Document 0745
 DOCN  M94A0745
 TI    Lack of inhibition of HIV replication in chronically infected
       macrophages by Tat inhibitors Ro-5-3335 and Ro-24-7429.
 DT    9412
 AU    Dunne A; Siregar H; Sonza S; Crowe S; Macfarlane Burnet Centre for
       Medical Research, Fairfield; Hospital, Vic.
 SO    Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:100 (poster no. 51).
       Unique Identifier : AIDSLINE ASHM5/94348910
 AB    OBJECTIVE: HIV infects different cell types including CD4+ lymphocytes
       and monocyte/macrophages (Mphi). We have examined the effect of the Tat
       inhibitors Ro-5-3335 and Ro-24-7429 in cultured human peripheral Mphi.
       METHODS: MO were isolated from HIV seronegative donors by gradient
       centrifugation and plastic adherence. Cells were infected with HIV Ba-L
       for 3 hours (acute infection) or 14 days (chronic infection) prior to
       addition of drug. Inhibition of HIV replication by each drug was
       assessed by quantitation of HIV p24 in supernatant and HIV RNA analysis.
       RESULTS: Ro-5-3335 (10 microM) and Ro-24-7429 (10 microM) resulted in
       73-80% and 92-100% inhibition respectively of acute infection with a
       clear dose response curve; chronically infected Mphi were less
       susceptible to these drugs with both compounds at 10 microM having < 50%
       inhibitory effect. RNA slot blot analysis of acutely infected Mphi
       showed inhibition of HIV mRNA by Ro-24-7429 at a concentration of 10
       microM. Viability of cells at tested concentrations was > 90%.
       CONCLUSION: The Tat inhibitors were effective in inhibiting acute HIV
       infection in Mphi but not in chronically infected cells, findings which
       differ from published studies using T cell lines. Comparative studies
       are underway to investigate the effect of these compounds in acutely and
       chronically infected T cell lines.
 DE    Antiviral Agents/*PHARMACOLOGY  Benzodiazepines/*PHARMACOLOGY
       Benzodiazepinones/*PHARMACOLOGY  Cells, Cultured  Gene Products,
       tat/*ANTAGONISTS & INHIB  Human  HIV/*DRUG EFFECTS
       Macrophages/*MICROBIOLOGY  Pyrroles/*PHARMACOLOGY  Virus
       Replication/*DRUG EFFECTS  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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