A multicenter Phase II clinical trial indicates that oral AZTtreatment is safe for children with advanced AIDS.
The study also reports that children treated with AZT showimprovements similar to those seen in adults.
Dr. Ross E. McKinney of Duke University School of Medicine inDurham, N.C., led the 88-patient study reported in today's NewEngland Journal of Medicine. Sponsors of the trials were theAIDS Clinical Trials Group, the National Institute of Allergy andInfectious Diseases, the National Cancer Institute andBurroughs Wellcome Co. Wellcome's AZT (azidothymidine,zidovudine) is the only Food and Drug Administration-approved AIDS treatment.
The children, ranging in age from 4 months to 11 years,tolerated AZT as well as adults did. Some children requiredblood transfusions or dose modifications for AZT-inducedanemia.
The survival probability for AZT-treated children was 89percent after 24 weeks of therapy and 79 percent after 52weeks. Children receiving AZT gained weight, had reducedvirus levels in their serum and cerebral spinal fluid, andshowed transitory improvement in T cell CD4 counts. CD4receptors, by which HIV-1 enters cells, are key directors of theimmune response.
The children, like adults, continued to suffer from opportunisticinfections.
HOW AIDS SUPPRESSES IMMUNE SYSTEM
Researchers at the Fred Hutchinson Cancer Research Center inSeattle have identified a means by which the AIDS virussuppresses the immune system.
White blood cells expressing HIV-1's nef gene have fewer CD4receptors on their cell surfaces than cells not expressing nef, anarticle in today's issue of Nature reports.
CD4 receptors not only are the molecules through which HIV-1enters the cell, but also are key directors of the immuneresponse. Loss of CD4 receptors by T cell white blood cellstriggers the onset of AIDS immunological defects.
An understanding of the mechanism by which nef decreasesthe number of CD4 receptors on the cell surface may lead tonew therapeutic approaches against AIDS. Until now, nef's rolehas been unclear.
The authors speculate that a decrease in CD4 receptorspromotes the survival and spread of HIV-1 because fewerreceptors prevent superinfection by other viruses. In addition,T cells with reduced numbers of CD4 receptors cannot combatHIV infection.
The Seattle team does not yet know how nef downregulates theCD4 receptor. The scientists report that nef does not inhibit thesynthesis of CD4 RNA or CD4 protein. Somehow nef apparentlyprevents CD4 from crossing the cell membrane to reach andbind to the cell surface. -- Carol Talkington Verser, Ph.D.
-- Carol Talkington Verser, Ph.D. Special to BioWorld
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