Efficacy of constant infusion of A-77003, an inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, in limiting acute HIV-1 infection in vitro.

Antimicrobial Agents and Chemotherapy
J A BilelloG L Drusano

Abstract

A-77003, a human immunodeficiency virus type 1 (HIV-1) protease inhibitor, is effective for both acute and chronic infection in vitro and was evaluated clinically by continuous intravenous infusion administration. The minimum effective dose (the concentration required to completely inhibit viral replication) was determined in vitro in a population of uninfected (99%) and HIV-infected (1%) cells exposed to A-77003 by continuous infusion in hollow-fiber bioreactors. The production of infectious HIV and release of p24 antigen from infected cells were completely inhibited in cultures exposed to A-77003 at or above a concentration of 0.5 microM. Measurement of unintegrated HIV-1 DNA synthesis and flow cytometric analysis for cells expressing HIV p24 antigen demonstrated that the spread of HIV to uninfected cells was also blocked at 0.5 microM A-77003. Dose deescalation to 0.25 microM or removal of A-77003 resulted in the limited spread of the virus throughout the culture, the resumption of viral DNA synthesis, and release of p24. HIV produced after exposure to 0.5 microM A-77003 was noninfectious for a period of 72 h after the removal of the drug. Addition of 1 mg of alpha 1-acid glycoprotein per ml to this in vitro system completel...Continue Reading

References

Oct 1, 1990·Journal of Medicinal Chemistry·D J KempfA Craig-Kennard
Feb 28, 1989·Biochemical and Biophysical Research Communications·J M LouisS Oroszlan
Aug 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·H G GöttlingerW A Haseltine
Jan 1, 1988·Annual Review of Biochemistry·H G Kräusslich, E Wimmer
Jul 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·N E KohlI S Sigal
Dec 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·C DebouckM Rosenberg
Jun 14, 1967·Journal of Molecular Biology·B Hirt
Jun 1, 1994·AIDS Research and Human Retroviruses·S KageyamaH Mitsuya
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·A H KaplanR Swanstrom
Jan 1, 1993·Annual Review of Biochemistry·A Wlodawer, J W Erickson

❮ Previous
Next ❯

Citations

May 26, 2010·Antimicrobial Agents and Chemotherapy·Ashley N BrownGeorge L Drusano
Jan 18, 2002·Antimicrobial Agents and Chemotherapy·G L DrusanoJ A Bilello
May 14, 2011·Antiviral Chemistry & Chemotherapy·James J McSharry, George L Drusano

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.