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 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 are more likely to experience adverse birth outcomes, including preterm birth, than pregnant women without HIV, thereby substantially contributing to maternal and infant morbidity and mortality 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 hypothesise that HIV infection in women of childbearing age leads to an expanded vaginal virome, including increased number and diversity of bacteriophages, which either directly or indirectly (through alteration of the bacterial microbiota) is associated with a higher risk of preterm birth in women with HIV. To test this hypothesis, we will (1) compare 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) identify in vivo associations between vaginal viruses associated with HIV infection and bacteriome and validate key bacterial-viral interactions in vitro; and (3) compare 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 leverages the infrastructure and rigorous metadata of an ongoing pregnancy cohort study in Khayelitsha, Cape Town, South Africa. Pregnant women with and without HIV are 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 are collected. Year one of the project was focused on administrative tasks, including ethical approval, preparation of SOPs and other plans that ensure smooth running of the study, and recruitment and training of a PhD student. Sample collection is still ongoing as part of the parent study. We have optimised sequence independent single Primer Amplification to enable sequencing of the vaginal virome that may be quantitative and preserve the relative ratios of viral taxa, which does not occur with other commonly used methods such as Multiple Displacement Amplification and Rolling Circle Amplification. Up to year 2, administrative tasks and training of a PhD student have been completed. Sample collection for this project has also been completed. We optimized viral particle extraction from vaginal swabs. We then optimized a Sequence Independent Single Primer Amplification (SISPA) approach to enable deep sequencing of the viral metagenome that decreases the GC and genome size bias introduced by commonly used methods such as Multiple Displacement Amplification and Rolling Circle Amplification, while also yielding a greater diversity of near-complete metagenome-assembled genomes. This project is highly relevant to sub-Saharan Africa where HIV prevalence among pregnant women is substantial and pregnant women with HIV experience significantly higher risk of preterm birth than pregnant women without HIV. Infants born preterm experience poorer short and longer-term health outcomes, which are magnified in resource-limited settings such as sub-Saharan Africa. 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: http://www.idm.uct.ac.za/Anna-Ursula_Happel

Host Organisation

Current Organisation

University of Cape Town

Current Job Title

Junior Research Fellow

Biography

Publications