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

描述（由申请人提供）：本提案描述了一个为期5年的培训和研究计划，该计划将使研究者实现成为一名独立的以患者为导向的研究者的目标。她将利用她在国际临床研究方面的专业知识，改善非洲感染艾滋病毒1的妇女的生殖健康和生存。拟议的计划将建立在候选人的国际临床研究的丰富经验，通过提高她在研究设计和纵向数据的流行病学分析的技能，并提高她的免疫学及其在以患者为导向的研究中的应用的理解。培训计划包括一个出色的指导环境，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感染的孕妇和避孕药具使用者增加了HIV-1生殖器脱落和疾病进展，但对这些变化背后的机制知之甚少。全身性T细胞免疫激活与脱落和进展有关。我们建议测量这两组妇女的全身和局部免疫激活。目的1）确定产后使用激素避孕药是否影响全身免疫激活标志物;目的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，目的3）描述非洲HIV-1血清阳性和血清阴性妇女在整个妊娠期和产后全身免疫激活的差异。这些分析的结果可用于更清楚地了解非洲HIV-1感染妇女在怀孕和产后期间的免疫功能，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，并最终优化促进这些妇女适当计划生育的建议。这一机会将为一个更大的研究项目提供种子，以了解避孕、免疫系统和HIV-1的相互作用，并利用这些知识改善妇女的生殖健康。

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.