Cervicovaginal Bacteria May Increase the risk of HIV Acquisition in Women

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UKZN’s Professor Thumbi Ndung’u, renowned HIV scientist, recently published a paper with local colleagues and collaborators from the United States that found a specific bacterial community in the genital tract of healthy South African Durban women that is highly pro-inflammatory; thereby possibly increasing the risk of HIV acquisition.

The ground-breaking study, recently published in the prestigious journal Immunity was conducted on a cohort of HIV negative, 18-23 year old Black South African women enrolled in a study in Durban called FRESH (Females Rising Through Education, Support and Health).

The scientists began assessing the baseline bacterial microbiome in the participants and found that only 37% of participants had Lactobacillus dominant cervicovaginal communities. This is in contrast to published reports of White and Black women in developed countries in which 90% and 62% of women respectively demonstrated Lactobacillus dominance.

Lactobacillus is a type of bacteria with multiple different species in the genus. Most Lactobacillus in humans are considered unharmful and are possibly effective for preventing diarrhoea in children, or a bacterial vaginal infection. Inflammatory reactions in the female genital tract can prevent or eliminate many sexually transmitted infections however the activation of the immune system paradoxically increases the risk that exposure to HIV will lead to infection.

The study found that apart from low-Lactobacillus cervicovaginal communities, the bacterial community structures seen in these young South African women were characterised by a predominance of communities with high ecological diversity. The researchers also measured levels of the immune system signaling molecules called cytokines and found significant individual differences. Cytokine levels among the cervicotypes revealed that the low-Lactobacillus, high-diversity communities were more than four times as likely to have elevated genital inflammatory cytokines.

Previous studies have indicated that seroconversion is associated with raised genital inflammatory cytokines. That is, the risk of HIV acquisition is significantly higher in women with evidence of genital inflammation, defined by at least five of nine inflammatory cytokines being raised.

The study also found that women with the highest levels of cytokine inflammation had active Sexually Transmitted Infections (STI’s). Chlamydia trachomatis was the most prevalent STI in this cohort, with 13% of women testing positive at the first visit. However, the cause of elevated genital inflammation in the majority of women remains unexplained. It was not associated with sexual behaviour, contraceptive usage or demographic characteristics.

The scientists concluded that women with elevated genital inflammation may be three times more likely to become HIV-infected suggesting that generally targeting the genital microbial population may reduce risk. The findings also assist in the development of effective microbicide vaginal gels in HIV prevention for women.

Ndung’u commented on the results, ‘This study provides a clear mechanism for increased genital inflammation in some women, which has been associated with higher risk of HIV infection.  However, it is important to note that the more diverse community with low lactobacillus abundance, may not be necessarily “bad”. Although it is clearly associated with more genital inflammation and possibly increased HIV risk, there may be advantages to this microbiome in South Africa, such as better host defense against genital pathogens that are more specific to this region. Further research will be required to advance this work to interventions but an important finding is that “normal” is geography specific.’ 

Scientists that collaborated with Ndung’u and his UKZN colleagues on this study are from Harvard Medical School, Washington University School of Medicine, Massachusetts General Hospital and the Ragon Institute in the United States.

MaryAnn Francis