Immune activation during pregnancy and contraception in HIV-infected Kenyan women

感染艾滋病毒的肯尼亚妇女怀孕期间的免疫激活和避孕

• 批准号: 8531309
• 负责人: Alison Christina Roxby
• 金额: $ 13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-20 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8531309
• 关键词: Affect; Africa; African; Age; Archives; Bacterial Vaginosis; Behavioral; Birth; CD4 Lymphocyte Count; CD8B1 gene; Candidiasis; Cells; Cervical; Clinical; Clinical Research; Collaborations; Communicable Diseases; Confounding Factors (Epidemiology); Contraceptive Agents; Contraceptive methods; Couples; Critical Pathways; Data; Development Plans; Diagnosis; Disease Progression; Enrollment; Environment; Epidemiology; Family Planning; Female; Genital system; Goals; HIV; HIV-1; HLA-DR Antigens; Heterosexuals; Human Herpesvirus 2; Human Milk; Hypersensitivity; Immune; Immune system; Immunologics; Immunology; Immunosuppression; Infection; Inflammatory; International; Kenya; Knowledge; Learning; Life; Link; Malaria; Measures; Medroxyprogesterone 17-Acetate; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Pathogenesis; Pathway interactions; Pattern; Peripheral; Postpartum Period; Postpartum Women; Pregnancy; Pregnant Women; Progesterone; Property; RNA; Recommendation; Recovery; Reproductive Health; Research; Research Design; Research Personnel; Research Training; Sampling; Seeds; Series; Sexually Transmitted Diseases; Swab; Syphilis; T-Cell Activation; T-Lymphocyte; T-Lymphocyte Subsets; Third Pregnancy Trimester; Training; Trichomonas Infections; Universities; Vagina; Washington; Woman; Women' s Group; antiretroviral therapy; base; career; career development; cohort; cytokine; experience; hormonal contraception; immune activation; improved; longitudinal analysis; male; patient oriented; patient oriented research; programs; reproductive; skills; transmission process

DESCRIPTION (provided by applicant): This proposal describes a 5-year training and research program that will allow the investigator to achieve her goal of becoming an independent patient-oriented researcher. She will use her expertise in international clinical research to improve reproductive health and survival of African women living with HIV-1. The proposed program will build on the candidate's extensive experience with international clinical research by improving her skills in study design and epidemiologic analysis of longitudinal data and improving her understanding of immunology and its application in patient-oriented research. The training plan incorporates an outstanding mentoring environment and involves collaboration between clinical researchers at the University of Washington and the University of Nairobi. Research Plan - HIV-1 infected pregnant women and contraception users have increased HIV-1 genital shedding and disease progression, but the mechanism behind these changes is poorly understood. Systemic T-cell immune activation has been linked to shedding and progression. We propose to measure systemic and local immune activation among these two groups of women. Aim 1) to determine whether postpartum hormonal contraception use affects systemic immune activation markers; Aim 2) to determine whether users of postpartum contraception have increased local immune activation, increased genital tract or breast milk HIV-1 shedding, and Aim 3) to describe differences in systemic immune activation in African HIV-1-seropositive and seronegative women throughout pregnancy and postpartum. The results of these analyses can be used to create a clearer picture of immunologic function in pregnancy and the postpartum period among HIV-1-infected women in Africa, to clarify mechanisms by which pregnancy and hormonal contraception may impact genital and breast milk HIV-1 shedding and disease progression, and ultimately to optimize recommendations for promoting appropriate family planning among these women. This opportunity will seed a larger research program to understand interactions of contraception, the immune system and HIV-1, and to use this knowledge to improve women's reproductive health.

描述（由申请人提供）：该提案描述了一项为期 5 年的培训和研究计划，该计划将使研究者能够实现成为一名独立的以患者为导向的研究人员的目标。她将利用自己在国际临床研究方面的专业知识来改善感染 HIV-1 的非洲妇女的生殖健康和生存。拟议的项目将建立在候选人在国际临床研究方面的丰富经验的基础上，通过提高她在研究设计和纵向数据流行病学分析方面的技能，并提高她对免疫学及其在以患者为导向的研究中的应用的理解。该培训计划包含了出色的指导环境，并涉及华盛顿大学和内罗毕大学的临床研究人员之间的合作。研究计划 - HIV-1 感染孕妇和避孕措施使用者增加了 HIV-1 生殖器脱落和疾病进展，但这些变化背后的机制尚不清楚。全身 T 细胞免疫激活与脱落和进展有关。我们建议测量这两组女性的全身和局部免疫激活。目标 1) 确定产后激素避孕的使用是否影响全身免疫激活标志物；目标 2) 确定产后避孕药使用者是否增加局部免疫激活、增加生殖道或母乳 HIV-1 脱落，目标 3) 描述非洲 HIV-1 血清阳性和血清阴性女性在整个怀孕和产后全身免疫激活的差异。这些分析的结果可用于更清晰地了解非洲 HIV-1 感染妇女怀孕和产后期的免疫功能，阐明怀孕和激素避孕可能影响生殖器和母乳 HIV-1 脱落和疾病进展的机制，并最终优化建议，以促进这些妇女采取适当的计划生育。这一机会将催生一个更大规模的研究计划，以了解避孕、免疫系统和 HIV-1 之间的相互作用，并利用这些知识来改善妇女的生殖健康。