Document 0002
 DOCN  M9480002
 TI    Inhibition of 3'azido-3'deoxythymidine-resistant HIV-1 infection by
       dehydroepiandrosterone in vitro.
 DT    9410
 AU    Yang JY; Schwartz A; Henderson EE; Department of Microbiology and
       Immunology, Temple University; School of Medicine, Philadelphia 19140.
 SO    Biochem Biophys Res Commun. 1994 Jun 30;201(3):1424-32. Unique
       Identifier : AIDSLINE MED/94296419
 AB    Human immunodeficiency virus type 1 (HIV-1) isolated from patients with
       acquired immunodeficiency syndrome (AIDS) shows resistance to
       3'azido-3'deoxythymidine (AZT) after one or two years of treatment. AZT
       also has significant toxic side effects, further limiting its use in the
       therapy of HIV-1-infected individuals. Dehydroepiandrosterone (DHEA) has
       been shown to have a broad spectrum of biological functions, to be
       bioavailable orally and to be relatively nontoxic. Epidemiological
       studies provide evidence that reduced serum levels of DHEA are related
       to the progression of AIDS in HIV-1 infection. DHEA has also been shown
       to inhibit HIV-1 replication in vitro and block HIV-1 reactivation from
       chronically infected cell lines. However, there have been no reports on
       the ability of DHEA to inhibit the replication of AZT-resistant strains
       of HIV-1. We investigated whether DHEA treatment could inhibit
       replication of AZT-resistant strains of HIV-1. Addition of DHEA to MT-2
       cell cultures infected with either AZT-sensitive or AZT-resistant
       isolates of HIV-1 resulted in dose-dependent inhibition of HIV-1-induced
       cytopathic effect and suppression of HIV-1 replication as measured by
       accumulation of reverse transcriptase activity. At a concentration as
       low as 50 microM, DHEA reduced AZT-resistant HIV-1 replication over 50
       percent as measured by cytopathic effect and accumulation of reverse
       transcriptase activity. This study provides evidence that DHEA can
       inhibit the replication of AZT-resistant as well as wild-type HIV-1.
       Since the main targets for DHEA are metabolic and cellular signaling
       pathways leading to HIV-1 replication-activation, DHEA should be
       effective against multidrug-resistant strains of HIV-1. Combined with
       recently discovered immunoregulatory properties, the finding that DHEA
       is able to inhibit replication of both wild-type and AZT-resistant HIV-1
       suggests that in vivo DHEA may have a much broader spectrum of action
       than originally anticipated.
 DE    Cytopathogenic Effect, Viral  Drug Resistance, Microbial  Human  HIV
       Infections/*PREVENTION & CONTROL  HIV-1/*DRUG EFFECTS/GROWTH &
       DEVELOPMENT  In Vitro  Prasterone/*PHARMACOLOGY  Support, U.S. Gov't,
       P.H.S.  Tumor Cells, Cultured  Virus Replication/DRUG EFFECTS
       Zidovudine/*PHARMACOLOGY  JOURNAL ARTICLE

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