Combination biomarkers for preventing HIV and adverse birth outcomes in a South African pregnancy cohort: implications for infant health
在南非妊娠队列中预防艾滋病毒和不良出生结局的组合生物标志物:对婴儿健康的影响
基本信息
- 批准号:9983241
- 负责人:
- 金额:$ 33.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-03 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAddressAfricanAge-MonthsAnaerobic BacteriaAnti-Retroviral AgentsBacteriaBacterial VaginosisBenefits and RisksBiologicalBiological AssayBiological MarkersBirthBreast FeedingChildChild HealthClinical InvestigatorClinical TrialsCollaborationsCommunicable DiseasesConsentDataDevelopmentDisadvantagedEnvironmentExposure toFemaleFetal DevelopmentGenital systemGrowthHIVHIV InfectionsHIV riskHigh Risk WomanHomeostasisImmunityImmunologicsImmunologyImpairmentIncidenceInfantInfant HealthInfectionInflammationInflammatoryInflammatory ResponseInstitutesInsulin ResistanceInterventionLactationLactobacillusLate pregnancyLeadLiquid substanceMeasuresMediator of activation proteinMetabolicMetabolic DiseasesMetabolismMetagenomicsMicrobeMitochondriaMucous MembraneNatural ImmunityNeurologicOutcomeParentsPharmaceutical PreparationsPlasmaPostpartum PeriodPredispositionPregnancyPregnancy OutcomePregnant WomenPremature BirthPremature InfantPremature LaborPreparationProvinceResearchResearch PersonnelRiskRisk FactorsSamplingScientistSecond Pregnancy TrimesterSouth AfricanSwabTechnologyTimeToxic effectUnderrepresented GroupsUniversitiesVaginaVisitWomanadipokinesadverse birth outcomesantenatalcervicovaginalchemokinecohortcytokineexperiencefetalglucose metabolismhigh riskinflammatory markerinflammatory milieuinnovationmicrobialmicrobial communitymicrobiomenatural Blastocyst Implantationneonatal morbidityneonatepre-exposure prophylaxispregnantpreventrecruitreproductive tractsafety and feasibilitytransmission processvaginal fluidvaginal microbiota
项目摘要
Abstract
Young pregnant women are at extremely high risk for acquiring HIV in late pregnancy and postpartum. Although
the precise mechanisms to explain the high risk of HIV during this time period is unknown, highly diverse vaginal
microbial communities and elevated genital inflammation have been associated with increased HIV susceptibility
among non-pregnant women. A balanced maternal inflammatory milieu and a Lactobacillus dominated vaginal
microbial communities have long been associated with optimal pregnancy outcomes. However, untimely or
excessive inflammatory response or diverse microbial communities in the vagina can lead to adverse birth
outcomes and/or HIV acquisition in at risk women. With heightened risk of HIV in pregnancy and postpartum,
pre-exposure prophylaxis (PrEP) is increasingly being used during these periods but the effects of maternal
PrEP use on child health outcomes remains underexplored. Here, we propose to use two unique cohorts of HIV-
uninfected pregnant women and their infants from Umlazi, KwaZulu-Natal, including those actively taking PrEP,
to better understand their risk factors for adverse birth outcomes and HIV acquisition as well as neonatal
morbidity. The specific aims are to: 1) assess whether vaginal microbial taxa or cytokines during gestation predict
risk of preterm labor and delivery in women at high risk for HIV. 16S rRNA gene sequencing and multiplex bead
arrays will be used to characterize the composition of vaginal microbial communities and soluble biomarkers of
genital inflammation in cervicovaginal swabs and SoftCup fluids collected from women at ~12.5-21.5 weeks’
