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.

项目总结/文摘

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.

激素避孕与抗逆转录病毒疗法之间的相互作用：更新的评论。

• 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