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lüll HIV-1 integrase inhibitor resistance and its clinical implications Blanco JL; Varghese V; Rhee SY; Gatell JM; Shafer RWJ Infect Dis 2011[May]; 203 (9): 1204-14With 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.|*Drug Resistance, Viral[MESH]|Anti-HIV Agents/*pharmacology/therapeutic use[MESH]|HIV Infections/*drug therapy/*virology[MESH]|HIV Integrase/*genetics/metabolism[MESH]|HIV-1/*drug effects/isolation & purification[MESH]|Humans[MESH]|Mutant Proteins/genetics/metabolism[MESH]|Pyrrolidinones/*pharmacology/therapeutic use[MESH]|Raltegravir Potassium[MESH] |