A Study of Azidothymidine in HIV-Infected Children

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 30, 2001

Keywords

ClinConnect Summary

One of the most serious effects of HIV disease in children is neuropsychological deterioration (relating to mental and nervous system functioning). This complication affects the vast majority of HIV infected children. A previous study of continuous intravenous administration of AZT in pediatric patients with HIV infection showed consistent and dramatic improvements of symptoms in all patients that had shown neurodevelopmental deficits or abnormalities. These improvements were seen within 3 to 4 weeks after AZT treatment was started. Neurodevelopmental improvements have been sustained on AZT...

Gender

ALL

Eligibility criteria

• • Inclusion Criteria
• Concurrent Medication:
• Allowed:
• • Steroids for children with lymphocytic interstitial pneumonitis (LIP) who are steroid dependent.
• • Maintenance amphotericin B and antituberculosis chemotherapy.
• • Immunoglobulin therapy for children who develop at least three serious bacterial infections while receiving zidovudine (AZT) therapy.
• • Prophylactic therapy for children who have had a previous episode of Pneumocystis carinii pneumonia (PCP) and who are receiving such therapy.
• AMENDED 07/07/93:
• • Only HIV-related encephalopathy patients eligible (i.e., children with progressive encephalopathy who have received a minimum of 3 months of oral or intermittent AZT or who have failed to improve following 6 months of optimal AZT).
• ORIGINAL DESIGN:
• • Eligibility criteria used are similar to those being used in the "Multicenter Trial to Evaluate Oral Retrovir in the Treatment of Children with Symptomatic HIV Infection," currently Protocol 88 C-92a.
• Children are included:
• • With overt encephalopathy as well as those who may have a subclinical cognitive impairment.
• • Children must have laboratory evidence of HIV infection as demonstrated by either a positive viral culture (blood or cerebrospinal fluid) or detectable serum P24 antigen or repeatedly positive test for HIV antibody. HIV antibody must be determined by federally licensed ELISA test and confirmed by Western blot.
• * Children with AIDS or ARC must have at least one of the following laboratory criteria indicative of immunologic abnormality:
• • Hypergammaglobulinemia (IgG or IgA) defined as immunoglobulin values greater than upper limit of the age-adjusted normal.
• • Hypogammaglobulinemia (IgG or IgA) defined as immunoglobulin levels less than lower limit of the age-adjusted normal.
• • Absolute depression in CD4+ cells of 500 cells/mm3 or less.
• • Decreased helper/suppressor ratio of 1.0 or less.
• • Depressed in vitro mitogen response to at least one antigen (pokeweed, phytohemagglutinin, concanavalin A, Staphylococcus aureus, tetanus toxoid, Candida).
• • Parent or guardian available to give written informed consent.
• Prior Medication:
• Allowed within 4 weeks of study entry:
• • Immunoglobulin for thrombocytopenia.
• • Exclusion Criteria
• Co-existing Condition:
• Patients with the following are excluded:
• • Serious bacterial, fungal, or parasitic infections requiring parenteral therapy, at the time of study entry.
• Concurrent Medication:
• Excluded:
• • Clofazimine, ansamycin (or other experimental agents or agents that may modify zidovudine (AZT) toxicity or safety) for active chronic opportunistic infection at time of study entry.
• • Chronic use of drugs that are metabolized by hepatic glucuronidation (and may alter the metabolism of AZT) (e.g., acetaminophen).
• • Prophylaxis for Pneumocystis carinii pneumonia (PCP) for children who have not had a previous episode of PCP, oral candidiasis, or otitis media.
• • Immunoglobulin therapy not specifically allowed.
• Patients with the following are excluded:
• • Serious bacterial, fungal, or parasitic infections requiring parenteral therapy, at the time of study entry.
• • Lymphocytic interstitial pneumonitis (LIP) and no additional AIDS-defining indicator disease as specified in the CDC Surveillance Case Definition for AIDS.
• Prior Medication:
• Excluded within 4 weeks of study entry:
• • Other antiretroviral agents including ribavirin, HPA-23, dideoxycytosine (ddC), soluble CD4, and dideoxyadenosine (ddA) / didanosine (ddI).
• • Immunomodulating agents including steroids, interferon, isoprinosine, and IL-2 not specifically allowed.
• • Immunoglobulin not specifically allowed.
• * Excluded within 2 weeks of study entry:
• • Any other experimental therapy.
• • Drugs that cause prolonged neutropenia or significant nephrotoxicity.
• Prior Treatment:
• Excluded within 4 weeks of study entry:
• • Lymphocyte transfusion for immune reconstitution.
• * Excluded within 3 months of study entry:
• • Bone marrow transplant.
• Risk Behavior:
• Excluded:
• • Active alcohol or drug abuse.