3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro.

Abstract

The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV). In this report, we describe the antiviral effects of a thymidine analogue,3'-azido-3'-deoxythymidine (BW A509U), which, as a triphosphate, inhibits the reverse transcriptase of HTLV-III/LAV. This agent blocks the expression of the p24 gag protein of HTLV-III/LAV in H9 cells following exposure to virus. The drug also inhibits the cytopathic effect of HTLV-IIIB (a virus derived from a pool of American patients) and HTLV-III/RF-II (an isolate obtained from a Haitian patient that differs by about 20% in the amino acid sequence of the envelope gene from several isolates of HTLV-III/LAV, including HTLV-IIIB, analyzed so far). 3'-Azido-3'-deoxythymidine also completely blocks viral replication as assessed by reverse transcriptase production in normal human peripheral blood mononuclear cells exposed to HTLV-IIIB. Finally, at concentrations of 3'-azido-3'-deoxythymidine that block the in vitro infectivity and cytopathic effect of HTLV-IIIB, the in vitro immune functions of normal T cells remain basically intact.

Reinfection results in accumulation of unintegrated viral DNA in cytopathic and persistent human immunodeficiency virus type 1 infection of CEM cells.

“…3 A) . The value of 25 nM AZT for 50% inhibition of virus production is in accord with inhibitory concentrations measured by p24 production (29), plaque formation (23), or cell-free reverse transcriptase activity (30) .…”

Effect of Cyclosporin A and Zidovudine on Immune Abnormalities Observed in the Murine Acquired Immunodeficiency Syndrome

“…Treatment with cyclosporin A (40 and 60/mg/kg/day) before and after infection with LP-BM5 MuLV significantly inhibited the development of immunologic and histopathologic changes characteristic of MAIDS [15]. This study extends our analysis by using cyclosporin A at lower doses either alone or combined with zidovudine, an inhibitor of retroviral reverse transcriptase [16].…”

Potent and selective activity of a new carbocyclic nucleoside analog (Carbovir: NSC 614846) against human immunodeficiency virus In vitro

“…Using human host-cellbased screening systems, it was possible to identify AZT as a candidate for development and, with unprecedented speed, enter it into clinical testing (4). In randomized placebo-controlled trials, AZT was rapidly shown to have therapeutic value and has subsequently become the "drug of choice" for treatment of AIDS (5).…”