title: Vaginal concentrations of lactic acid potently inactivate HIV.
abstract: OBJECTIVE
  When Lactobacillus spp. dominate the vaginal microbiota of women of reproductive age they acidify the vagina to pH <4.0 by producing ∼1% lactic acid in a nearly racemic mixture of d- and l-isomers. We determined the HIV virucidal activity of racemic lactic acid, and its d- and l-isomers, compared with acetic acid and acidity alone (by the addition of HCl).
  
  
  METHODS
  HIV-1 and HIV-2 were transiently treated with acids in the absence or presence of human genital secretions at 37°C for different time intervals, then immediately neutralized and residual infectivity determined in the TZM-bl reporter cell line.
  
  
  RESULTS
  l-lactic acid at 0.3% (w/w) was 17-fold more potent than d-lactic acid in inactivating HIVBa-L. Complete inactivation of different HIV-1 subtypes and HIV-2 was achieved with ≥0.4% (w/w) l-lactic acid. At a typical vaginal pH of 3.8, l-lactic acid at 1% (w/w) more potently and rapidly inactivated HIVBa-L and HIV-1 transmitter/founder strains compared with 1% (w/w) acetic acid and with acidity alone, all adjusted to pH 3.8. A final concentration of 1% (w/w) l-lactic acid maximally inactivated HIVBa-L in the presence of cervicovaginal secretions and seminal plasma. The anti-HIV activity of l-lactic acid was pH dependent, being abrogated at neutral pH, indicating that its virucidal activity is mediated by protonated lactic acid and not the lactate anion.
  
