title: Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques.
abstract: 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.
authors.affiliation: Department of Biological Chemistry, Merck Research Laboratories, Post Office Box 4, West Point, PA 19486, USA. daria_hazuda@merck.com
authors.forename: Daria J
authors.initials: DJ
authors.lastname: Hazuda
authors.forename: Steven D
authors.initials: SD
authors.lastname: Young
authors.forename: James P
authors.initials: JP
authors.lastname: Guare
authors.forename: Neville J
authors.initials: NJ
authors.lastname: Anthony
authors.forename: Robert P
authors.initials: RP
authors.lastname: Gomez
authors.forename: John S
authors.initials: JS
authors.lastname: Wai
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacca
authors.forename: Larry
authors.initials: L
authors.lastname: Handt
authors.forename: Sherri L
authors.initials: SL
authors.lastname: Motzel
authors.forename: Hilton J
authors.initials: HJ
authors.lastname: Klein
authors.forename: Geethanjali
authors.initials: G
authors.lastname: Dornadula
authors.forename: Robert M
authors.initials: RM
authors.lastname: Danovich
authors.forename: Marc V
authors.initials: MV
authors.lastname: Witmer
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Wilson
authors.forename: Lynda
authors.initials: L
authors.lastname: Tussey
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Lori S
authors.initials: LS
authors.lastname: Gabryelski
authors.forename: Lixia
authors.initials: L
authors.lastname: Jin
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D024882:Drug Resistance, Viral; D019427:HIV Integrase / Q000235:genetics / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D007111:Immunity, Cellular; D019429:Integrase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000821:virology; D008253:Macaca mulatta; D009154:Mutation; D009287:Naphthyridines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D019429:Integrase Inhibitors; C488294:L870812; D009287:Naphthyridines; D019427:HIV Integrase; D019426:Integrases