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

• 批准号: 10667617
• 负责人: Heather Beryl Jaspan
• 金额: $ 85.07万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 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/10667617
• 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; Cell Count; Cells; Cervical; Clustered Regularly Interspaced Short Palindromic Repeats; Cohort Studies; Communities; Data; Development; Disease; Enteral; Eukaryota; Family; Female genitalia; Genome; Genotype; Gestational Age; HIV; HIV Infections; 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; Persons; 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; infant morbidity/mortality; maternal morbidity; metagenomic sequencing; microbiota; novel diagnostics; parity; particle; point of care testing; pre-exposure prophylaxis; pregnant; reproductive tract; risk mitigation; vaginal microbiota; vector vaccine; virome; virus host interaction; virus identification

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果，包括 早产（PTB）比未感染艾滋病毒的孕妇（PWNLHIV），从而大大有助于 撒哈拉以南非洲产妇和婴儿发病率和死亡率。阴道细菌的改变 阴道感染与PTB有关，但这不能完全解释风险增加。我们发现尽管PWLHIV 阴道细菌多样性增加，细菌性阴道病（BV）相关性 与PWNLHIV相比，HIV感染与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，统称为“病毒组”， 被评估。此外，还需要研究HIV与ARV诱导的PTB的机制， 可以确定干预措施来减轻这些风险。 肠道病毒组似乎在HIV感染过程中发生了改变。噬菌体和病毒的扩张 细菌，已被链接到免疫细胞扩张和增加炎症的肠道和肠道细菌 多样性反映在病毒组中。在非妊娠WLHIV中，发现了来自四个主要病毒家族的病毒， 上女性生殖道，但没有与PWNLHIV进行比较，噬菌体的存在 没有被评估。人乳头瘤病毒（HPV），特别是高危型的感染率较高， 与WNLHIV相比，然而，迄今为止，关于艾滋病毒对集体的影响的数据有限。 阴道病毒群落，这是可能被改变。同样，很少有研究调查这种关系， 阴道病毒组和肺结核之间的联系在这里，我们假设艾滋病毒感染导致阴道扩张 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中较高的PTB风险相关。作为建议的一部分， 项目，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，以解决这一假设与以下具体 目的： 目的1：评估HIV、妊娠和抗逆转录病毒药物对阴道病毒组多样性的影响， 混合物.假设1：与PWNLHIV相比，PWLHIV具有扩展的阴道病毒组 目的2：评价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-猎物动态改变阴道的细菌成分 目的3：比较经历PTB的女性与年龄的阴道病毒组多样性和组成。 和产次匹配的正常分娩结果的妇女。假设3：阴道病毒组的扩张是 导致肺结核发病率上升。