  
  CONCLUSIONS
  l-lactic acid at physiological concentrations demonstrates potent HIV virucidal activity distinct from acidity alone and greater than acetic acid, suggesting a protective role in the sexual transmission of HIV.
authors: Centre for Virology, Burnet Institute, Melbourne, Victoria 3004, Australia. gildat@burnet.edu.au
authors: Muriel
authors: M
authors: Aldunate
authors: David
authors: D
authors: Tyssen
authors: Adam
authors: A
authors: Johnson
authors: Tasnim
authors: T
authors: Zakir
authors: Secondo
authors: S
authors: Sonza
authors: Thomas
authors: T
authors: Moench
authors: Richard
authors: R
authors: Cone
authors: Gilda
authors: G
authors: Tachedjian
mesh_terms: D001826:Body Fluids / Q000821:virology; D005260:Female; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D007778:Lactobacillus / Q000378:metabolism; D050296:Microbial Viability / Q000187:drug effects*; D013696:Temperature; D014621:Vagina / Q000382:microbiology; D038301:Virus Inactivation
chemical_list: D019344:Lactic Acid
keywords: carboxylic acids; female reproductive tract; vaginal lactobacilli; virucidal
references: Curr HIV/AIDS Rep. 2009 Feb;6(1):20-8
references: 19149993
references: J Virol. 2005 Aug;79(16):10247-57
references: 16051818
references: Sex Transm Dis. 2003 Feb;30(2):107-9
references: 12567165
references: J Clin Invest. 2002 Jan;109(2):205-11
references: 11805132
references: J Urol. 1975 Aug;114(2):261-3
references: 240038
references: Ann Clin Microbiol Antimicrob. 2011 Feb 17;10:8
references: 21329492
references: AIDS. 1998 Sep 10;12(13):1699-706
references: 9764791
references: AIDS. 2011 Apr 24;25(7):957-66
references: 21330907
references: Hum Reprod. 2001 Sep;16(9):1809-13
references: 11527880
references: J Infect Dis. 2010 Aug 15;202(3):337-44
references: 20569157
references: Adv Drug Deliv Rev. 2009 Feb 27;61(2):75-85
references: 19135107
references: AIDS. 2010 Jan 16;24(2):163-87
references: 20010071
references: Gynecol Obstet Invest. 1986;21(1):19-25
references: 3485071
references: Mucosal Immunol. 2013 Mar;6(2):427-34
references: 22990624
references: AIDS Res Hum Retroviruses. 2012 Nov;28(11):1485-97
references: 22867060
references: Contraception. 1999 Feb;59(2):91-5
references: 10361623
references: J Exp Med. 1991 Jul 1;174(1):289-92
references: 1647436
references: Sci Transl Med. 2012 May 2;4(132):132ra52
references: 22553250
references: Am J Reprod Immunol. 2012 May;67(5):391-400
references: 22059850
references: Int J STD AIDS. 1995 Jul-Aug;6(4):267-72
references: 7548290
references: Adv Microb Physiol. 1998;39:205-34
references: 9328648
references: J Infect Dis. 2009 May 15;199(10):1506-13
references: 19331578
references: Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):598-603
references: 20018745
references: Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905
references: 12019106
references: J Acquir Immune Defic Syndr. 2006 Dec 1;43(4):499-501
references: 17099316
references: BMC Infect Dis. 2010 May 19;10:120
references: 20482854
references: Sci Transl Med. 2011 Apr 6;3(77):77ra29
references: 21471433
references: J Virol. 2009 Nov;83(21):11196-200
references: 19692470
references: PLoS One. 2010 Aug 23;5(8):e12309
references: 20808791
references: J Clin Microbiol. 1991 Feb;29(2):297-301
references: 1706728
references: J Virol. 2000 Jul;74(13):6087-95
references: 10846092
references: Lancet. 1997 Aug 23;350(9077):546-50
references: 9284776
references: J Acquir Immune Defic Syndr (1988). 1991;4(8):828-30
references: 1856798
references: Sci Transl Med. 2010 Feb 10;2(18):18re1
references: 20371483
references: BMC Infect Dis. 2011 Jul 19;11:200
references: 21771337
references: Appl Environ Microbiol. 2000 May;66(5):2001-5
references: 10788373
references: AIDS. 2008 Jul 31;22(12):1493-501
references: 18614873
references: J Infect Dis. 2005 Jan 1;191(1):25-32
references: 15592999
references: Scand J Infect Dis Suppl. 1983;40:31-5
references: 6582587
references: PLoS One. 2011;6(9):e24095
references: 21935377
references: Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4680-7
references: 20534435
references: J Virol. 1996 May;70(5):3098-107
references: 8627789
references: PLoS Med. 2007 Dec;4(12):e335
references: 18052601
references: J Reprod Fertil. 1973 Apr;33(1):69-75
references: 4699448
references: mBio. 2011 Oct 25;2(6):e00168-11
references: 22027006
references: J Androl. 2005 Jul-Aug;26(4):459-69
references: 15955884
references: J Infect Dis. 2007 Dec 1;196(11):1692-7
references: 18008255
references: AIDS Res Hum Retroviruses. 2012 Jan;28(1):76-81
references: 21595610
references: J Infect Dis. 1985 Aug;152(2):400-3
references: 2993438
references: Infect Immun. 1999 Oct;67(10):5170-5
references: 10496892
references: PLoS Med. 2012;9(6):e1001251
references: 22745608
references: Sex Transm Dis. 2008 Sep;35(9):791-6
references: 18607314
references: Appl Environ Microbiol. 2002 Sep;68(9):4676-8
references: 12200331
references: PLoS One. 2012;7(4):e34540
references: 22509319
references: Proc Natl Acad Sci U S A. 2008 May 27;105(21):7552-7
references: 18490657
references: AIDS Res Hum Retroviruses. 2013 Jan;29(1):13-9
references: 23020644
references: Microbes Infect. 2000 Apr;2(5):543-6
references: 10865199
references: Biochem Cell Biol. 2003 Feb;81(1):1-7
references: 12683630
references: Obstet Gynecol. 2011 Oct;118(4):840-6
references: 21934447
references: Cochrane Database Syst Rev. 2009 Oct 07;(4):CD006289
references: 19821358
references: J Virol. 2001 Nov;75(21):10073-89
references: 11581376
references: Annu Rev Med. 2011;62:127-39
references: 21054171
references: AIDS Res Hum Retroviruses. 1990 Dec;6(12):1433-6
references: 2078421
references: PLoS One. 2012;7(5):e36934
references: 22655031
references: J Exp Med. 2009 Jun 8;206(6):1273-89
references: 19487424
references: Clin Microbiol Infect. 2007 Jul;13(7):657-64
references: 17633390
references: Br J Obstet Gynaecol. 1985 Dec;92(12):1267-71
references: 3910080
references: FEMS Immunol Med Microbiol. 2011 Mar;61(2):153-8
references: 21118312
references: J Obstet Gynaecol Res. 2006 Apr;32(2):243-51
references: 16594932
references: J Parasitol. 1992 Feb;78(1):157-60
references: 1310732
references: Rev Assoc Med Bras (1992). 2011 Jul-Aug;57(4):415-20
references: 21876923
references: BMC Infect Dis. 2005 Sep 30;5:79
references: 16194280
references: Fertil Steril. 1971 Jan;22(1):64-8
references: 5538756
references: Sex Transm Dis. 2011 Nov;38(11):1040-5
references: 21992981