Integrase Inhibitors and Cellular Immunity Suppress Retroviral Replication in Rhesus Macaques

We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in rhesus macaques infected with the simian-human immunodeficiency virus (SHIV) 89.6P. When initiated before CD4 cell depletion, L-870812 therapy mediated a sustained suppression of viremia, preserving CD4 levels and perm...

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Veröffentlicht in:	Science (American Association for the Advancement of Science) 2004-07, Vol.305 (5683), p.528-532
Hauptverfasser:	Hazuda, Daria J., Young, Steven D., Guare, James P., Anthony, Neville J., Gomez, Robert P., Wai, John S., Vacca, Joseph P., Handt, Larry, Motzel, Sherri L., Klein, Hilton J., Dornadula, Geethanjali, Danovich, Robert M., Witmer, Marc V., Keith A. A. Wilson, Tussey, Lynda, Schleif, William A., Gabryelski, Lori S., Jin, Lixia, Miller, Michael D., Casimiro, Danilo R., Emini, Emilio A., Shiver, John W.
Format:	Artikel
Sprache:	eng
Schlagworte:	Acquired Immunodeficiency Syndrome - drug therapy Acquired Immunodeficiency Syndrome - immunology Acquired Immunodeficiency Syndrome - virology Animals Anti-HIV Agents - administration & dosage Anti-HIV Agents - blood Anti-HIV Agents - pharmacology Anti-HIV Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiretrovirals Antiviral agents Antivirals Biological and medical sciences CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - immunology Cells, Cultured Cellular immunity Chemotherapy Coding Drug Resistance, Viral Drug therapy Early Intervention HIV HIV (Viruses) HIV 1 HIV Integrase - genetics HIV Integrase - metabolism HIV Integrase Inhibitors - administration & dosage HIV Integrase Inhibitors - blood HIV Integrase Inhibitors - pharmacology HIV Integrase Inhibitors - therapeutic use HIV-1 - drug effects HIV-1 - enzymology HIV-1 - genetics HIV-1 - physiology Human immunodeficiency virus Human immunodeficiency virus 1 Immune system Immunity, Cellular Immunology Infections Inhibition Integrase inhibitors Integrase Inhibitors - administration & dosage Integrase Inhibitors - blood Integrase Inhibitors - pharmacology Integrase Inhibitors - therapeutic use Integrases - genetics Integrases - metabolism Leukocytes, Mononuclear - virology Macaca mulatta Medical sciences Monkeys & apes Mutation Naphthyridines - administration & dosage Naphthyridines - blood Naphthyridines - pharmacology Naphthyridines - therapeutic use Pharmacology. Drug treatments Physiological aspects Simian Acquired Immunodeficiency Syndrome - drug therapy Simian Acquired Immunodeficiency Syndrome - immunology Simian Acquired Immunodeficiency Syndrome - virology Simian immunodeficiency virus Simian Immunodeficiency Virus - drug effects Simian Immunodeficiency Virus - enzymology Simian Immunodeficiency Virus - genetics Simian Immunodeficiency Virus - physiology Simian/human immunodeficiency virus Viral Load Viremia Viremia - drug therapy Virus Replication - drug effects Viruses
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Zusammenfassung:	We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in rhesus macaques infected with the simian-human immunodeficiency virus (SHIV) 89.6P. When initiated before CD4 cell depletion, L-870812 therapy mediated a sustained suppression of viremia, preserving CD4 levels and permitting the induction of virus-specific cellular immunity. L-870812 was also active in chronic infection; however, the magnitude and durability of the effect varied in conjunction with the pretreatment immune response and viral load. These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections.
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.1098632