Abstract
Mutations at amino acids 143, 148, and 155 in HIV-1 integrase (IN) define primary resistance pathways in subjects failing raltegravir (RAL)-containing treatments. Although each pathway appears to be genetically distinct, shifts in the predominant resistant virus population have been reported under continued drug pressure. To better understand this dynamic, we characterized the RAL susceptibility of 200 resistant viruses, and we performed sequential clonal analysis for selected cases. Patient viruses containing Y143R, Q148R, or Q148H mutations consistently exhibited larger reductions in RAL susceptibility than patient viruses containing N155H mutations. Sequential analyses of virus populations from three subjects revealed temporal shifts in subpopulations representing N155H, Y143R, or Q148H escape pathways. Evaluation of molecular clones isolated from different time points demonstrated that Y143R and Q148H variants exhibited larger reductions in RAL susceptibility and higher IN-mediated replication capacity (RC) than N155H variants within the same subject. Furthermore, shifts from the N155H pathway to either the Q148R or H pathway or the Y143R pathway were dependent on the amino acid substitution at position 148 and the secondar...Continue Reading
References
Feb 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·F D Bushman, R Craigie
Sep 28, 1990·Science·F D BushmanR Craigie
Nov 30, 1990·Gene·O LandtU Hahn
Jan 29, 2000·Science·D J HazudaM D Miller
Mar 18, 2000·Antimicrobial Agents and Chemotherapy·C J PetropoulosJ M Whitcomb
Oct 15, 2003·Journal of Virology·Valery FikkertMyriam Witvrouw
Jul 28, 2004·Proceedings of the National Academy of Sciences of the United States of America·Daria J HazudaSteven D Young
Dec 27, 2005·Antimicrobial Agents and Chemotherapy·Deborah J Lee, W Edward Robinson
Nov 6, 2007·Journal of Virology·Kazuya ShimuraMasao Matsuoka
Jan 30, 2008·Antimicrobial Agents and Chemotherapy·Isabelle MaletAnne-Geneviève Marcelin
Jul 25, 2008·The New England Journal of Medicine·Roy T SteigbigelUNKNOWN BENCHMRK Study Teams
Jul 25, 2008·The New England Journal of Medicine·David A CooperUNKNOWN BENCHMRK Study Teams
Jul 25, 2008·HIV Medicine·C CharpentierC Piketty
Aug 22, 2008·Journal of Virology·Olivia GoethalsKurt Hertogs
Sep 4, 2008·Journal of Medicinal Chemistry·Vincenzo SummaMichael Rowley
Jan 9, 2009·Nucleic Acids Research·Olivier DelelisJean-François Mouscadet
Feb 18, 2009·The Journal of Antimicrobial Chemotherapy·Isabelle MaletAnne-Genevieve Marcelin
Mar 17, 2009·Methods : a Companion to Methods in Enzymology·Marc Witmer, Robert Danovich
Jul 17, 2009·Journal of Virology·Romina QuerciaFrançois Clavel
Aug 5, 2009·Antimicrobial Agents and Chemotherapy·Andrea LowMartin Markowitz
Aug 12, 2009·Antimicrobial Agents and Chemotherapy·Signe FransenCharlotte Charpentier
Sep 18, 2009·Journal of Virology·Signe FransenWei Huang
Mar 20, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Hiroyu HatanoSteven G Deeks
Apr 21, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Jeffrey L LennoxUNKNOWN STARTMRK Investigators
Jul 17, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Zixin Hu, Daniel R Kuritzkes
Dec 1, 2010·Antimicrobial Agents and Chemotherapy·Masanori KobayashiTamio Fujiwara
Aug 13, 2011·AIDS·Rithun MukherjeeFrederic D Bushman
Citations
Feb 14, 2013·Antiviral Research·Luis Menéndez-Arias
Aug 11, 2012·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Mark R UnderwoodTamio Fujiwara
Jun 5, 2013·Antimicrobial Agents and Chemotherapy·Wei HuangChristos J Petropoulos
Aug 12, 2009·Antimicrobial Agents and Chemotherapy·Signe FransenCharlotte Charpentier
Nov 18, 2009·Antimicrobial Agents and Chemotherapy·Elizabeth C ReumanRobert W Shafer
Dec 25, 2012·BMC Infectious Diseases·Miłosz ParczewskiAnna Boroń-Kaczmarska
Feb 26, 2013·Retrovirology·Thibault MesplèdeMark A Wainberg
Jun 19, 2013·PloS One·Jan WeberMiguel E Quiñones-Mateu
May 27, 2014·The Journal of Antimicrobial Chemotherapy·Michela PollicitaValentina Svicher
Jun 16, 2015·Expert Opinion on Drug Metabolism & Toxicology·Andrea CalcagnoStefano Bonora
Aug 28, 2015·The Journal of Antimicrobial Chemotherapy·Tomas DoyleUNKNOWN CORONET Study Group
May 4, 2010·PloS One·Sandrine ReigadasMarie-Line Andreola
Jul 31, 2016·Journal of Virological Methods·Tomofumi NakamuraHiroaki Mitsuya
Feb 18, 2017·PloS One·Michael E AbramMichael D Miller
Jan 28, 2014·AIDS·Maureen OliveiraMark A Wainberg
Jul 29, 2017·PloS One·Roger ParedesRobert W Shafer
May 24, 2017·Antimicrobial Agents and Chemotherapy·Atsuko HachiyaYasumasa Iwatani
Nov 18, 2015·Antimicrobial Agents and Chemotherapy·Kristen N AndreattaKirsten L White
Jun 24, 2017·Sexual Health·Jodie D'CostaDoris Chibo
Jul 17, 2018·The Journal of Infectious Diseases·Wendy W ZhangAniqa Shahid
Jan 31, 2019·Expert Opinion on Pharmacotherapy·Hanh Thi Pham, Thibault Mesplède
Dec 5, 2017·Expert Opinion on Drug Safety·Rosa de MiguelJose R Arribas
Dec 18, 2012·Current Opinion in Infectious Diseases·Peter K QuashieMark A Wainberg
Feb 29, 2020·International Journal of Molecular Sciences·Arpan AcharyaGeorgette D Kanmogne
Mar 4, 2020·The Journal of Antimicrobial Chemotherapy·Daniela SánchezPaula C Aulicino
Jul 1, 2020·Antimicrobial Agents and Chemotherapy·Steven J SmithStephen H Hughes
Apr 4, 2017·The Journal of Antimicrobial Chemotherapy·Silvia RequenaUNKNOWN Spanish HIV-2 Study Group
Jun 7, 2017·Retrovirology·Kaitlin AnstettMark A Wainberg
Nov 12, 2013·Journal of Chemical Information and Modeling·Qi ChenDongqing Wei