gestation and relate these to incident preterm labor and delivery; 2) determine whether increased vaginal
microbial diversity and/or inflammation could explain the higher HIV risk during late pregnancy and early
postpartum. Microbial communities and cytokines from cervicovaginal swabs and SoftCup fluids collected at 14-
28 weeks’ gestation will be compared with those collected late pregnancy (38–40 weeks’ gestation) and 14 and
26 weeks postpartum to identify potential drivers of increased susceptibility HIV infection during these periods;
and 3) to determine the effects of antiretroviral exposure during gestation and breastfeeding on infant glucose
metabolism and innate immunity. Using samples collected from HIV-unexposed infants at 6 weeks and 12
months of age, plasma adipokine and cytokine levels and markers of insulin resistance will be compared in
antiretroviral (ARV)-exposed versus unexposed infants. The proposed research is innovative and will, for the
first time, determine whether specific vaginal anaerobic microbes and associated inflammation can predict which
women will deliver preterm or acquire HIV in our setting. Further, unique cohorts are available to examine the
immunological and metabolic effects of maternal ARV use during pregnancy on infant health without HIV
exposure, to inform risk-benefit analyses of maternal PrEP. This study has the potential to lead to more refined
interventions to mitigate risks of adverse birth outcomes, HIV acquisition and neonatal morbidity.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Heather Beryl Jaspan其他文献
Heather Beryl Jaspan的其他文献
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{{ truncateString('Heather Beryl Jaspan', 18)}}的其他基金
Penile viral and bacterial microbiome, inflammation and HIV susceptibility
阴茎病毒和细菌微生物组、炎症和艾滋病毒易感性
- 批准号:
10402631 - 财政年份:2022
- 资助金额:
$ 33.91万 - 项目类别:
Penile viral and bacterial microbiome, inflammation and HIV susceptibility
阴茎病毒和细菌微生物组、炎症和艾滋病毒易感性
- 批准号:
10646217 - 财政年份:2022
- 资助金额:
$ 33.91万 - 项目类别:
Bifidobacterium infantis supplementation in early life to improve immunity in infants exposed to HIV: a randomized, placebo-controlled, double-blind trial
生命早期补充婴儿双歧杆菌可提高感染 HIV 的婴儿的免疫力:一项随机、安慰剂对照、双盲试验
- 批准号:
10481469 - 财政年份:2022
- 资助金额:
$ 33.91万 - 项目类别:
Bifidobacterium infantis supplementation in early life to improve immunity in infants exposed to HIV: a randomized, placebo-controlled, double-blind trial
生命早期补充婴儿双歧杆菌可提高感染 HIV 的婴儿的免疫力:一项随机、安慰剂对照、双盲试验
- 批准号:
10632103 - 财政年份:2022
- 资助金额:
$ 33.91万 - 项目类别:
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:
10325550 - 财政年份:2021
- 资助金额:
$ 33.91万 - 项目类别:
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 - 财政年份:2021
- 资助金额:
$ 33.91万 - 项目类别:
Combination biomarkers for preventing HIV and adverse birth outcomes in a South African pregnancy cohort: implications for infant health
在南非妊娠队列中预防艾滋病毒和不良出生结局的组合生物标志物:对婴儿健康的影响
- 批准号:
10382303 - 财政年份:2020
- 资助金额:
$ 33.91万 - 项目类别:
Influence of maternal virome and HIV status on infant gut virome, growth and immunity
母体病毒组和 HIV 状态对婴儿肠道病毒组、生长和免疫的影响
- 批准号:
10267757 - 财政年份:2020
- 资助金额:
$ 33.91万 - 项目类别:
Influence of maternal virome and HIV status on infant gut virome, growth and immunity
母体病毒组和 HIV 状态对婴儿肠道病毒组、生长和免疫的影响
- 批准号:
10693179 - 财政年份:2020
- 资助金额:
$ 33.91万 - 项目类别:
Influence of maternal virome and HIV status on infant gut virome, growth and immunity
母体病毒组和 HIV 状态对婴儿肠道病毒组、生长和免疫的影响
- 批准号:
10161590 - 财政年份:2020
- 资助金额:
$ 33.91万 - 项目类别:
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