title: Use of a high resolution melting (HRM) assay to compare gag, pol, and env diversity in adults with different stages of HIV infection.
abstract: BACKGROUND
  Cross-sectional assessment of HIV incidence relies on laboratory methods to discriminate between recent and non-recent HIV infection. Because HIV diversifies over time in infected individuals, HIV diversity may serve as a biomarker for assessing HIV incidence. We used a high resolution melting (HRM) diversity assay to compare HIV diversity in adults with different stages of HIV infection. This assay provides a single numeric HRM score that reflects the level of genetic diversity of HIV in a sample from an infected individual.
  
  
  METHODS
  HIV diversity was measured in 203 adults: 20 with acute HIV infection (RNA positive, antibody negative), 116 with recent HIV infection (tested a median of 189 days after a previous negative HIV test, range 14-540 days), and 67 with non-recent HIV infection (HIV infected >2 years). HRM scores were generated for two regions in gag, one region in pol, and three regions in env.
  
  
  RESULTS
  Median HRM scores were higher in non-recent infection than in recent infection for all six regions tested. In multivariate models, higher HRM scores in three of the six regions were independently associated with non-recent HIV infection.
  
  
  CONCLUSIONS
  The HRM diversity assay provides a simple, scalable method for measuring HIV diversity. HRM scores, which reflect the genetic diversity in a viral population, may be useful biomarkers for evaluation of HIV incidence, particularly if multiple regions of the HIV genome are examined.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Cousins
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Geetha
authors.initials: G
authors.lastname: Beauchamp
authors.forename: Ronald
authors.initials: R
authors.lastname: Brookmeyer
authors.forename: William I
authors.initials: WI
authors.lastname: Towler
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hudelson
authors.forename: Leila
authors.initials: L
authors.lastname: Khaki
authors.forename: Beryl
authors.initials: B
authors.lastname: Koblin
authors.forename: Margaret
authors.initials: M
authors.lastname: Chesney
authors.forename: Richard D
authors.initials: RD
authors.lastname: Moore
authors.forename: Gabor D
authors.initials: GD
authors.lastname: Kelen
authors.forename: Thomas
authors.initials: T
authors.lastname: Coates
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Susan P
authors.initials: SP
authors.lastname: Buchbinder
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
mesh_terms: D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D015752:Genes, env; D015750:Genes, gag; D015751:Genes, pol; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers
references.citation: J Acquir Immune Defic Syndr Hum Retrovirol. 1998;17 Suppl 1:S38-41
references.pmid: 9586651
references.citation: AIDS Rev. 2010 Apr-Jun;12(2):89-102
references.pmid: 20571603
references.citation: AIDS. 2010 Nov 27;24(18):2763-71
references.pmid: 20975514
references.citation: Clin Chem. 2004 Oct;50(10):1748-54
references.pmid: 15308590
references.citation: AIDS Res Hum Retroviruses. 2010 Aug;26(8):913-8
references.pmid: 20666583
references.citation: Expert Rev Mol Diagn. 2010 Mar;10(2):219-40
references.pmid: 20214540
references.citation: J Acquir Immune Defic Syndr. 2009 Sep 1;52(1):121-4
references.pmid: 19506484
references.citation: Lancet. 2004 Jul 3-9;364(9428):41-50
references.pmid: 15234855
references.citation: J HIV AIDS Surveill Epidemiol. 2010 Jan 1;2(1):1-14
references.pmid: 21743821
references.citation: J Virol. 1999 Dec;73(12):10489-502
references.pmid: 10559367
references.citation: AIDS Res Hum Retroviruses. 2003 Jul;19(7):625-9
references.pmid: 12921095
references.citation: Lancet Infect Dis. 2009 Dec;9(12):747-59
references.pmid: 19926035
references.citation: AIDS Rev. 2007 Apr-Jun;9(2):75-87
references.pmid: 17694675
references.citation: Curr Infect Dis Rep. 2007 Mar;9(2):161-6
references.pmid: 17324354
references.citation: J Clin Microbiol. 2000 Feb;38(2):773-80
references.pmid: 10655384
references.citation: AIDS. 2009 Mar 13;23(5):579-87
references.pmid: 19516110
references.citation: J Virol. 2010 Jun;84(12):6241-7
references.pmid: 20375173
references.citation: Trans Am Clin Climatol Assoc. 2004;115:289-303
references.pmid: 17060974
references.citation: AIDS. 2003 Sep 5;17(13):1871-9
references.pmid: 12960819
references.citation: Nat Med. 2000 Jan;6(1):71-5
references.pmid: 10613827
references.citation: Clin Infect Dis. 2011 Feb 15;52(4):532-9
references.pmid: 21220770
references.citation: AIDS Res Hum Retroviruses. 2007 May;23(5):667-74
references.pmid: 17530991
references.citation: J Virol. 2002 Dec;76(23):11953-9
references.pmid: 12414937
references.citation: Epidemiol Rev. 2010;32:26-37
references.pmid: 20203104
references.citation: J Infect Dis. 2001 Jan 1;183(1):23-35
references.pmid: 11106536
references.citation: J Virol. 1997 Oct;71(10):7498-508
references.pmid: 9311829
references.citation: J Clin Microbiol. 2004 Jun;42(6):2623-8
references.pmid: 15184443
references.citation: AIDS. 2008 Feb 19;22(4):497-501
references.pmid: 18301062
references.citation: J Acquir Immune Defic Syndr. 2008 Jun 1;48(2):211-5
references.pmid: 18520680
references.citation: Curr Opin HIV AIDS. 2010 Jul;5(4):327-34
references.pmid: 20543609
references.citation: Proc Natl Acad Sci U S A. 2008 May 27;105(21):7552-7
references.pmid: 18490657
references.citation: AIDS. 2002 Jan 4;16(1):113-9
references.pmid: 11741169
references.citation: PLoS Pathog. 2010 May 13;6(5):e1000890
references.pmid: 20485520
references.citation: Euro Surveill. 2008 Sep 04;13(36):
references.pmid: 18775293
references.citation: Arch Virol. 2008;153(7):1233-40
references.pmid: 18504522
references.citation: PLoS One. 2011 Apr 14;6(4):e18642
references.pmid: 21533179