title: Resistance analyses of integrase strand transfer inhibitors within phase 3 clinical trials of treatment-naive patients.
abstract: The integrase (IN) strand transfer inhibitors (INSTIs), raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG), comprise the newest drug class approved for the treatment of HIV-1 infection, which joins the existing classes of reverse transcriptase, protease and binding/entry inhibitors. The efficacy of first-line regimens has attained remarkably high levels, reaching undetectable viral loads in 90% of patients by Week 48; however, there remain patients who require a change in regimen due to adverse events, virologic failure with emergent resistance or other issues of patient management. Large, randomized clinical trials conducted in antiretroviral treatment-naive individuals are required for drug approval in this population in the US, EU and other countries, with the primary endpoint for virologic success at Week 48. However, there are differences in the definition of virologic failure and the evaluation of drug resistance among the trials. This review focuses on the methodology and tabulation of resistance to INSTIs in phase 3 clinical trials of first-line regimens and discusses case studies of resistance.
authors: Department of Clinical Virology, Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA. kirsten.white@gilead.com.
authors: Kirsten L
authors: KL
authors: White
authors: Department of Infectious Diseases, University Hospital, Hotel-Dieu, 1 Place Ricordeau, Nantes 44093, France. francois.raffi@wanadoo.fr.
authors: Francois
authors: F
authors: Raffi
authors: Department of Clinical Virology, Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA. michael.miller@gilead.com.
authors: Michael D
authors: MD
authors: Miller
mesh_terms: D017326:Clinical Trials, Phase III as Topic; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D019562:Viral Load; 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