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FGT microbiome

Susceptibility of heterosexual sub-Saharan women to HIV could be the result of cervicovaginal microbiome characteristics

30 Jan, 17 | by Leslie Goode, Blogmaster

Could part of the explanation for the apparent susceptibility of sub-Saharan African heterosexual women to HIV infection (eight-fold that of males) lie in the bacterial flora of their female genital tract (FGT)?

Studies published in STI journal have considered the relationship between a certain state of the FGT bacterial microbiome – especially the depletion of lactobacillus (Francis & Grosskurth/STIs) – and the susceptibility to BV (Antonio & Hillier/STIs; Hardy & Crucitti/STIs; Francis & Grosskurth/STIs; Haggerty & Ness/STIs), to pelvic inflammatory disease (Haggerty & Ness/STIs), and to other STIs (Francis & Grosskurth/STIs).  Others have observed the prevalence of Lactobacillus in the healthy FGT microbiome (Madhivanan & Krupp/STIs), and considered the impact on the FGT lining of practices of vaginal douching (Balkus & McClelland/STIs), hormonal contraception (Verwijs & Wijgert/STIs), and sexual debut (Jespers & Crucitti/STIs).

Highly relevant to all these discussions is a recently published study by Gosmann & Anahtar of a prospective cohort of 236 young HIV-negative women participating in the South African Ragon Institute’s FRESH study (Females Rising through Educations, Support and Health) in Kwa-Zulu Natal. The researchers were able to follow up their cohort for a total of 198.2 person-years, in the course of which 31 participants acquired HIV.  The researchers distinguish four ‘cervicotypes’ in respect to FGT bacterial flora; then determine their prevalence along with their association with ‘HIV target cells’ (i.e. activated CD4 T cells expressing the HIV co-receptor CCR5) and HIV acquisition.

The four cervicotypes correspond to the dominance of Lactobacillus crispatus and of Lactobacillus iners (CT1 and CT2, respectively), the preponderance of Gardnerella vaginalis (CT3), and a biome showing a far more diverse range of bacterial types (CT4).  Strikingly, the first two cervicotypes (CT1 and CT2) account for only 10% and 32% of women in the cohort; while, among white women in Western countries, the proportion showing Lactobacillus dominance would be c.90%.  The other 58% fall into the categories of high diversity communities with low Lactobacillus abundance (CT3 and CT4).  More interestingly still, none of the 31 HIV sero-conversions took place among the 10% of women with CT1-type bacterial flora.  Rather, sero-conversions were fairly evenly distributed among the other three cervicotypes, with some diminution of relative incidence in the CT2 category (i.e. nine sero-conversions, as opposed to 10 and 12 in CT3 and CT4 respectively).  Researchers observed a 17-fold increase in HIV target cells in women with a CT4-type cervico-vaginal microbiome as against those with CT1-type, and elevated levels of chemokines MIP-α and MIP-β which attract CCR5 expressing cells in women with diverse FGT bacterial communities.

Sadly, regimens aiming to restore Lactobacillus crispatus dominance (e.g. antibiotics or probiotic vaginal suppositories) show significant recurrence rates.  However, modifiable biological and behavioural factors may play a considerable role on Lactobacillus depletion in sub-Saharan African women (e.g. vaginal washing; antibiotic use; recent Trichomonas and HSV-2).  If so, then, as Baeten & McClelland/STIs point out, this would suggest the possibility of effective intervention strategies to reduce HIV transmission by improving vaginal health.

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