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

Pregnant women living with HIV (WLHIV) are more likely to experience adverse birth outcomes, including preterm birth (PTB), than pregnant women not living with HIV (WNLHIV), thereby substantially contributing to maternal and infant morbidity and mortality in sub-Saharan Africa (SSA). Alterations in vaginal bacteriome have been linked to PTB but 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. The enteric virome is expanded in individuals living with HIV and modulates their gut bacteriome.

Extrapolating from this, I 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 PTB risk in WLHIV.

To test this hypothesis, I will (1) compare the composition and diversity of the vaginal virome in pregnant WLHIV versus age- and parity-matched pregnant WNLHIV, both with healthy birth outcomes, using shotgun metagenomic sequencing to evaluate the effect of HIV infection on the vaginal virome; (2) identify in vivo associations between vaginal viruses associated with HIV infection (identified in Aim 1, quantified by qPCR) and bacteriome (leveraging available 16S rRNA gene sequencing and qPCR data) and validate key bacterial-viral interactions in vitro; and (3) compare vaginal virome diversity and composition of WLHIV experiencing PTB versus age-, parity- and antiretroviral regimen-matched WLHIV with normal birth outcomes to evaluate if changes in the vaginal virome are associated with PTB in WLHIV.

This project leverages the infrastructure and rigorous metadata of an ongoing pregnancy cohort study in Khayelitsha, Cape Town, South Africa.

Pregnant WLHIV and pregnant WNLHIV without any medical condition that would alter birth outcomes (besides HIV/use of antiretrovirals) are enrolled at 24-30 weeks gestational age (estimated by ultrasound) and vaginal swabs, clinical and obstetric data are collected. At delivery, gestational age, medical/obstetric conditions, infant sex, anthropometry, and abnormalities are collected.

This project is highly relevant in SSA where HIV prevalence among pregnant women is substantial and pregnant WLHIV experience significantly higher PTB risk than pregnant WNLHIV.

Infants born preterm experience poorer short and longer-term health outcomes, which are magnified in resource-limited settings such as SSA.

Understanding the interplay between vaginal viruses, bacteria and PTB is relevant for developing novel diagnostics and interventions for improving PTB among WLHIV, and to potentially decrease infant morbidity and mortality.