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

HIV 感染对南非孕妇阴道病毒组和早产风险的影响

基本信息

批准号：
10325550
负责人：
Heather Beryl Jaspan
金额：
$ 67.71万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-09 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10325550
关键词：
Address Adenoviruses Adjuvant Adverse event Africa South of the Sahara Age American Anti-Retroviral Agents Antibiotics Antiviral Therapy Bacteria Bacterial Vaginosis Bacteriophages Base Sequence Birth CD4 Positive T Lymphocytes Cells Cervical Clustered Regularly Interspaced Short Palindromic Repeats Cohort Studies Communities Data Enteral Eukaryota Family Female genitalia Genome Genotype Gestational Age HIV HIV Infections HIV antiretroviral Herpesviridae High Prevalence High Risk Woman Human Papillomavirus Human papilloma virus infection Immune In Vitro Inflammation Infrastructure Intervention Link Maternal Age Measures MicroRNAs Modeling Morphology Nucleic acid sequencing Outcome Papillomavirus Peripheral Pharmaceutical Preparations Play Postpartum Period Pregnancy Pregnancy Outcome Pregnant Women Premature Birth Prokaryotic Cells Risk Risk Factors Role Sampling Shotguns South Africa South African Testing Therapeutic Vagina Viral Virus Woman adverse birth outcomes antiretroviral therapy bacterial community bacteriome cohort cytokine experience genetic signature high risk improved infant morbidity/mortality maternal morbidity metagenomic sequencing microbiota novel diagnostics parity particle point of care testing pre-exposure prophylaxis pregnant reproductive tract therapy development vaginal microbiota vector vaccine virome virus host interaction

项目摘要

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.

感染艾滋病毒的孕妇 (PWLHIV) 更有可能经历不良的分娩结局，包括早产 (PTB) 高于未感染艾滋病毒的孕妇 (PWNLHIV)，从而大大促进了撒哈拉以南非洲 (SSA) 的孕产妇和婴儿发病率和死亡率阴道细菌的变化。阴道感染与 PTB 有关，但这并不能完全解释 PWLHIV 风险增加的原因。阴道细菌多样性增加，细菌性阴道病（BV）相关的患病率更高与 PWNLHIV 细菌相比，HIV 感染与 PTB 独立相关。阴道病毒群落（统称为“病毒组”）的作用尚未发挥作用。此外，需要对 HIV 与 ARV 诱导的 PTB 的机制进行研究，以便可以确定干预措施来减轻这些风险。在 HIV 感染期间，肠道病毒组似乎发生了变化，噬菌体是感染病毒。细菌，与免疫细胞扩张以及肠道和肠道细菌炎症增加有关在非妊娠 WLHIV 中，发现了来自四个主要病毒家族的病毒。女性上生殖道，但没有与 PWNLHIV 进行比较，也没有噬菌体的存在尚未评估人乳头瘤病毒（HPV）的患病率较高，尤其是高危类型。然而，迄今为止，关于 HIV 对集体影响的数据有限。同样，很少有研究调查这种关系。在此我们假设 HIV 感染会导致阴道扩张。病毒组，包括噬菌体数量和多样性的增加，直接或间接（通过细菌微生物群的改变）与 PWLHIV 患者较高的 PTB 风险相关。项目中，我们将利用基础设施和样本，以及两个正在进行的严格和广泛的数据南非开普敦的孕妇队列通过以下具体方法来解决这一假设目标：目标 1：评估艾滋病毒、怀孕和抗逆转录病毒药物对阴道病毒组多样性的影响和假设 1：与 PWNLHIV 相比，PWLHIV 具有扩大的阴道病毒组。目标 2：评估 PWLHIV 中阴道噬菌体与宿主的相互作用。假设 2：病毒群落。通过捕食者-猎物动力学改变阴道的细菌成分目标 3：比较患有 PTB 的女性与年龄组的阴道病毒组多样性和组成。假设 3：阴道病毒组的扩张是正常的。 PTB 发病率增加的原因。