Lack of inhibition of HIV replication in chronically infected macrophages by Tat inhibitors Ro-5-3335 and Ro-24-7429.

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Lack of inhibition of HIV replication in chronically infected macrophages by Tat inhibitors Ro-5-3335 and Ro-24-7429.

Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:100 (poster no. 51). Unique Identifier : AIDSLINE ASHM5/94348910
Dunne A; Siregar H; Sonza S; Crowe S; Macfarlane Burnet Centre for Medical Research, Fairfield; Hospital, Vic.

Abstract: 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.

Keywords: 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 ABSTRACT
941230
M94C4317

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