title: HIV-1 integrase inhibitor resistance and its clinical implications.
abstract: With the approval in 2007 of the first integrase inhibitor (INI), raltegravir, clinicians became better able to suppress virus replication in patients infected with human immunodeficiency virus type 1 (HIV-1) who were harboring many of the most highly drug-resistant viruses. Raltegravir also provided clinicians with additional options for first-line therapy and for the simplification of regimens in patients with stable virological suppression. Two additional INIs in advanced clinical development-elvitegravir and S/GSK1349572-may prove equally versatile. However, the INIs have a relatively low genetic barrier to resistance in that 1 or 2 mutations are capable of causing marked reductions in susceptibility to raltegravir and elvitegravir, the most well-studied INIs. This perspective reviews the genetic mechanisms of INI resistance and their implications for initial INI therapy, the treatment of antiretroviral-experienced patients, and regimen simplification.
authors: Infectious Diseases Unit, University of Barcelona, Spain.
authors: Jose-Luis
authors: JL
authors: Blanco
authors: Vici
authors: V
authors: Varghese
authors: Soo-Yon
authors: SY
authors: Rhee
authors: Jose M
authors: JM
authors: Gatell
authors: Robert W
authors: RW
authors: Shafer
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use; D000068898:Raltegravir Potassium
chemical_list: D019380:Anti-HIV Agents; D050505:Mutant Proteins; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1