Highly active antiretroviral therapy (HAART) has altered the natural history of HIV disease in children, dramatically reducing mortality and the incidence of AIDS. With this increased survival, the incidence of progressive encephalopathy, a hallmark of pediatric AIDS in the pre-HAART era, has decreased greatly. Unfortunately, despite these benefits, a significant minority of HIV-infected children has evidence of ongoing CNS disease. In many, CNS disease is part of the overall progression of HIV disease in the setting of viral drug resistance, but a surprising number of HIV-infected children have CNS disease despite effective virologic control on HAART. Manifestations of CNS disease are often more subtle than the frank encephalopathy seen in the pre-HAART era but have the potential to impact profoundly upon quality of life and capacity for independent functioning. Specific markers for CNS disease, factors predictive of risk for neurological decline, and pathophysiologic mechanisms have not yet been identified in HIV-infected children.

In an exploratory fashion, we propose to study HIV-infected children with CNS disease in the HAART era in an effort a) to better define the natural history HIV-related CNS disease, b) to examine the relative contributions of viral and neuroinflammatory factors, c) to determine the anatomic changes (brain MRI) and patterns of brain metabolites (1H-MRS) associated with HIV-related CNS disease and long-term nucleoside reverse transcriptase inhibitor (NRTI) use in children, and d) to identify markers/predictors of CNS disease progression.

HIV-infected children with CNS disease will be enrolled. Serial neurologic examinations, neuropsychologic tests, neuroimaging, and CSF sampling will be performed. An improved understanding of the clinical presentation, risk factors for disease progression, virological and viral resistance profiles, (1)H-MRS findings and neuroinflammatory markers in HAART-experienced children with HIV-related CNS disease is necessary for the development of targeted therapeutic and preventive strategies against neuroAIDS in pediatric patients.

Further Study Details: 

Expected Total Enrollment:  40

Highly active antiretroviral therapy (HAART) has altered the natural history of HIV disease in children, dramatically reducing mortality and the incidence of AIDS. With this increased survival, the incidence of progressive encephalopathy, a hallmark of pediatric AIDS in the pre-HAART era, has decreased greatly. Unfortunately, despite these benefits, a significant minority of HIV-infected children has evidence of ongoing CNS disease. In many, CNS disease is part of the overall progression of HIV disease in the setting of viral drug resistance, but a surprising number of HIV-infected children have CNS disease despite effective virologic control on HAART. Manifestations of CNS disease are often more subtle than the frank encephalopathy seen in the pre-HAART era but have the potential to impact profoundly upon quality of life and capacity for independent functioning. Specific markers for CNS disease, factors predictive of risk for neurological decline, and pathophysiologic mechanisms have not yet been identified in HIV-infected children.

In an exploratory fashion, we propose to study HIV-infected children with CNS disease in the HAART era in an effort a) to better define the natural history HIV-related CNS disease, b) to examine the relative contributions of viral and neuroinflammatory factors, c) to determine the anatomic changes (brain MRI) and patterns of brain metabolites (1H-MRS) associated with HIV-related CNS disease and long-term nucleoside reverse transcriptase inhibitor (NRTI) use in children, and d) to identify markers/predictors of CNS disease progression.

HIV-infected children with CNS disease will be enrolled. Serial neurologic examinations, neuropsychologic tests, neuroimaging, and CSF sampling will be performed. An improved understanding of the clinical presentation, risk factors for disease progression, virological and viral resistance profiles, (1)H-MRS findings and neuroinflammatory markers in HAART-experienced children with HIV-related CNS disease is necessary for the development of targeted therapeutic and preventive strategies against neuroAIDS in pediatric patients.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
1. HIV disease acquired in the first decade of life.
2. Evidence of CNS disease (at least one of the following):
-Classification of encephalopathy or CNS compromise.
-Diagnosis of ADHD, bipolar disease, major depression, or psychosis
3. For children greater than 7 years, ability to give assent if developmentally appropriate.
EXCLUSION CRITERIA:
1. Inability or unwillingness to provide informed consent for subjects greater than 18 years, and inability or unwillingness of one parent / legal guardian to provide consent for subjects less than 18 years.
2. Clinically significant, unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgment of the Principal Investigator or Chairpersons would compromise the patient's ability to tolerate this study or is likely to interfere with the study procedures or results
Lumbar Puncture Exclusion Criteria:
1. Increased intracranial pressure (head imaging and neurologic examination to be performed prior to LP)
2. Spinal cord lesion (to be screened by neurologic examination; spine imaging if clinically indicated)
3. Platelet count less than 75,000/mm(3)
4. Abnormal PT/PTT
5. Focal suppuration at puncture site

Please refer to this study by ClinicalTrials.gov identifier  NCT00110331

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050150; 05-C-0150
Record last reviewed:  April 11, 2005
Last Updated:  May 14, 2005
Record first received:  May 5, 2005
ClinicalTrials.gov Identifier:  NCT00110331
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-05-17