We found that HSV‐2 seropositive women, whether HIV‐seropositive or not, were at greater risk of experiencing BV compared to HSV‐2 seronegative women. To our knowledge, this association between HSV‐2 serostatus and BV occurrence has never been previously reported. Possible explanations are that intermittent HSV‐2 genital shedding in HSV‐2 seropositive women could disrupt vaginal flora, be linked to hormonal changes, or both, which could in turn trigger BV episodes. In support of the former hypothesis, a longitudinal American study assessing the determinants of genital HSV‐2 shedding among HSV‐2 seropositive women found that BV (altered vaginal flora) was strongly associated with HSV‐2 shedding episodes (OR
2.3, 95% CI 1.3 to 4.0).8
In support of the latter, the consistent protective effect of hormonal contraceptive methods on BV occurrence12
and the cyclical occurrence of BV following menstruation, as suggested by a longitudinal study of BV incidence in The Gambia,13
point to a hormonal influence in the occurrence of BV. HSV reactivations could result from a variety of poorly understood stimuli including changes of vaginal pH or menstruation,14
which suggests at least an indirect hormonal influence in triggering HSV and BV episodes. This hypothesis is supported by the association between hormonal contraceptives and HSV‐2 shedding found in the longitudinal American study mentioned above.8
Clearly, further studies are required to investigate the epidemiological and biological relationships between BV and HSV‐2 infection. Importantly, it would be useful to investigate the relative effect of asymptomatic HSV‐2 shedding and/or genital ulcerations on BV occurrence. Unfortunately this could not be performed in this study.
Our data are in accord with previous findings regarding other risk factors for BV. HIV infection has been shown to be a major risk for BV development.2
STIs such as TV and some sexual behaviour indicators have also been associated with BV occurrence,15
although the mechanisms underlying their effect on BV are poorly understood, unless all are markers of a concurrent STI, such as HSV‐2. Vaginal douching has been cited as a possible aetiological factor, but a large study in The Gambia16
did not find any association between vaginal hygiene practices and BV. Similarly, our population reported high levels of vaginal douching but this was not linked to BV occurrence in multivariable analysis. As reported previously, the prevalence of parasitic or bacterial STIs was low in our study population.17
Our study had some limitations. We might have missed some BV episodes that could have occurred between follow‐up visits. Moreover, our results are based on a high‐risk population with specific sexual behaviours, and might not be applicable to general female populations in Africa. However, even if BV incidence was different in general populations, we believe that the likely biological mechanisms underlying the association between HSV‐2 and BV would remain.
- HSV‐2 infection is associated with occurrence of BV episodes, and this association persists whatever the HIV status
- The role of HSV‐2 asymptomatic genital shedding and/or genital ulcerations in the development of BV episodes should be further investigated
- Studies assessing the role of BV on HIV‐1 acquisition should control for HSV‐2 infection in their statistical analyses
When considering together our findings supporting the hypothesis of an association between HSV‐2 and BV and the strong epidemiological link between HSV‐2 and HIV acquisition, it becomes plausible that previous studies reporting an increased risk of acquiring HIV‐1 in women with BV might have been biased by confounding. Indeed, none of the three longitudinal studies3,4,5
that have reported these associations controlled for the presence of HSV‐2 infection. Conversely, it is noteworthy that the large community‐based STI intervention trial performed in Rakai, Uganda, failed to show an association between abnormal bacterial vaginosis and HIV‐1 acquisition,18
despite an initial suggestion of strong associations based on their baseline cross‐sectional study.2
In addition, two trials of presumptive antibiotic prophylaxis to reduce HIV‐1 acquisition showed a marked decrease of BV occurrence without any impact on HIV incidence.19,20
The lack of an association between BV and HIV‐1 incidence was also noted in Burkina Faso, although that study might have had limited statistical power.9
In summary, our findings highlight the need to further investigate the relationships between BV, HSV‐2 and HIV, at the epidemiological level, using appropriate statistical adjustments, and at the biological level to further elucidate the mechanisms of their interactions. This would have important implications for the proper interpretation of studies analysing cofactors of HIV acquisition, including BV.