Stay it with flora: maintaining vaginal health as a possible avenue for prevention of human immunodeficiency virus acquisition.

As is the case for all anatomic sites with a mucosal surface, the vagina may be colonized by a variety of bacteria, fungi, and other potential pathogens. A normal vaginal flora is predominately composed of Lactobacillus species, with low bacterial diversity [1]. Lactobacilli provide significant health benefits to the host by decreasing the vaginal pH through lactic acid production, generating H2O2 and bacteriocins, and stimulating the local immune system [2], all of which serve as barriers to pathogens. Thus, an abnormal vaginal flora may have significant implications for the transmission of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). It is therefore unfortunate that, in the real world, a normal (i.e., lactobacilli-predominant) vaginal flora is not the norm. The bacterial composition of the vaginal flora within a population constitutes a spectrum. In some individuals, H2O2producing Lactobacillus species predominate, whereas in others, the flora may include an increasing proportion of various bacterial species, such as Gardnerella vaginalis, Mycoplasma hominis, and gramnegative and gram-positive anaerobes, including Prevotella organisms [1, 3]. This spectrum is often quantified numerically by means of the Nugent scoring system, with flora classified as “normal,” “intermediate,” or “bacterial vaginosis” [4]. On the basis of this system, the vaginal flora is actually abnormal (i.e., it is classified as intermediate or bacterial vaginosis) in at least half of women. This abnormal status tends to recur frequently and rapidly in women who have received BV therapy [2]. The prevalence of abnormal vaginal flora is particularly high among women from subSaharan Africa [5, 6], where several studies found an association between BV and HIV acquisition [2, 5–7] and where the prevalence of HIV infection is also disproportionately high among women—particularly young women [8]. Of importance, a less abnormal flora may also increase HIV susceptibility, because there is a linear association between the Nugent score and the probability of HIV acquisition [5–7]. Other causes of vaginitis, including infection by Candida albicans and Trichomonas vaginalis, are also common and can cause significant symptoms, with T. vaginalis infection most consistently linked to HIV acquisition [9, 10]. There are several mechanisms by which alterations in vaginal flora and other causes of vaginitis might enhance HIV acquisition. Loss of a lactobacillipredominant flora is associated with an increased vaginal pH, an absence of H2O2, and a reduction in mucosal levels of secretory leukocyte protease inhibitor, an innate immune factor with anti-HIV activity [2, 11]. Both bacterial vaginosis and intermediate flora have also been associated with substantial local increases in proinflammatory cytokine levels, as have other vaginal infections [12, 13]. These cytokines might directly enhance HIV replication, but because they are produced by activated immune cells, including CD4 T cells and monocytes/dendritic cells, they are perhaps more importantly a marker for increased numbers of HIV-susceptible target cells in the genital mucosa [14, 15]. Finally, BV may enhance acquisition of herpes simplex virus type 2 (HSV-2), a major cofactor in both the acquisition and secondary transmission of HIV [16], and BV may also increase susceptibility to other STIs, such as T. vaginalis infection, Neisseria gonorrhoeae infection, and Chlamydia trachomatis infection [17–19]. Received 6 January 2008; accepted 8 January 2008; electronically published 9 April 2008. Potential conflicts of interest: none reported. Financial support: Canadian Research Chair Programme (salary support to R.K.), Canadian Institutes of Health Research (studentship to L.Y.S.), and Ontario HIV Treatment Network (grant ROGB194). Reprints or correspondence: Dr. Rupert Kaul, Clinical Science Div., University of Toronto, Medical Sciences Bldg. #6356, Toronto, Ontario, Canada, M5S 1A8 ([email protected]). The Journal of Infectious Diseases 2008; 197:1355–7 © 2008 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19710-0001$15.00 DOI: 10.1086/587491 E D I T O R I A L C O M M E N T A R Y