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.

患有艾滋病毒（PWLHIV）的孕妇更有可能经历不良的出生结果，包括早产（PTB），而不是孕妇不患HIV（PWNLHIV），从而实质上有助于撒哈拉以南非洲（SSA）的母亲和婴儿的发病率和死亡率。阴道细菌的改变阴道已与PTB有关，但这无法完全解释风险增加。我们发现虽然pwlhiv 阴道细菌的多样性增加和较高的细菌化患病率（BV）相关与PWNLHIV相比，细菌与PTB独立相关。因此，其他机制必须发挥作用。阴道病毒群落的作用，共同称为“病毒瘤”，尚未被评估。此外，需要研究HIV与ARV诱导的PTB的机制，以便可以确定干预措施以减轻这些风险。在HIV感染期间，肠道病毒素似乎正在改变。细菌的扩张，感染的病毒细菌与肠道和肠道细菌的免疫细胞扩张和感染增加有关多样性反映在病毒蛋白酶中。在非怀孕的WLHIV中，发现了四个主要病毒家族的病毒上部女性生殖道，但没有与Pwnlhiv进行比较，并且存在细菌。人类乳头瘤病毒（HPV）的较高患病率，尤其是高风险类型的患病率一直是与WNLHIV相比，在WLHIV中发现。但是，迄今为止，对艾滋病毒对集体的影响的数据有限阴道病毒群落，可能会改变。同样，很少有研究研究这种关系在阴道病毒蛋白和PTB之间。在这里，我们假设HIV感染导致阴道扩张病毒蛋白，包括直接或间接的细菌的数量和多样性（通过细菌微生物群的改变与PWLHIV中PTB风险较高有关。作为该提议的一部分项目，我们将利用基础架构和样本，以及两个正在进行的严格而广泛的数据南非开普敦的孕妇人群通过以下特定来解决这一假设目标：目的1：评估艾滋病毒，妊娠和抗逆转录病毒药物对阴道病毒蛋白多样性的影响作品。假设1：与Pwnlhiv相比，PWLHIV具有膨胀的阴道病毒蛋白目的2：评估PWLHIV中阴道噬菌体 - 宿主相互作用。假设2：病毒群落通过捕食者 - 纯化动力学改变阴道的细菌成分目标3：比较经历PTB与年龄的女性的阴道病毒蛋白多样性和组成和出生结果正常的奇偶校验妇女。假设3：阴道病毒蛋白的膨胀是负责提高PTB的比率。