Boosting vaginal health could cut HIV risk

Oral treatment to improve vaginal health could have the potential to reduce the risk of infection with HIV for women, according to a study published in the May 15^th edition of Clinical Infectious Diseases.

Most new HIV infections in sub-Saharan Africa are among women, for whom new HIV-prevention strategies are needed. Disturbances of vaginal flora may substantially contribute to HIV acquisition, so researchers have been studying simple, safe, and inexpensive interventions to reduce the rate of vaginal infections and promote normal vaginal flora such as lactobacilli.

A previous study found that twice weekly administration of the antibiotic metronidazole into the vagina was effective against the abnormal flora known as bacterial vaginosis (BV). Now, a team from the US and Kenya report a similarly effective regime using directly observed oral therapy.

The prevalence of abnormal vaginal flora is particularly high among women from sub-Saharan Africa, where several studies found an association between BV and HIV acquisition and where the prevalence of HIV infection is also particularly high among young women, explain commentators Lucy Shin (University of Toronto, Canada) and colleague Rupert Kaul.

A less abnormal flora may also increase HIV susceptibility, and other causes of vaginitis, such as the sexually transmitted infection (STI) trichomoniasis, might also enhance HIV acquisition.

R Scott McLelland (University of Washington, Seattle, USA) conducted a randomised trial of monthly oral therapy to reduce vaginal infections among female Kenyan sex workers at risk of HIV. Treatment with 2g metronidazole plus 150mg fluconazole was compared with placebos. The primary end points were BV, vaginal candidiasis, trichomoniasis, and the presence of lactobacilli.

The investigators obtained demographic information and took detailed medical and sexual histories. They then performed physical examinations and collected vaginal and cervical specimens and blood HIV testing. Similar follow-ups were done each month, when study drugs or placebo were administered as directly observed therapy. All participants received monthly risk-reduction counselling and free condoms.

A total of 310 women were enrolled in the study between May 2003 and November 2005, and equally randomised into the two study arms. Median follow-up was twelve months and 303 women completed the study.

Participants in the two study arms were similar in baseline characteristics, and laboratory findings revealed that 40% had vaginal infections.

During follow up, women receiving the antibiotics had almost half the episodes of BV (hazard ratio [HR] 0.55; 95% CI 0.49–0.63, p Lactobacillus species (HR 1.47; 95% CI 1.19 –1.80, p

The incidence of vaginal candidiasis and trichomoniasis amongst the women treated with antibiotics were lower than those seen in the placebo arm, but the differences were not statistically significant. Five women in the treatment arm and seven in the placebo arm were infected with HIV (HR 0.6; 95% CI, 0.2–2.3; p = 0.6). Six women in each study arm acquired gonorrhoea.

“This trial demonstrated that periodic presumptive treatment with oral metronidazole and fluconazole reduced BV incidence and increased vaginal colonization with Lactobacillus organisms,” the authors write.

Since it seems likely that these findings may be generalisable to other African women, the authors conclude that “vaginal health interventions have the potential to provide simple, female-controlled approaches for reducing the risk of HIV-1 acquisition”. However, given the limited success of the trial intervention, “approaches that have a greater impact on vaginal infections are needed to maximize the potential usefulness of vaginal health interventions for reducing the risk of HIV-1 acquisition”.

Although efforts to control HIV by means of population-based measures that target classic STIs have had limited success, the authors of an accompanying editorial suggest that “the prevention of vaginitis might be a more effective strategy to block HIV transmission in sub-Saharan Africa, because vaginitis is much more common than STIs among women in the general population”. However, the possibility exists that the association of vaginitis with HIV acquisition may be driven at least in part by coinfections, such as HSV-2, that will not be prevented by therapy used in this trial.

So far, studies investigating HSV-2 suppression as a form of HIV prevention have not been successful. The authors of the editorial conclude that “the formal demonstration that vaginal flora–focused interventions can prevent HIV will require a complex, costly, and time-consuming clinical trial, but the need for such female-focused prevention strategies has never been greater.”