with symptomatic HIV infection and relationship with disease parameters: a longitudinal 24-month follow-up study.

OBJECTIVES: To longitudinally assess the receptive and expressive language functioning of children with symptomatic HIV disease and to explore the relationship between immune status, computed tomography (CT) brain scan abnormalities, and language dysfunction over time. METHODS: Children with symptomatic HIV infection were administered an age-appropriate standardized comprehensive language test and general cognitive measure prior to starting antiretroviral therapy (n = 44) and again after 6 months (n = 29) and 24 months (n = 17). CD4 percentage and CT brain scans were also obtained at each evaluation. RESULTS: Expressive language was significantly more impaired than receptive language at the baseline, 6- and 24-month evaluations. No significant changes over time were found in receptive or expressive language from baseline to after 6 months of antiretroviral therapy, but despite treatment, language scores declined significantly between 6 and 24 months. Overall cognitive function, however, remained stable from baseline to 24 months. Age-adjusted CD4 percentage increased significantly over the initial 6 months, then remained stable. Overall CT brain scan severity ratings did not change significantly over 24 months. CONCLUSION: Expressive language was consistently more impaired than receptive language over 24 months, further supporting an earlier finding that expressive language was differentially affected by HIV in children with symptomatic disease. Both receptive and expressive language declined significantly after 24 months despite antiretroviral therapy, although overall cognitive function remained stable. Thus, functioning in some domains may be more vulnerable to the effects of HIV and global measures of cognitive ability may mask such differential changes in specific brain functions.

Adolescent↗

PubMed1997

Spontaneous eye blinking, a measure of dopaminergic function, in children with acquired immunodeficiency syndrome.

OBJECTIVE: To investigate possible alterations in dopaminergic function in children with acquired immunodeficiency syndrome by evaluating spontaneous eye blink rate, a putative measure of central dopaminergic function. DESIGN: Evaluation of previously videotaped test sessions of a consecutive case series of 50 children (mean age, 5.2 years; range, 2-12 years) with acquired immunodeficiency syndrome. SETTING: Government medical research center. RESULTS: Intrarater reliability was high, expected co-variation of blink rate with age and concurrent mental activity were confirmed, and obtained rates were similar to published data. Higher blink rates, suggestive of increased dopaminergic function, were associated with more severe cortical atrophy (P < .05) and white matter abnormality (P < .05) on computed tomographic brain scans. The presence or severity of basal ganglia calcifications did not seem to influence blink rate. In addition, higher blink rates were associated with higher ratings of depressed affect (P < .05) and lower ratings of hyperactive behaviors (P < .05) during other test activities. CONCLUSIONS: The higher blink rates in human immunodeficiency virus-infected children with more severe cortical abnormalities suggest increased central dopamine activity compared with that in children without cortical computed tomographic brain scan abnormalities. Thus, as a result of structural brain abnormalities, neurotransmitter levels in children with acquired immunodeficiency syndrome may vary and this may be reflected in their socioemotional functioning.

AIDS Dementia Complex↗

PubMed1997

Effect of combination therapy with zidovudine and didanosine on neuropsychological functioning in patients with symptomatic HIV disease: a comparison of simultaneous and alternating regimens.

OBJECTIVE: To evaluate the effects of treatment with alternating and simultaneous regimens of zidovudine and didanosine on neuropsychological function in patients with symptomatic HIV-1 disease, focusing on patients with possible HIV-1-associated central nervous system (CNS) compromise at entry. DESIGN: Randomized non-blinded clinical trial. SETTING: Government medical research center. PATIENTS: Thirty-eight patients with symptomatic HIV-1 disease, of whom 21 had evidence of CNS compromise at entry. RESULTS: After 12 weeks of therapy, overall significant improvements in memory (P < 0.01) and focused attention (P < 0.001) were seen on both regimens. These gains, however, were largely limited to those patients with HIV-1-associated CNS compromise at entry (P < 0.05). Improvements were also noted in receptive vocabulary, reading, perceptual discrimination and reasoning, divided attention, motor strength, and in mood and affect. Improvements in those latter functions were generally of limited magnitude and were of comparable size for both compromised and non-compromised patients. There was no overall difference between the two drug regimens in the effects on CNS parameters. CONCLUSIONS: Therapy-related improvements were noted particularly for patients with HIV-1-associated CNS compromise. Neuropsychological functions that have been implicated in AIDS dementia--memory and attention--showed the greatest gains. In contrast to the previously described superiority of the simultaneous regimen with regard to immunologic and virologic parameters, there was no difference between the regimens with regard to CNS measures. This supports the contention that the CNS constitutes a relative independent compartment in terms of HIV disease and treatment.

AIDS Dementia Complex↗

PubMed1996

A novel approach to the determination and characterization of HIV dementia.

