Impact of TB on Outcome of HIV in Pregnant Women

结核病对孕妇艾滋病毒感染结果的影响

• 批准号: 8526681
• 负责人: Richard E. Chaisson
• 金额: $ 15.64万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-28 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8526681
• 关键词: Adherence; Africa; African; Birth; Birth Weight; Blood; Blood specimen; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Caring; Cause of Death; Cell Count; Cessation of life; Child; Clinic; Clinical; Clinical Management; Cohort Studies; Comorbidity; Congenital Abnormality; Cytochrome P450; DNA Fingerprinting; Data; Diagnosis; Discipline of obstetrics; Disease; Disease Outcome; Drug Kinetics; Endometritis; Enrollment; Ensure; Enzymes; Evaluation; Generations; Gestational Age; Goals; HIV; HIV Infections; Health; Highly Active Antiretroviral Therapy; Hospitals; Hour; Incidence; Infant; Infant Mortality; Infection; Ingestion; Labor Onset; Laboratories; Length of Stay; Life; Low Birth Weight Infant; Measures; Morbidity - disease rate; Mothers; Mycobacterium tuberculosis; NNRTI-resistance; Neonatal; Nevirapine; Opportunistic Infections; Outcome; Participant; Patients; Perinatal; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Plasma; Pneumonia; Population; Populations at Risk; Postpartum Period; Pregnancy; Pregnancy Outcome; Pregnant Women; Prevalence; Prevention; Puerperal pyrexia; Recommendation; Recruitment Activity; Regimen; Research; Research Design; Research Priority; Restriction fragment length polymorphism; Rifampin; Risk; Sampling; Sepsis; Services; Severity of illness; Site; South Africa; Sputum; Symptoms; Techniques; Third Pregnancy Trimester; Time; Treatment Efficacy; Treatment Protocols; Tuberculosis; Umbilical Cord Blood; Up-Regulation; Urinary tract infection; Vertical Disease Transmission; Viral Load result; Vulnerable Populations; Woman; World Health Organization; Wound Infection; adverse outcome; base; case finding; cohort; efavirenz; infant death; infant outcome; mortality; neonate; non-nucleoside reverse transcriptase inhibitors; offspring; pharmacokinetic model; pregnant; premature; prenatal; prevent; prospective; public health relevance; resistance mutation; stillbirth; transmission process; tuberculosis drugs; tuberculosis treatment; ward

DESCRIPTION (provided by applicant): Tuberculosis (TB) is the leading cause of death in people with HIV infection and is prevalent in clinical settings where HIV care is provided. Among pregnant women with HIV infection, TB is an important cause of maternal morbidity and mortality, and may be associated with increased mother-to-child transmission (MTCT) of HIV and excess infant mortality. We have found that 2-3% of HIV-infected pregnant women in Soweto, South Africa, have previously undetected TB, increasing the risk of adverse outcomes for them and their offspring. Moreover, treatment of TB during pregnancy has the potential to interfere with the efficacy of treatment to prevent MTCT with the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine and efavirenz because of upregulation of P450 cytochromes by rifampin, the key drug in TB therapy. The goal of this proposal is to study the impact of TB/HIV co-infection in pregnancy on maternal and infant outcomes, and to characterize the impact of TB treatment using rifampin on the pharmacokinetics and pharmacodynamics of NNRTIs used for prevention of MTCT. We will assemble a prospective cohort of 250 HIV- and TB-infected pregnant women recruited from antenatal clinics in Soweto and the obstetrics ward at the Chris Hani Baragwanath Hospital and 500 HIV-infected pregnant women without TB matched based on gestational age and site of enrollment. Participants will undergo baseline clinical and laboratory evaluations and will be followed through pregnancy, labor and delivery and 6 months post-partum to record maternal and infant HIV, TB and overall outcomes. We will determine the association of TB and maternal CD4 counts and HIV viral loads, HIV-related complications and deaths, and transmission of HIV to infants. We will also assess the impact of TB on obstetric and infant outcomes, including prematurity, low birth weight, post-partum infections and survival. Additionally, we will conduct pharmacokinetic sampling over 48 hours after the onset of labor and use pharmacokinetic modeling to determine the impact of concomitant rifampin use on NNRTI exposure and efficacy during pregnancy and the peripartum period. This study will yield extremely important data on the outcomes of TB and its treatment in HIV- infected, pregnant women that will be widely applicable in Africa and other regions where women and infants are threatened by this deadly co-infection. PUBLIC HEALTH RELEVANCE: This project will guide strategies for managing HIV and TB in a highly vulnerable population, pregnant women and their offspring. The project is directly responsive to research priorities identified by the World Health Organization regarding HIV pharmacovigilance, including evaluation of co-morbidities such as TB in pregnant women living with HIV and generation of pharmacology profiles in this at-risk population to ensure that WHO HIV treatment recommendations are appropriate. Determining the impact of maternal TB disease and treatment on maternal and infant HIV outcomes will guide clinical management of HIV/TB co-infected pregnant women and their infants; evaluating the impact of maternal TB disease and treatment on pregnancy and perinatal outcomes will help identify obstetric and neonatal complications of maternal TB that will help practitioners optimize prenatal and neonatal care; and determination of the impact of TB treatment on HIV drugs will inform decisions on treatment to prevent mother-to- child HIV transmission.

