Common vaginal infection may double HIV acquisition risk

Bacterial vaginosis (BV), the most common vaginal infection in women of childbearing age, may double a woman's susceptibility to HIV infection, according to the results of a South African study published in the October 15^th edition of The Journal of Infectious Diseases which is now available online. If more effective diagnosis and treatment were available, argues an accompanying editorial, HIV infection rates in the developing world could be substantially reduced.

Bacterial vaginosis (BV) is a condition in women where the normal balance of bacteria in the vagina is disrupted, resulting in a change from an acidic to an alkaline environment. Although it is sometimes accompanied by symptoms such as discharge, odour, pain, itching, or burning, it is often asymptomatic. Although no pathogen has been isolated as the cause, it is considered to be a sexually transmitted infection (STI), and, since it affects between 20%-25% of the general population, and up to 50% of women attending sexual health clinics, it is the most common STI worldwide. BV has been implicated in premature delivery in pregnant women and in the development of pelvic inflammatory disease.

Several - but not all - epidemiological and prospective studies have found an association between BV and HIV infection. In addition, in vitro studies suggest that BV has the potential to increase susceptibility to HIV infection, possibly through increased production of interleukin (IL)-10 and/or increased secretion of tumour necrosis factor-alpha (TNF-α) and IL-1ß.

Given the high prevalence of BV and HIV in many parts of sub-Saharan Africa, identifying and treating BV could have significant implications for HIV prevention. Consequently, investigators at the University of Cape Town, South Africa, sought to ascertain whether there was indeed an association between BV and HIV acquisition.

They conducted a case-control study, nested within a randomised controlled trial evaluating cervical cancer screening in Khayelitsha, near Cape Town. Of the 5110 women who were HIV-negative at enrolment (between June 2000 and December 2002), the investigators selected all women who had seroconverted by December 2003 (n=86; overall incidence rate, 2.1/100 person-years) for this study. The majority of seroconversions (64%) were identified at the 6-month follow-up visit, although the investigators report that risk of seroconversion remained constant throughout the 36-month follow-up period (data not shown).

A further 324 age-matched women were selected at random from the cohort as controls.

Women who seroconverted were significantly more likely to be unmarried, to report having had more than one sex partner in the month before enrolment, and to report having a new sex partner at the 6-month follow-up visit.

BV was assessed only once, during the enrolment visit, by gynaecological examination (Amsel criteria). Blinded microbiologic assessment (Nugent scoring) of Gram-stained slides also assessed BV status.

Using Amsel criteria, only 20% of the HIV-positive women were found to have BV, compared with 16% of the controls. However, using Nugent scoring, 74% of the seroconverters with suitable samples (n=59) had a BV diagnosis (Nugent scores between 7-10) compared with 62% of controls (n=189). Compared to the women with normal vaginal flora, the women who seroconverted were significantly more likely to have BV, as diagnosed by Nugent scoring (summary odds ratio [OR], 1.83; 95% CI, 1.00-3.85).

In multivariate analysis, after adjusting for demographic characteristics, other STIs and sexual behaviours, women with BV diagnosed by Nugent scoring were significantly more likely to seroconvert than women with normal vaginal flora (adjusted OR, 2.01; 95% CI, 1.12-3.62).

The investigators point out several limitations to their study, including the fact that BV was assessed only once and HIV seroconversions were identified over three years. During this time, vaginal flora may have changed, and a baseline BV assessment may not accurately reflect presence of BV at the time of seroconversion. The investigators also did not assess the presence of ulcerative STIs, including herpes simplex virus 2 (HSV-2), which have been found to increase HIV acquisition risk. It is also possible that other unknown confounding measures may have inflated the association between BV and HIV acquisition.

However, they conclude "if BV increases women's susceptibly to HIV infection, interventions to reduce the occurrence of BV may have an impact on the spread of HIV at a population level. The high prevalence of BV in our study population means that almost one-third of all new HIV infections in women in this setting might be prevented if all cases of BV could be cured".

Nevertheless, an accompanying editorial by Dr Jane Schwebke of the University of Alabama at Birmingham points out that "present achievable BV cure rates, combined with high recurrence rates make this solution impracticable."

Although many of the women in the study (27% of seroconverters and 23% of controls) were treated for BV with the antibiotic metronidazole, this made no difference to HIV seroconversion rates. Indeed, a recent study from Kenya found that antibiotic prophylaxis failed to reduce HIV seroconversions .

In order to make a difference, more research into the cause, diagnosis and treatment of BV is urgently required, argues Dr Schwebke. "Until efficacious therapy, as well as an understanding of prevention methods, for BV is available," she concludes, "it will not be feasible to go forward with studies aimed at preventing the complications of this common vaginal infection."