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Dr
Anna-Ursula Happel

South Africa

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Project Title

Interaction of vaginal virome and bacteriome in pregnant women living with HIV in sub-Saharan Africa and risk of preterm birth

EDCTP Project

TMA2020CDF-3192

EDCTP Program

EDCTP2

EDCTP Project Call

Career Development Fellowship (CDF)

Project Objectives

1. To compare vaginal virome diversity and composition of pregnant WLHIV versus pregnant WNLHIV. 2. Evaluate the relationship between vaginal virome and bacteriome. 3. To compare vaginal virome diversity and composition in WLHIV experiencing PTB versus WLHIV with healthy birth outcomes.

Study Design

Observational

Project Summary

Pregnant women living with HIV (WLHIV) are more likely to experience adverse birth outcomes, including preterm birth, than pregnant women not living with HIV (WNLHIV), thereby substantially contributing to maternal and infant morbidity in sub-Saharan Africa. Although alterations in vaginal bacteriome have been linked to preterm birth, they cannot fully explain the increased risk. Yet the role of vaginal pro-and eukaryotic viral communities, collectively referred to as “virome”, has not been rigorously evaluated. As the enteric virome is expanded in individuals living with HIV and modulates their gut bacteriome, we hypothesized that HIV infection in women of childbearing age would lead to an expanded vaginal virome, including the increased number and diversity of bacteriophages, which either directly or indirectly (through alteration of the bacterial microbiome) is associated with a higher risk of preterm birth in women with HIV. To test this hypothesis, we (1) compared the composition and diversity of the vaginal virome in pregnant women with HIV versus pregnant women without HIV, both with healthy birth outcomes, using shotgun metagenomic sequencing; (2) identified in vivo associations between vaginal viruses associated with HIV infection and bacteriome and validated key bacterial-viral interactions in vitro; and (3) compared vaginal virome diversity and composition of women with HIV experiencing preterm birth versus age-, parity- and antiretroviral regimen-matched women with HIV with healthy birth outcomes. This project leveraged the infrastructure and rigorous metadata of an ongoing pregnancy cohort study in Khayelitsha, Cape Town, South Africa. Pregnant women with and without HIV were enrolled during routine antenatal care visits and vaginal swabs, clinical and obstetric data are collected throughout pregnancy. At delivery, birth outcomes and other clinical data were collected. We found that vaginal DNA virome profiles were distinct between pregnant WLHIV and pregnant WNLHIV. The observed participant richness of viral operational taxonomic units (vOTUs) was lower in pregnant WLHIV compared to pregnant WNLHIV. Papillomavirus vOTUs were uniquely detected in pregnant WLHIV, while herpesvirus vOTUs were noted in pregnant WLHIV and pregnant WNLHIV to a similar extent. Strikingly, in both groups of women, the vaginal viral community was dominated by bacteriophages, making up almost 97% of the total vOTUs. Bacteriophage vOTUs with the predicted bacterial hosts Prevotella and Fannyhessea vaginae were more prevalent in pregnant WLHIV than pregnant WNLHIV, while those predicted to target Peptoniphilus were only present in pregnant WNLHIV. Bacteriophages with a predicted temperate lifestyle were more common than those predicted to be lytic in both groups of women. Predicted hosts of virulent phages in both groups included Lactobacillus mulieris, Prevotella bivia, Fannyhessea vaginae, Bifidobacterium swidsinskii, Dialister microaerophilus, and Sneathia vaginalis. Differences in vaginal viral diversity and composition suggest that, like the bacterial microbiome, the vaginal virome might also differ between pregnant WLHIV and pregnant WNLHIV. Future research is needed to understand its impact on reproductive health outcomes. Understanding the interplay between vaginal viruses, bacteria and preterm birth is relevant for developing novel diagnostics and interventions for improving birth outcomes among women with HIV, and to potentially decrease infant morbidity and mortality. Project website: https://idm.uct.ac.za/contacts/anna-ursula-happel-0/full?subsite=1506

Host Organisation

Department Institution Country
Pathology University of Cape Town ZA