Role of vaginal flora in the transmission of HIV and other STIs

Role of vaginal flora in the transmission of HIV and other STIs

Project

Everybody caries bacteria essential for the human body to function properly. AMC researcher, Janneke van de Wijgert, is trying to identify a correlation between the disruption to vaginal flora and the transmission of HIV and other STIs. The hypothesis assumes that the prevalence of HIV transmission between men and women is due to a disruption in the composition of the vaginal flora and related inflammation.

Project details

Time frame
13 December 2011 - 24 March 2016
Budget
€ 248,693
Active in
Netherlands

Objectives

This project aims to investigate the interactions between the vaginal microbiome and HIV
Research questions:
1. Do the composition(s) of the vaginal microbiome of women who subsequently seroconverted for HIV differ from those of women who remained HIV-negative? [Specimens from KHIS seroconverters]
2. Is the level of genital HIV shedding by HIV-positive women associated with specific composition(s) of the vaginal microbiome? [Specimens from HIV-positive women enrolled in the Biomarkers study].
3. Which vaginal microbiome compositions are associated with cervicovaginal inflammatory responses that are likely to make a woman more vulnerable to HIV acquisition or transmission? [Specimens from the two African cohort studies].
4. Are these vaginal microbiome compositions also commonly found in Dutch women? [Specimens from the HELIUS cohort].
5. How do HPV and HSV-2 infections - which are both associated with increased HIV influence the vaginal microbiome?
6. How do acute STIs influence the vaginal microbiome and cervicovaginal cytokine profiles? [Women with laboratory-confirmed acute STIs from the two African cohort studies and STI-negative controls].

Normalizing the vaginal microbiome may be an effective strategy for reducing HIV, HPV, and HSV-2 acquisition and transmission, but only if we succeed in normalizing it for extended periods of time. Interventions so far have shown disappointing results, mostly due to our limited understanding of the imbalanced vaginal microbiome and associated inflammatory responses [9]. An increased understanding would significantly improve our ability to target interventions and study their biological effects.

Community groups

scientific community

Background

Much remains to be discovered about the role of the human microbiome in health and disease. Based on epidemiological studies conducted by us and others, we hypothesize that a substantial proportion of HIV transmissions between women and men occur because of imbalanced compositions of the vaginal microbiome and associated cervicovaginal inflammation. Such imbalances are extremely common, affecting about one third of women worldwide. Interactions between the vaginal microbiome, HIV and other sexually transmitted infections (STI), and cervicovaginal inflammation, are poorly understood.

The etiology and consequences of an imbalanced vaginal microbiome are not yet well understood. The causative micro-organisms can be transmitted between sexual partners, but can also migrate from the gut to the urogenital tract [1]. Four prospective cohort studies have shown significant associations between BV by Amsel or Nugent criteria and subsequent acquisition of HIV in women, with hazard ratios ranging from 1.4 to 2.3 [reviewed in 2]. Similar association have been found between vaginal candidiasis and HIV acquisition [2]. This suggests that any deviation from a normal lactobacilli-dominated vaginal microbiome increases women’s susceptibility to HIV. This relationship appears to be bidirectional: women who are already HIV-infected and have an imbalanced vaginal microbiome are more likely to have an increased HIV viral load in their genital tract, even when their plasma viral load is suppressed by cART [6,7]. They are therefore more likely to transmit HIV to their sexual partners. More recently, bidirectional relationships between BV by Amsel or Nugent criteria and other viral STIs (HPV and HSV-2) have also become apparent, and these viral STIs in turn are known to be associated with HIV acquisition and onward transmission [2]. Many details of these relationships have not been adequately elucidated. It is likely – but not proven – that BV-associated bacteria (and STI co-infections) cause inflammatory processes in the cervicovaginal mucosa, including the recruitment of activated immune cells that are target cells for HIV [8]. It is not yet known, however, which bacteria cause which inflammatory responses, how long these inflammatory responses persist after removal of the causative organism(s), and what the relationships are between other STIs and the vaginal microbiome.

Goals

< 200,000 new HIV infections globally
50%
Contributed within this project
Radical reduction in the Big Six STIs and 0 new HIV infections
50%
Contributed within this project

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