title: Evolution and recombination of genes encoding HIV-1 drug resistance and tropism during antiretroviral therapy.
abstract: Characterization of residual plasma virus during antiretroviral therapy (ART) is a high priority to improve understanding of HIV-1 pathogenesis and therapy. To understand the evolution of HIV-1 pol and env genes in viremic patients under selective pressure of ART, we performed longitudinal analyses of plasma-derived pol and env sequences from single HIV-1 genomes. We tested the hypotheses that drug resistance in pol was unrelated to changes in coreceptor usage (tropism), and that recombination played a role in evolution of viral strains. Recombinants were identified by using Bayesian and other computational methods. High-level genotypic resistance was seen in approximately 70% of X4 and R5 strains during ART. There was no significant association between resistance and tropism. Each patient displayed at least one recombinant encompassing env and representing a change in predicted tropism. These data suggest that, in addition to mutation, recombination can play a significant role in shaping HIV-1 evolution.
authors.affiliation: Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA.
authors.forename: Binshan
authors.initials: B
authors.lastname: Shi
authors.forename: Christina
authors.initials: C
authors.lastname: Kitchen
authors.forename: Barbara
authors.initials: B
authors.lastname: Weiser
authors.forename: Douglas
authors.initials: D
authors.lastname: Mayers
authors.forename: Brian
authors.initials: B
authors.lastname: Foley
authors.forename: Kimdar
authors.initials: K
authors.lastname: Kemal
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Marc
authors.initials: M
authors.lastname: Suchard
authors.forename: Monica
authors.initials: M
authors.lastname: Parker
authors.forename: Cheryl
authors.initials: C
authors.lastname: Brunner
authors.forename: Harold
authors.initials: H
authors.lastname: Burger
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D016000:Cluster Analysis; D024882:Drug Resistance, Viral; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011995:Recombination, Genetic; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014764:Viral Proteins / Q000235:genetics*; D056189:Viral Tropism / Q000187:drug effects*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D014764:Viral Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus
references.citation: AIDS. 2008 Nov 12;22(17):2393-5
references.pmid: 18981780
references.citation: Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905
references.pmid: 12019106
references.citation: J Virol. 2000 Feb;74(3):1234-40
references.pmid: 10627533
references.citation: Bioinformatics. 2006 Dec 15;22(24):3096-8
references.pmid: 17110367
references.citation: Clin Infect Dis. 1999 Dec;29(6):1423-30
references.pmid: 10585790
references.citation: Curr Top Microbiol Immunol. 2006;303:97-120
references.pmid: 16570858
references.citation: J Virol. 2003 May;77(9):5540-6
references.pmid: 12692259
references.citation: Biometrics. 2003 Sep;59(3):505-11
references.pmid: 14601751
references.citation: Curr HIV Res. 2009 Jan;7(1):30-8
references.pmid: 19149552
references.citation: JAMA. 2006 Aug 16;296(7):815-26
references.pmid: 16905787
references.citation: J Leukoc Biol. 2006 Nov;80(5):965-72
references.pmid: 16923919
references.citation: J Virol. 1999 Aug;73(8):6680-90
references.pmid: 10400765
references.citation: J Virol. 2004 Aug;78(16):8761-70
references.pmid: 15280484
references.citation: J Antimicrob Chemother. 2009 Jan;63(1):7-10
references.pmid: 18984648
references.citation: AIDS. 2008 Feb 19;22(4):469-79
references.pmid: 18301059
references.citation: Retrovirology. 2009 Jun 03;6:54
references.pmid: 19493346
references.citation: J Biol Chem. 2004 Aug 27;279(35):36625-32
references.pmid: 15218022
references.citation: J Virol. 2006 Jan;80(2):999-1014
references.pmid: 16379001
references.citation: J Virol. 2006 Mar;80(5):2472-82
references.pmid: 16474154
references.citation: J Virol. 2006 Nov;80(21):10591-9
references.pmid: 16956948
references.citation: N Engl J Med. 1999 May 27;340(21):1614-22
references.pmid: 10341273
references.citation: AIDS. 2003 Sep 26;17(14):2025-33
references.pmid: 14502005
references.citation: Cell. 2001 Feb 23;104(4):469-72
references.pmid: 11239404
references.citation: J Virol. 2007 Apr;81(7):3369-76
references.pmid: 17251288
references.citation: J Virol. 2008 Apr;82(8):3952-70
references.pmid: 18256145
references.citation: J Infect Dis. 2004 Apr 15;189(8):1452-65
references.pmid: 15073683
references.citation: J Virol. 1997 Mar;71(3):2059-71
references.pmid: 9032338
references.citation: J Acquir Immune Defic Syndr. 2009 Jan 1;50(1):9-18
references.pmid: 19295330
references.citation: Bioinformatics. 2005 Jul 1;21(13):3034-42
references.pmid: 15914546
