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).
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Delayed-Action Preparations / administration & dosage
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Delayed-Action Preparations / pharmacokinetics
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HIV Infections / prevention & control*
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HIV Integrase Inhibitors / administration & dosage*
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HIV Integrase Inhibitors / blood
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HIV Integrase Inhibitors / pharmacokinetics
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HIV-1 / drug effects*
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Humans
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Macaca mulatta
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Molecular Sequence Data
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Pyridones / administration & dosage*
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Rectum / virology
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Simian Acquired Immunodeficiency Syndrome / prevention & control*
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Simian Immunodeficiency Virus / drug effects*
Substances
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Delayed-Action Preparations
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HIV Integrase Inhibitors
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Pyridones
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cabotegravir
Associated data
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GENBANK/KJ415285
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GENBANK/KJ415286
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GENBANK/KJ415287
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GENBANK/KJ415288
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GENBANK/KJ415289
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GENBANK/KJ415290
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GENBANK/KJ415291
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GENBANK/KJ415292
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GENBANK/KJ415293
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GENBANK/KJ415294
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GENBANK/KJ415295
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GENBANK/KJ415296
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GENBANK/KJ415297