BACKGROUND: Neuropsychological studies of the pattern and extent of cognitive impairment in HIV-infected patients have mostly used deviations from control values and/or cut-off scores as criteria for classification of dementia. There is, however, no agreement as to how to define impairment, and classification is imprecise. METHOD: The current study used a dementia classification matrix, developed with a step-wise linear discriminant analysis of neuropsychological data from patients with primary neurodegenerative dementias, to classify symptomatic HIV patients as demented or non-demented, and further to differentiate cortical and subcortical dementia patterns. Thirty-two male and 2 female patients (mean age 39 +/- 2) with symptomatic HIV disease (mean absolute CD4 count 195 +/- 41) participated in the study. RESULTS: Thirty-five per cent of patients were classified as demented. Of these, 83% showed a subcortical pattern and 17% a cortical profile of deficits. Significant differences between patients classified as subcortically demented and those categorized as normal on neuropsychological measures associated with subcortical integrity further validated the classification. Measures of psychiatric status between subgroups were similar. CONCLUSION: Since certain treatments may delay or reverse cognitive deficits, the use of an objective classification method based on discriminant analysis may help to identify patients who may benefit from therapy.

AIDS Dementia Complex↗

PubMed1996

Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128). Pediatric AIDS Clinical Trials Group.

The current dosage of zidovudine for children is 180 mg/m2 every 6 h. To investigate whether a lower dosage was equally effective, human immunodeficiency virus (HIV)-infected children (3 months to 12 years) with mild to moderate symptoms were randomly assigned to receive either high-dose (180 mg/m2/dose) or low-dose (90 mg/m2/dose) zidovudine (double-blind). Treatments were compared with respect to neuropsychologic function, survival, clinical and laboratory evidence of disease progression, and safety and tolerance. Four hundred twenty-six HIV-infected children were enrolled; median time for receipt of study drug was 35 months. Zidovudine in either dose was well tolerated, with no difference in efficacy or tolerance by treatment group using any clinical or laboratory parameter. In children with mild to moderate disease, a reduction of zidovudine to 90 mg/m2/dose will result in substantial cost savings and should be the recommended dose.

AIDS Dementia Complex↗

PubMed1996

Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group.

The safety, tolerability, pharmacokinetic profile, and preliminary activity of lamivudine (2'-deoxy-3'-thiacytidine), a novel cytidine nucleoside analogue with antiretroviral activity, in human immunodeficiency virus (HIV)-infected children beyond the neonatal period were studied. Ninety children received dosages of 1-20 mg/kg/day. Pharmacokinetic evaluation demonstrated serum and cerebrospinal fluid concentrations that increased proportionally to dose. As of January 1994, 11 children had been withdrawn from study for disease progression and 10 because of possible lamivudine-related toxicity, and 6 had died. CD4 and CD8 cell counts remained stable over 24 weeks in therapy-naive children and decrease slightly in previously treated children. Quantitative immune complex-dissociated p24 antigen and HIV RNA were decreased significantly at 12 and 24 weeks. In vitro resistance to lamivudine was documented in sequential virus isolates from some patients by 12 weeks. Lamivudine was well-tolerated and exhibited virologic activity in children, although future use in children is likely to be in combination antiretroviral regimens.

Adolescent↗

PubMed1996

Evaluation of human immunodeficiency virus (HIV) type 1 RNA levels in cerebrospinal fluid and viral resistance to zidovudine in children with HIV encephalopathy.

The amount of human immunodeficiency virus (HIV) type 1 RNA and the presence of a codon 215 mutation indicative of zidovudine resistance were evaluated in cerebrospinal fluid (CSF) and plasma obtained from HIV-1-infected children. The level of HIV-1 RNA in CSF was highest in children with severe encephalopathy (n = 25; median, 430 copies/mL; range, 0-2.2 x 10(5) copies/mL) followed by the moderately encephalopathic (n = 7; median, 330; range, 0-1130) and nonencephalopathic groups (n = 9; median, 0; range, 0-566) (P = .007). There was no correlation between CSF and plasma HIV-1 RNA levels. Five of 7 children with the codon 215 mutation in CSF had a progression of encephalopathy, while all 8 children with wild type codon 215 had improved or stable disease during zidovudine treatment (P = .007). These findings suggest that increased viral replication and emergence of drug-resistant HIV-1 variants within the central nervous system may play a role in progression of HIV encephalopathy.

AIDS Dementia Complex↗

PubMed1996

Neurobehavioral manifestations of symptomatic HIV-1 disease in children: can nutritional factors play a role?

Central nervous system (CNS) abnormalities are significant and frequent complications of human immunodeficiency virus (HIV-1) infection in infants and children. Although the predominant cause of neurological and neuropsychological abnormalities appears to be related to HIV infection of the CNS, other factors including malnutrition may also play a role. We retrospectively evaluated the association of change in body weight with changes in neurocognitive function, ventricular brain ratio, and cerebrospinal quinolinic acid levels in a small cohort of children (n=15; mean age 6.3 years) with symptomatic HIV-1 disease before and after 6 months of antiretroviral therapy with continuous intravenous infusion of zidovudine (ZVD). Significant increases in weight and neurocognitive function as well as decreases in ventricular brain ratio and cerebrospinal quinolinic acid levels were noted after therapy. Only the relation between increase in weight and decrease in ventricular brain ratio was statistically significant (P< .01); contrary to expectations, an increase in weight seemed to correlate with a decrease in neurocognitive function (NS). Another group of children treated at the same time with oral intermittent ZVD, but otherwise receiving the same care did not show the same magnitude of improvement in neurocognitive function. These results seem to suggest that general supportive and medical care as well as nutritional factors may only play a limited role in the neurocognitive improvements after antiretroviral therapy with continuous infusion ZVD. Our sample size was, however, small and the nutritional measure rather global; thus these findings have to be considered as very preliminary.

Acquired Immunodeficiency Syndrome↗