title: Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus.
abstract: GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP).
authors.affiliation: Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10016, USA.
authors.forename: Chasity D
authors.initials: CD
authors.lastname: Andrews
authors.forename: William R
authors.initials: WR
authors.lastname: Spreen
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mohri
authors.forename: Lee
authors.initials: L
authors.lastname: Moss
authors.forename: Susan
authors.initials: S
authors.lastname: Ford
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: Kasi
authors.initials: K
authors.lastname: Russell-Lodrigue
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Bohm
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cheng-Mayer
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
authors.forename: Martin
authors.initials: M
authors.lastname: Markowitz
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D015658:HIV Infections / Q000517:prevention & control*; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D011728:Pyridones / Q000008:administration & dosage*; D012007:Rectum / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects*; D054659:Diketopiperazines
chemical_list: D003692:Delayed-Action Preparations; D019428:HIV Integrase Inhibitors; D011728:Pyridones; C584914:cabotegravir; D054659:Diketopiperazines