Immunologic changes associated with three progestin-based contraceptives: characterizing immune profiles over one year and identifying factors that may alter HIV risk

与三种孕激素避孕药相关的免疫学变化：描述一年内的免疫特征并确定可能改变艾滋病毒风险的因素

• 批准号: 10440378
• 负责人: Lisa Blake Haddad
• 金额: $ 75.79万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10440378
• 关键词: 16S ribosomal RNA sequencing; AIDS/HIV problem; Adherence; Affect; African ancestry; Area; Bacterial Vaginosis; Biological Assay; Blood specimen; CCR5 gene; CD4 Positive T Lymphocytes; Cells; Chronic; Clinical; Contraceptive Agents; Contraceptive Usage; Contraceptive methods; Counseling; Cytometry; Data; Decision Making; Disease; Dose; Drug Kinetics; Epidemiology; Escherichia coli; Estrogen Antagonists; Estrogens; Etonogestrel; Exposure to; Female; Female genitalia; Flow Cytometry; Formulation; Genital; Genitalia; Gonadal Steroid Hormones; HIV; HIV Infections; HIV risk; Immune; Immune Targeting; Immune response; Immunologic Factors; Immunologic Markers; Immunologics; Implant; Incidence; Individual; Intrauterine Devices; Lead; Levonorgestrel; Link; Mediating; Medroxyprogesterone 17-Acetate; Menorrhagia; Methods; Mucous Membrane; Nature; Outcome; Outcome Study; Patients; Pharmacology; Polycystic Ovary Syndrome; Predisposition; Prevention; Progestins; Provider; Public Health; Publishing; Recommendation; Reporting; Reproductive Health; Research; Research Design; Research Project Grants; Risk; Risk Factors; Role; Sample Size; Sexually Transmitted Diseases; Testing; Time; Tissues; Translational Research; Vagina; Visit; Woman; aged; base; cohort; comparative; cytokine; endometriosis; epidemiology study; follow-up; global health; hormonal contraception; infection risk; modifiable risk; novel; personalized decision; prospective; recruit; reproductive; reproductive tract; response; translational potential; unintended pregnancy; vaginal microbiome; vaginal microbiota; volunteer

PROJECT SUMMARY/ABSTRACT This proposal outlines a 5-year translational research project to explore the mechanisms underlying the HIV risk associated with pharmacologic doses of exogenous sex hormones (via hormonal contraceptives). Emerging data suggests that certain hormonal contraceptives may induce mucosal and systemic immune changes that could increase the risk of infection with HIV. While several studies have aimed to characterize immunologic changes in women using hormonal contraceptives, the nature and the magnitude of these immune changes have not been adequately defined due to limitations in study design rigor, and small and statistically underpowered sample sizes. There is limited comprehensive data or comparative data on the effect of different types of contraceptives on innate and adaptive immunologic markers of HIV susceptibility. Without this research, we cannot effectively counsel our patients on contraceptive selection. Characterization of potential individual-level factors, such as the presence of bacterial vaginosis (BV), that may alter a woman's risk profile with contraceptive use, could lead to individualized decision-making about contraceptive choice and would have profound implications for global health especially in HIV-endemic areas. We propose to prospectively recruit cohorts of HIV-uninfected women initiating hormonal contraception to characterize systemic and lower genital track innate and adaptive immunologic changes that occur over the course of 1 year. This study will test the overarching hypothesis that hormonal contraceptives induce systemic and mucosal immune changes capable of altering susceptibilities and/or responses to diseases including HIV infection, and that these effects vary markedly in nature and magnitude by contraceptive type and will be modified by the vaginal microenvironment. The aims are: 1) To determine the immunologic alterations in female genital and systemic immune profile associated with depot medroxyprogesterone acetate (DMPA), Etonogestrel impant (Eng-Implant) and Levonorgestrel IUD (Lng-IUD). We hypothesize that HIV target immune cells within the female genital tract of HIV-uninfected at-risk women will increase following contraceptive initiation. Further, because the anticipated mucosal immune changes with progestin-only contraceptives are, to a large extent, mediated via estrogen suppression, we hypothesize the impact of the Lng-IUD (with minimal to no anti-estrogen effect) and Eng-Implant (with milder anti-estrogen effect) will be significantly less pronounced compared with that of DMPA. 2) To evaluate the vaginal microenvironment as a moderator of genital and systemic immune profile changes and changes in tissue infectivity following exposure to these three commonly used hormonal contraceptives. Based on our earlier findings, we hypothesize that immunologic changes induced with hormonal contraception will be more pronounced in the setting of BV. The outcomes of the proposed study could have significant global clinical implications for safe individualized contraceptive counseling and decision-making for women at risk for HIV/AIDS.

