In this large cohort of HIV infected and uninfected women, we found that vitamin D deficiency was very common and independently associated with BV among HIV-infected women; 59% of women studied had vitamin D deficiency, and an additional 24% had insufficient levels of vitamin D.
HIV-infected women deficient in vitamin D were more than three times as likely by multivariable analysis to have BV compared to HIV-infected women with sufficient vitamin D levels. In HIV-uninfected women, we found no association between vitamin D deficiency and BV, although the number of observations was relatively small. The mechanism by which vitamin D deficiency may increase susceptibility to BV is not clear. The classic infections associated with vitamin D deficiency are mycobacterial diseases.17
The mechanism underlying this association is thought to be the role of vitamin D in regulating the production and function of innate antimicrobial defense molecules, such as cathelicidin, a neutrophil degradation product found in the female genital tract.18
Cathelidicin has antibacterial properties and may influence susceptibility to intracellular as well as extracellular pathogens; the molecule is found in granules in the neutrophils that are destined for exocytosis.19
Vitamin D receptors are found in many human tissues and have been found to be an important regulator of host immune response to bacterial infections, such as dental infections and lower respiratory tract infections.20
Vitamin D is also linked to cytokine expression in a number of disease states and in vitro
In HIV infection specifically, our understanding of the effect of vitamin D on immune function is rapidly evolving but far from clear.22
Vitamin D deficiency was associated with lower CD4 count in one study of postmenopausal women,23
but other studies have not confirmed the association.24,25
Women with HIV were less likely to have BV, but among HIV-infected women, those with a lower CD4 count were more likely to have BV. These apparently contradictory findings are explained, we believe, by two separate phenomena. Women with HIV are more likely to be sexually abstinent and when they do have intercourse, are more likely to use condoms.26
However, HIV infection, particularly immunosuppression defined by a CD4 count <200, is associated with more persistent infection once BV occurs.11
This study is one of several reporting an association between BV and specific nutritional deficiencies or nutritional status. The current study and all such studies need to be interpreted with the recognition that nutritional deficiencies rarely occur in isolation and are often a reflection of poor health status overall, which in turn may reflect poverty and other social or economic adversity. BV has been found to be associated with iron deficiency among pregnant women,27
lower concentrations of vitamins A, C, E, and beta carotene among HIV-infected and uninfected women in the HIV Epidemiology Research Study (HERS) study,28
higher intake of dietary fat and lower intake of vitamin E, folate, and protein among nonpregnant women,29
and lower BMI in a cohort of nonpregnant women in India.30
We did not have diet history or levels of other nutrients available to aid in the interpretation of our data from the WIHS participants.
Vitamin D deficiency may partially explain the higher rates of BV observed in black women compared to white women. Racial discrepancies in the prevalence of BV have long been observed but are not fully explained and have been found to be independent of markers of SES, sexual practices, and other behaviors, such as smoking and douching.31
Several biologic differences between black and white women may be relevant to this racial disparity. Differences in genital cytokine expression have been found between black and white pregnant women with normal flora,32
and differences in coordinated regulation of the local genital immune response have also been reported.33
BV prevalence and incidence has been found to be associated with higher chronic stress levels,34
and there may be genetic differences across ethnicities in stress-related genes that affect BV prevalence.35
Whether there is a relationship between vitamin D deficiency and these racial differences in immune response is unclear and requires further mechanistic study.
This is a cross-sectional study; confirmation of these findings will require larger longitudinal epidemiologic studies. BV in our study was defined by the Amsel criteria, which is not the gold standard diagnostic test. When compared against the gold standard Nugent gram stain, Amsel criteria are found to be 36%–70% sensitive and 94%–98% specific, with the lower sensitivity reported in a previous study in the WIHS.36,37
Because of the specificity of the Amsel criteria, we are confident that the vast majority of cases are true cases. However, the lack of sensitivity implies that cases of BV were missed and could have biased our analysis; thus, our findings should be considered preliminary. For the women participating in the metabolic substudy, vitamin D measurements were performed in the context of a substudy looking at bone health. The inclusion criteria for this study (lack of diabetes, corticosteroids, or bisphosphonates medications) would not be expected to alter the relationship between BV and vitamin D deficiency. Because the population was not chosen randomly, however, there may be unanticipated effects for which we have not controlled.