Bacterial vaginosis causes changes in the immune system in the genital tract of women with HIV

Bacterial vaginosis causes local changes in the cervix of HIV-positive women that are reversible with appropriate antibiotic treatment, investigators report in the December 15^th edition of the Journal of Acquired Immune Deficiency Syndromes. The study’s investigators believe that their findings provide a rationale for examination of the restoration of vaginal flora as a way of reducing HIV transmission.

The immune environment in the female genital tract is important to the risk of HIV acquisition and transmission. Bacterial vaginosis involves an alteration of the normal bacterial flora in the female genital tract. Increased genital shedding of HIV has been observed in HIV-positive women with bacterial vaginosis.

Authors of a recent meta-analysis of the role of bacterial vaginosis on the shedding of HIV in the genital tract called for more research into this subject.

An international team of investigators hypothesised that the increase in genital HIV shedding was because bacterial vaginosis caused changes in the genital immune cell population, most importantly an increase in CD4 cells with the CCR5 co-receptor, which are targets for infection with the virus and could increase local HIV replication.

They therefore examined the immune cells present in 15 HIV-positive Kenyan sex workers, all of whom had bacterial vaginosis. Cervical samples were obtained before and after the women received antibiotic treatment for bacterial vaginosis with metronidazole.

None of the women had bacterial sexually transmitted infections, but all were infected with herpes simplex virus-2 (HSV-2). However, none had any evidence of genital ulceration during the study.

Antiretroviral therapy was being taken by eight women and six of these had an undetectable viral load in their blood. The patients taking anti-HIV drugs had a median CD4 cell count of 274 cells/mm³.

Median blood viral load in the women not taking HIV treatment was 1137 copies/ml. Only one woman had a viral load above 5000 copies/ml. Median CD4 cell count was a little under 500 cells/mm³.

Cervical samples collected before antibiotic treatment had a median Nugent score of 8.1 (a score above 7 is defined as bacterial vaginosis). This fell significantly with antibiotic treatment to a median score of 4.5 (p

Shedding of HSV-2 was detected in one patient before antibiotic treatment and in one patient after such treatment.

Genital shedding of HIV was only detected in one woman before metronidazole treatment. This was a patient with a blood viral load above 5000 copies/ml. After antibiotic treatment, none of the women shed HIV in their genital secretions.

Treatment for bacterial vaginosis was associated with significant changes in the immune environment in the cervix. Of particular note, there was a marked decline in the number of CD4 cells (2.17 log₁₀pg/ml before treatment, 1.69 log₁₀ pg/ml after treatment, p 10 pg/ml vs. 1.35 log₁₀ pg/ml, p = 0.003). Furthermore, antibiotic treatment achieved a significant fall in levels of genital proinflammatory cytokines, including interleukin 1b (2.4 log₁₀ pg/ml vs. 1.7 log₁₀ pg/ml, p = 0.03).

“We have confirmed that bacterial vaginosis in HIV-infected women was associated with reversible increases in genital levels of proinflammatory cytokines. In addition, for the first time to our knowledge, we define reversible increases in activated CD4+ T cells in the genital mucosa”, comment the investigators.

They acknowledge, however, that the findings of their study are limited by its small size and by the fact that the majority of women were taking antiretroviral therapy.

Nevertheless, they conclude that their study shows that “bacterial vaginosis has a substantial impact on mucosal immune cell populations in the female genital tract. We postulate that these changes may underpin both the association of bacterial vaginosis with increased proinflammatory cytokine levels and the association of bacterial vaginosis with increased genital levels of HIV.”

The investigators add, “this provides further rationale for the study of vaginal flora restoration as a potential strategy to reduce the sexual transmission of HIV.”