项目摘要/摘要 该提案概述了一个为期5年的翻译研究项目，旨在探索艾滋病毒的基础机制 与外源性激素的药理剂量相关的风险（通过激素避孕药）。 新兴数据表明，某些激素避孕药可能诱导粘膜和全身免疫 可能会增加艾滋病毒感染风险的变化。而几项研究的目的是表征 使用激素避孕药，这些性质和大小的女性免疫学变化 由于研究设计严格而小，并且 统计的样本量不足。有关效果的综合数据或比较数据有限 关于HIV易感性的先天和适应性免疫学标记的不同类型的避孕药。没有 这项研究，我们无法有效地为患者提供避孕药的选择。表征 潜在的个人水平因素，例如存在细菌性阴道病（BV），可能会改变女性的 使用避孕药的风险概况，可能导致有关避孕选择的个性化决策和 将对全球健康有深远的影响，尤其是在艾滋病毒流行地区。我们建议 前瞻性地招募艾滋病毒未感染的妇女发起荷尔蒙避孕的妇女以表征 在1个过程中发生的系统性和下生殖器轨道先天和适应性免疫学变化 年。这项研究将测试荷尔蒙避孕药诱导全身和 粘膜免疫变化能够改变易感性和/或对包括艾滋病毒在内的疾病的反应 感染，这些影响在性质和大小上因避孕类型而有明显变化，将是 通过阴道微环境修饰。目的是：1）确定 女性生殖器和全身免疫特征与乙酸盐菜酸盐（DMPA）相关， Etonogestel Invant（Eng-imptrant）和左旋省宫内节育器（LNG-IUD）。我们假设HIV靶标免疫 避孕药后，艾滋病毒未感染的艾滋病毒未感染的女性生殖道中的细胞将增加 引发。此外，由于预期的粘膜免疫因仅孕激素避孕药而变化是 在很大程度上，我们通过雌激素抑制介导，我们假设LNG-IUD的影响 没有抗雌激素效应）和工程植入术（具有温和的抗雌激素效应）将明显不那么明显 与DMPA相比。 2）评估阴道微环境作为生殖器和 暴露于这三种情况后，全身免疫轮廓变化和组织感染的变化 使用的激素避孕药。根据我们的早期发现，我们假设免疫学变化 在BV的情况下，用激素避孕诱导的诱导将更加明显。结果 拟议的研究可能对安全个性化避孕药具有重大的全球临床意义 为有艾滋病毒/艾滋病风险的妇女提供咨询和决策。

项目成果

Evaluating the impact of three progestin-based hormonal contraceptive methods on immunologic changes in the female genital tract and systemically (CHIME Study): a prospective cohort study protocol.

• DOI: 10.1186/s12905-022-02053-w
• 发表时间: 2022-11-18
• 期刊: BMC WOMENS HEALTH
• 影响因子: 2.5
• 作者: Haddad, Lisa B.;Herring, Gina Bailey;Mehta, C. Christina;Staple, Tyree;Young, Marisa R.;Govindaraj, Sakthivel;Velu, Vijayakumar;Smith, Alicia K.
• 通讯作者: Smith, Alicia K.

Interactions between Hormonal Contraception and Anti-Retroviral Therapy: An Updated Review.

• DOI: 10.1007/s13669-020-00289-7
• 发表时间: 2020-09
• 期刊: Current obstetrics and gynecology reports
• 影响因子: 0.5
• 作者: Krishna GR;Haddad LB
• 通讯作者: Haddad LB