title: Resistance to HIV integrase strand transfer inhibitors: in vitro findings and clinical consequences.
abstract: Three integrase strand transfer inhibitors have now been approved for the treatment of HIV infection, raltegravir, cobicistat-boosted elvitegravir, and dolutegravir. Each of these agents selects for unique signature mutations; however, there can be significant cross resistance among all three drugs when multiple mutations are present or are presented in the context of different genetic backgrounds such as non B-subtypes. Many of the mutations that are associated with integrase inhibitor resistance have a profound effect on integrase function and viral replication and thus, while only one or two mutations may be sufficient to impact susceptibility, virologic failure and treatment-associated resistance have been infrequent with all three drugs to date.
authors.affiliation: Merck and Company, 770 Sumneytown Pike, West Point, PA, United States.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Grobler
authors.affiliation: Merck and Company, 770 Sumneytown Pike, West Point, PA, United States. Electronic address: daria_hazuda@merck.com.
authors.forename: Daria J
authors.initials: DJ
authors.lastname: Hazuda
mesh_terms: D024882:Drug Resistance, Viral; D006678:HIV / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D019427:HIV Integrase / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D006801:Humans; D020125:Mutation, Missense; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D000068898:Raltegravir Potassium; D014774:Virulence; D014779:Virus Replication; D000099226:Dolutegravir
chemical_list: D019427:HIV Integrase; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones; D015363:Quinolones; D000068898:Raltegravir Potassium; D000099226:Dolutegravir; C509700:elvitegravir