Publication Date:
2004-07-13
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- Wilson, Keith A A -- Tussey, Lynda -- Schleif, William A -- Gabryelski, Lori S -- Jin, Lixia -- Miller, Michael D -- Casimiro, Danilo R -- Emini, Emilio A -- Shiver, John W -- New York, N.Y. -- Science. 2004 Jul 23;305(5683):528-32. Epub 2004 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Merck Research Laboratories, Post Office Box 4, West Point, PA 19486, USA. daria_hazuda@merck.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15247437" target="_blank"〉PubMed〈/a〉
Keywords:
Acquired Immunodeficiency Syndrome/*drug therapy/*immunology/virology
;
Animals
;
Anti-HIV Agents/administration & dosage/blood/pharmacology/therapeutic use
;
CD4 Lymphocyte Count
;
CD4-Positive T-Lymphocytes/immunology
;
CD8-Positive T-Lymphocytes/immunology
;
Cells, Cultured
;
Drug Resistance, Viral
;
HIV Integrase/genetics/metabolism
;
HIV Integrase Inhibitors/administration & dosage/blood/pharmacology/therapeutic
;
use
;
HIV-1/drug effects/enzymology/genetics/*physiology
;
Immunity, Cellular
;
Integrase Inhibitors/administration & dosage/blood/pharmacology/*therapeutic use
;
Integrases/genetics/metabolism
;
Leukocytes, Mononuclear/virology
;
Macaca mulatta
;
Mutation
;
Naphthyridines/administration & dosage/blood/pharmacology/*therapeutic use
;
Simian Acquired Immunodeficiency Syndrome/*drug therapy/*immunology/virology
;
Simian Immunodeficiency Virus/drug effects/enzymology/genetics/*physiology
;
Viral Load
;
Viremia/drug therapy
;
Virus Replication/drug effects
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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