Document 0024
 DOCN  M9620024
 TI    Efficacy of AZT therapy in reducing p24 antigen burden in a modified
       SCID mouse model of HIV infection.
 DT    9602
 AU    Alder J; Hui YH; Clement J; Department 47T, Abbott Laboratories, Abbott
       Park, IL 60064-3500,; USA.
 SO    Antiviral Res. 1995 May;27(1-2):85-97. Unique Identifier : AIDSLINE
       MED/96075697
 AB    A modified severe combined immunodeficient (SCID) mouse model of HIV
       infection which utilized multiple reconstitutions with human lymphocytes
       and a large inoculum of HIV was investigated. This mouse model yielded
       splenic HIV p24 antigen concentrations detectable by standard clinical
       means. The concentration of p24 exceeded 600 pg/g of spleen through 4
       weeks postinfection. A 1-week course of AZT therapy initiated after
       infection produced a dose responsive reduction in p24 antigen burden. Up
       to a 95% reduction in p24 antigen burden was observed following AZT
       therapy at 50 mg/kg/day, while AZT therapy at 5 and 0.5 mg/kg/day
       produced 52 and 18% reductions. In vitro and pharmacokinetic evaluations
       correlated potency and tissue concentrations of AZT with treatment
       efficacy. Active HIV replication in the SCID mice was suggested by both
       the recovery of viable virus from SCID spleens, and by the efficacy of a
       brief course of AZT therapy. This SCID mouse model of HIV infection was
       more quantitative than previous mouse models that utilize PCR-based
       techniques for detection of HIV. The high HIV burden in this SCID mouse
       model allowed reductions in p24 concentration to be monitored in
       response to AZT therapy. A dose response to AZT therapy was
       demonstrated, even when the first dose was administered after infection.
       This result suggests greater sensitivity than in previous models in
       which pretreatment with AZT was required to produce a protective
       response. This SCID mouse model may be useful for determining efficacy
       of experimental HIV therapeutics prior to clinical use. An effective
       animal model could result in a reduction in cost and more rapid
       development of effective HIV therapeutics.
 DE    Animal  Cell Line  *Disease Models, Animal  Female  Human  HIV Core
       Protein p24/*DRUG EFFECTS/METABOLISM  HIV Infections/*DRUG
       THERAPY/VIROLOGY  Mice  Mice, Inbred BALB C  Mice, SCID
       Spleen/METABOLISM/VIROLOGY  Time Factors
       Zidovudine/*PHARMACOLOGY/PHARMACOKINETICS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).