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.

携带艾滋病毒(PWLHIV)的孕妇更有可能经历不利的分娩结局，包括 早产(PTB)，而不是携带艾滋病毒的孕妇(PWNLHIV)，从而大大有助于 撒哈拉以南非洲的母婴发病率和死亡率(SSA)。阴道细菌的变化 阴道与肺结核有关，但这不能完全解释风险增加的原因。我们发现，虽然PWLHIV 阴道细菌多样性增加，细菌性阴道病(BV)的患病率较高 与PWNLHIV相比，HIV感染与肺结核独立相关。因此，其他 机制必须发挥作用。阴道病毒群的作用，统称为“病毒体”，并没有 已经评估过了。此外，需要研究HIV与ARV诱导的肺结核的机制，以便 可以确定干预措施来缓解这些风险。 肠道病毒体似乎在感染艾滋病毒期间发生了变化。噬菌体的扩张，感染的病毒 细菌，已被认为与免疫细胞扩张和增加肠道和肠道细菌的炎症有关 多样性反映在病毒中。在未怀孕的WLHIV中，发现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，以及噬菌体的存在 没有进行评估。人类乳头瘤病毒(HPV)的高流行率，特别是高危类型的HPV 在WLHIV和WNLHIV中发现的比较。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，这很可能被改变。同样，很少有研究调查这种关系 阴道病毒症和肺结核之间的关系。这里我们假设HIV感染会导致阴道扩张 病毒体，包括增加噬菌体的数量和多样性，直接或间接(通过 细菌微生物群的改变)与PWLHIV中更高的肺结核风险相关。作为该提议的一部分 项目，我们将利用基础设施和样本，以及两个正在进行的数据的严谨和广泛 南非开普敦的一群孕妇用以下具体的方法来解决这一假设 目标： 目的1：评价HIV、妊娠和抗逆转录病毒药物对阴道病毒多样性和 组成。假设1：与PWNLHIV相比，PWLHIV有一个扩张的阴道病毒群 目的：探讨PWLHIV中阴道噬菌体与宿主的相互作用。假设2：病毒社区 通过捕食者-猎物动力学改变阴道的细菌成分 目的3：比较女性肺结核患者的阴道病毒多样性和组成与年龄的关系。 以及生育结果正常的胎次匹配的女性。假设3：阴道病毒体的扩张是 对肺结核发病率的增加负责。