Vaginal concentrations of lactic acid potently inactivate HIV

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). HIV-1 and HIV-2 were transiently treated with acids in the absence or presence of human genital secretions at 37C for different time intervals, then immediately neutralized and residual infectivity determined in the TZM-bl reporter cell line. 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. 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.