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.
AUTOR(ES)
Bilello, J A
RESUMO
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 completely ablated the anti-HIV effect of 0.5 microM A-77003. These data suggest that determination of the minimum effective dose under conditions which simulate human pharmacodynamic patterns may be useful in determining the initial dose and schedule for clinical trials. However, other factors, such as serum protein binding, may influence the selection of a therapeutic regimen.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=162977Documentos Relacionados
- Activities of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro.
- Human immunodeficiency virus type 1 (HIV-1) protein Vif inhibits the activity of HIV-1 protease in bacteria and in vitro.
- Human monoclonal antibodies to the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 enhance HIV-1 infection in vitro.
- Generation and characterization of a human immunodeficiency virus type 1 (HIV-1) mutant resistant to an HIV-1 protease inhibitor.
- Antibodies to the primary immunodominant domain of human immunodeficiency virus type 1 (HIV-1) glycoprotein gp41 enhance HIV-1 infection in vitro.