Influence of HIV infection on vaginal virome and risk of preterm birth in pregnant South African women

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Pregnant women living with HIV (PWLHIV) are more likely to experience adverse birth outcomes, including preterm birth (PTB), than pregnant women not living with HIV (PWNLHIV), thereby substantially contributing to maternal and infant morbidity and mortality in sub-Saharan Africa (SSA). Alterations in bacteria of the vagina vaginal have been linked to PTB but this cannot fully explain the increased risk. We found that although PWLHIV had an increased vaginal bacterial diversity and higher prevalence of bacterial vaginosis (BV)-associated bacteria compared to PWNLHIV, HIV infection was independently associated with PTB. Therefore, other mechanisms must be in play. The role of vaginal viral communities, collectively referred to as “virome”, has not been evaluated. Additionally, the mechanisms of HIV- versus ARV-induced PTB needs to be investigated so that intervention measures can be identified to mitigate these risks. The enteric virome appears to be altered during HIV infection. Expansion of bacteriophages, viruses that infect bacteria, has been linked to immune cell expansion and increased inflammation in the gut and gut bacterial diversity is mirrored in the virome. In non-pregnant WLHIV, viruses from four major viral families were found in the upper female genital tract, but no comparison to PWNLHIV was made and the presence of bacteriophages was not evaluated. A higher prevalence of human papillomavirus (HPV), especially of high-risk types, has been found in WLHIV compared to WNLHIV. However, to date, limited data exist on the effect of HIV on the collective vaginal viral community, which is likely to be altered. Likewise, few studies have investigated the relationship between the vaginal virome and PTB. Here we hypothesise that HIV infection 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 PWLHIV. As part of this proposed project, we will leverage the infrastructure and samples, as well as rigorous and extensive data of two ongoing cohorts of pregnant women in Cape Town, South Africa to address this hypothesis with the following Specific Aims: Aim 1: To assess the effect of HIV, pregnancy and antiretroviral drugs on vaginal virome diversity and composition. Hypothesis 1: PWLHIV have an expanded vaginal virome compared to PWNLHIV Aim 2: To evaluate vaginal bacteriophage-host interactions in PWLHIV. Hypothesis 2: Viral communities alter the bacterial component of the vagina through predator-prey dynamics Aim 3: To compare vaginal virome diversity and composition in women experiencing PTB versus age- and parity-matched women with normal birth outcomes. Hypothesis 3: Expansion of the vaginal virome is responsible for increased rates of PTB.