Vaginal concentrations of lactic acid potently inactivate HIV

Abstract

ObjectivesWhen 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).MethodsHIV-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.Resultsl-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.Conclusionsl-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.

Distinct Mechanisms Regulate Exposure of Neutralizing Epitopes in the V2 and V3 Loops of HIV-1 Envelope

“…Virus infectivity decreased to Ͻ10% at pH 4.2 and 5.6 but remained unchanged at pH 6.6 compared to the infectivity at pH 7.4. In agreement with these data, past studies demonstrate that the acidic pH of Ͻ5.0 in the vaginal mucosa is detrimental to the virus but that semen neutralizes the environment, promoting virus transmission (62)(63)(64). At pH 6.6 and pH 7.4, the levels of virus neutralization by V2i MAb 2158 were comparable whether the virus was incubated with the MAb for 1 h or 5 h. Hence, unlike incubation time, pH and temperature in the limited ranges tested have minimal effects on virus neutralization by V2i MAbs.…”

Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV/STI prevalence and genital HIV viral load in African women

“…L. crispatus is an efficient lactic acid producer (Hickey et al, 2012), produces antimicrobial compounds (Graver and Wade, 2011;Hickey et al, 2012;Aldunate et al, 2013;Petrova et al, 2013) and inhibits inflammation (Rose et al, 2012;Petrova et al, 2013). The latter is particularly important in the context of HIV transmission, as HIV infects CD4 þ -immune cells that are recruited to the genital mucosa when inflammation is present.…”

Role of Semen in Modulating the Female Genital Tract Microenvironment – Implications for HIV Transmission

“…61,62 The buffering capacity of semen may help to maintain conditions that are conducive to HIV-1 stability and infection. [63][64][65][66] 72 Furthermore, complement activation in seminal fluid generates C3 cleavage and augments HIV-1 infection in epithelial cells. 73 In vaginal epithelial cells, SP induces the secretion of CCL20 and subsequent recruitment of LCs.…”