描述（由申请人提供）：结核病（TB）是艾滋病毒感染患者死亡的主要原因，在提供艾滋病毒护理的临床环境中很普遍。在患有艾滋病毒感染的孕妇中，结核病是孕产妇发病率和死亡率的重要原因，可能与艾滋病毒和婴儿死亡率过多的母亲到孩子传播（MTCT）增加有关。我们发现，南非索韦托的艾滋病毒感染的孕妇中有2-3％以前未被发现结核病，增加了她们及其后代不良后果的风险。此外，怀孕期间的结核病治疗可能会干扰治疗的功效，以防止MTCT与非核苷逆转录酶抑制剂（NNRTIS）Nevirapine和efavirenz，并且由于Rifampin（由Rifampin）在TB治疗中键入P450细胞色素，因为P450细胞联合药物的上调。该提案的目的是研究妊娠中结核病/HIV共同感染对孕产妇和婴儿结局的影响，并使用利福平对TB治疗的影响，对RIFAMPIN对用于预防MTCT的NNRTIS的药代动力学和药效学。我们将组建一个前瞻性队列，由索韦托的产前诊所和Chris Hani Baragwanath医院的妇女和TB感染的孕妇组成，由Chris Hani Baragwanath医院和500名未经TB的HIV感染孕妇招募，该孕妇基于性业年龄和注册者。参与者将接受基线临床和实验室评估，并将在怀孕，劳动和分娩后进行遵循，并在产后6个月以记录孕产妇和婴儿艾滋病毒，结核病和整体结果。我们将确定结核病和母体CD4计数以及HIV病毒载荷，与HIV相关的并发症和死亡以及HIV向婴儿传播的关联。我们还将评估结核病对产科和婴儿结果的影响，包括早产，低出生体重，产后感染和生存。此外，我们将在劳动发作后48小时内进行药代动力学采样，并使用药代动力学建模来确定利福平伴随利福丁对妊娠期间和peripartum期间NNRTI暴露和疗效的影响。这项研究将产生有关结核病结果及其在艾滋病毒感染的孕妇中的治疗的极为重要数据，这些数据将广泛适用于非洲和其他受到这种致命共同感染威胁的妇女和婴儿的地区。 公共卫生相关性：该项目将指导在高度脆弱的人口，孕妇及其后代管理艾滋病毒和结核病的策略。该项目直接响应世界卫生组织确定的有关HIV药物警戒的研究优先级，包括评估HIV孕妇中的结核病和TB等合并症，以及该高危人群中的药理学概况，以确保艾滋病毒治疗建议适合谁。确定母体结核病和治疗对母亲和婴儿HIV结果的影响将指导HIV/TB共感染的孕妇及其婴儿的临床管理；评估母体结核病和治疗对妊娠和围产期结局的影响将有助于确定母体结核病的产科和新生儿并发症，这将有助于从业者优化产前和新生儿护理；并确定结核病治疗对艾滋病毒药物的影响将为治疗的决定提供依据，以防止母亲艾滋病毒传播。