references.citation: J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):34-40
references.pmid: 16123679
references.citation: J Virol. 2001 Sep;75(18):8842-7
references.pmid: 11507229
references.citation: J Virol. 1999 Jan;73(1):152-60
references.pmid: 9847317
references.citation: J Virol Methods. 1998 Dec;76(1-2):139-48
references.pmid: 9923748
references.citation: J Virol. 2005 Jan;79(1):353-63
references.pmid: 15596829
references.citation: J Allergy Clin Immunol. 2008 Jul;122(1):22-8
references.pmid: 18602567
references.citation: J Clin Invest. 2005 Nov;115(11):3250-5
references.pmid: 16276421
references.citation: AIDS. 2004 Jan 23;18(2):153-9
references.pmid: 15075531
references.citation: J Virol. 2002 Nov;76(22):11273-82
references.pmid: 12388687
references.citation: J Virol. 2002 Jan;76(2):707-16
references.pmid: 11752161
references.citation: J Virol. 2004 Oct;78(20):11296-302
references.pmid: 15452249
references.citation: J Virol. 2002 Nov;76(21):11104-12
references.pmid: 12368352
references.citation: J Infect Dis. 2000 Mar;181(3):946-53
references.pmid: 10720517
references.citation: N Engl J Med. 1999 May 27;340(21):1605-13
references.pmid: 10341272
references.citation: J Virol. 1999 May;73(5):3764-77
references.pmid: 10196271
references.citation: J Acquir Immune Defic Syndr. 2006 Jan 1;41(1):59-62
references.pmid: 16340474
references.citation: JAMA. 2001 Jul 11;286(2):196-207
references.pmid: 11448283
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1269-74
references.pmid: 10655520
references.citation: J Virol. 2002 Sep;76(18):9465-73
references.pmid: 12186928
references.citation: Nature. 2002 Jul 11;418(6894):144
references.pmid: 12110879
references.citation: Lancet. 1999 Mar 13;353(9156):863-8
references.pmid: 10093977
references.citation: J Infect Dis. 2007 Feb 15;195(4):535-45
references.pmid: 17230413
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10948-53
references.pmid: 11005867
references.citation: J Virol. 1992 Apr;66(4):2232-9
references.pmid: 1548759
references.citation: J Virol. 1997 Oct;71(10):7478-87
references.pmid: 9311827
references.citation: Science. 1995 Jan 27;267(5197):483-9
references.pmid: 7824947
references.citation: Virology. 2001 Sep 15;288(1):51-62
references.pmid: 11543657
references.citation: J Virol. 2002 Nov;76(21):10674-84
references.pmid: 12368309
references.citation: J Virol. 2005 Jul;79(14):9337-40
references.pmid: 15994830
references.citation: Nat Med. 1997 Nov;3(11):1259-65
references.pmid: 9359702
references.citation: AIDS Res Hum Retroviruses. 1996 Jan 20;12(2):83-90
references.pmid: 8834457
references.citation: Clin Infect Dis. 2008 Jul 15;47(2):266-85
references.pmid: 18549313
references.citation: J Acquir Immune Defic Syndr. 2003 Sep 1;34(1):37-44
references.pmid: 14501791
references.citation: J Acquir Immune Defic Syndr. 2000 Jul 1;24(3):218-26
references.pmid: 10969345
references.citation: AIDS. 1999 May 7;13(7):859-60
references.pmid: 10357387
references.citation: Science. 1996 Jul 26;273(5274):415-6
references.pmid: 8677432
references.citation: J Virol. 2003 Dec;77(24):13376-88
references.pmid: 14645592
references.citation: J Virol. 1999 Dec;73(12):10489-502
references.pmid: 10559367
references.citation: J Virol. 2005 Oct;79(19):12296-303
references.pmid: 16160156
references.citation: J Med Virol. 2007 Aug;79(8):1040-6
references.pmid: 17596837
references.citation: BMC Bioinformatics. 2006 Sep 18;7:412
references.pmid: 16978423
references.citation: J Virol. 2007 May;81(10):5413-7
references.pmid: 17329337
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4204-9
references.pmid: 15010526
references.citation: J Virol. 1999 Oct;73(10):8216-26
references.pmid: 10482572
references.citation: J Virol. 2008 Dec;82(23):11758-66
references.pmid: 18815295
references.citation: Virology. 2003 Sep 15;314(1):451-9
references.pmid: 14517097
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12972-7
references.pmid: 14557540
references.citation: J Clin Invest. 2001 Feb;107(4):431-8
references.pmid: 11181642
references.citation: Clin Infect Dis. 2006 Apr 15;42(8):1189-96
references.pmid: 16575741
references.citation: Top HIV Med. 2007 Aug-Sep;15(4):119-25
references.pmid: 17720996
references.citation: J Virol. 2007 May;81(9):4492-500
references.pmid: 17314156
references.citation: Antimicrob Agents Chemother. 2003 Jan;47(1):238-43
references.pmid: 12499197
references.citation: AIDS Res Hum Retroviruses. 2007 Mar;23(3):415-26
references.pmid: 17411375
references.citation: Retrovirology. 2008 May 30;5:43
references.pmid: 18513421
references.citation: Genetics. 2004 Aug;167(4):1573-83
references.pmid: 15342499
references.citation: J Infect Dis. 2008 Mar 1;197(5):714-20
references.pmid: 18260759
references.citation: J Virol. 2005 Aug;79(16):10627-37
references.pmid: 16051855
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3879-84
references.pmid: 18332425