Hormonal contraception, pre-exposure prophylaxis, and HIV-1 protection

激素避孕、暴露前预防和 HIV-1 防护

• 批准号: 8537737
• 负责人: Jared Baeten
• 金额: $ 24.03万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8537737
• 关键词: Accounting; Address; Adherence; Advocate; Africa; African; Age; Archives; Behavioral; Child; Contraceptive Agents; Contraceptive Usage; Contraceptive methods; Couples; Critiques; DNA; Data; Data Analyses; Data Set; Development; Effectiveness; Ensure; Epidemiologic Studies; Exposure to; Family Planning; Female; HIV; HIV-1; Heterosexuals; Hormonal; Incidence; Infection; Injectable; Knowledge; Measures; Methods; Modification; Multivariate Analysis; Oral; Persons; Plasma; Policy Research; Positioning Attribute; Predisposition; Pregnancy; Pregnancy Outcome; Prevention; Prevention strategy; Prophylactic treatment; Public Health; Reporting; Research; Research Design; Risk; Safety; Sampling; Scientist; Seminal fluid; Sex Behavior; Simplexvirus; Subgroup; Swab; Tenofovir; Testing; Unsafe Sex; Vagina; Woman; Women' s Health; Y Chromosome; antiretroviral therapy; base; condoms; contraceptive effectiveness; emtricitabine; hormonal contraception; improved; male; men; pregnancy prevention; prevent; protective effect; public health relevance; randomized placebo controlled trial; randomized trial; reproductive; response; transmission process

DESCRIPTION (provided by applicant): Women account for nearly one-half of new HIV-1 infections worldwide, including the majority of infections in Africa. Heterosexual intercourse is responsible for most HIV-1 transmissions to women, and the majority of HIV-1 infected women are of reproductive age. Biologic and epidemiological studies have suggested that the use of hormonal contraception may influence HIV-1 susceptibility and infectiousness, but the relationship has not been consistent across all studies. Understanding the relationship between hormonal contraceptive use and HIV-1 risk is a topic of public health importance, because effective family planning is central to initiatives to improve the health of women and children worldwide. A central critique of studies of the hormonal contraception-HIV-1 relationship has been that condom use, particularly accurate reporting of use, could differ for contraceptive users versus non-users, a bias that could result in increased HIV-1 risk. Pre-exposure prophylaxis (PrEP), in which HIV-1 uninfected persons use antiretrovirals to protect against sexual HIV-1 acquisition, is a promising new HIV-1 prevention strategy. We recently demonstrated in the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP among HIV-1 uninfected partners in 4758 African heterosexual HIV-1 serodiscordant couples, that oral emtricitabine/tenofovir (FTC/TDF) PrEP reduced HIV-1 acquisition risk by 75% (p<0.001). However, not all PrEP trials have shown HIV-1 protection; a number of hypotheses have been proposed to explain divergent PrEP trial results in women, primarily adherence to PrEP but also evidence to suggest possible biologic or behavioral interactions between PrEP and hormonal contraception. Whether any potential increase in HIV-1 risk due to contraceptive method could be offset by PrEP use is a critical question for the development of "dual protection" strategies (i.e., providing protection against HIV-1 and pregnancy), as is whether PrEP and hormonal contraceptives interact in a way that might undermine their HIV- 1 or pregnancy prevention effects. We are uniquely positioned to analyze data and samples from the Partners PrEP Study to inform key questions exploring the interactions of hormonal contraceptive use, PrEP use, and HIV-1 and pregnancy outcomes. Specifically, we will: 1) assess the effect of hormonal contraception on risk of HIV-1 acquisition in women and transmission from women to their male partners, 2) determine whether a) HIV-1 protection by PrEP is diminished in contraceptive users and b) PrEP reduces the pregnancy- prevention effects of contraception, and 3) among HIV-1 uninfected women, measure bias in sexual behavioral reporting for hormonal contraceptive users vs. non-users, which could explain whether increased HIV-1 risk for hormonal users is primarily a biologic or behavioral effect - an important step for prioritizing research and policy responses. The proposed analyses offer an unprecedented opportunity to examine important global public health questions: what is the spectrum of risk associated with use of different contraceptives, can antiretrovirals be used safety for prevention in conjunction with common hormonal contraceptive methods, and can PrEP offset potential increased HIV-1 risk associated with hormonal contraceptive use? The project team has the expertise to address these timely questions with this dataset. The results of the proposed projects will fill critical knowledge gaps that are key to the health of women worldwide and are urgently needed by family planning advocates, HIV-1 prevention scientists, clinicians, and policymakers in order to develop clear messages for women using hormonal contraception and to provide the safest contraceptive options to women with and at-risk for HIV-1.

描述（由申请人提供）：全球新发 HIV-1 感染者中，女性占近一半，其中包括非洲的大部分感染者。异性性交是大多数 HIV-1 传播给女性的原因，大多数 HIV-1 感染女性处于育龄期。生物学和流行病学研究表明，使用激素避孕可能会影响 HIV-1 的易感性和传染性，但所有研究中的这种关系并不一致。了解激素避孕药的使用与 HIV-1 风险之间的关系是一个具有公共卫生重要性的话题，因为有效的计划生育对于改善全世界妇女和儿童健康的举措至关重要。对激素避孕药与 HIV-1 关系的研究的一个主要批评是，避孕套的使用，特别是准确的使用报告，对于避孕药使用者和非使用者来说可能有所不同，这种偏见可能导致 HIV-1 风险增加。 暴露前预防 (PrEP) 是一种很有前景的新型 HIV-1 预防策略，其中未感染 HIV-1 的人使用抗逆转录病毒药物来防止性传播 HIV-1。我们最近在合作伙伴 PrEP 研究中证明，口服恩曲他滨/替诺福韦 (FTC/TDF) PrEP 减少了 HIV-1 感染，该研究是一项在 4758 名非洲异性 HIV-1 血清不一致夫妇中未感染 HIV-1 的伴侣中进行的随机、安慰剂对照 PrEP 试验。风险降低 75% (p<0.001)。然而，并非所有 PrEP 试验都显示出 HIV-1 保护作用；人们提出了许多假设来解释女性中不同的 PrEP 试验结果，主要是 PrEP 的依从性，但也有证据表明 PrEP 和激素避孕之间可能存在生物或行为相互作用。 对于制定“双重保护”策略（即提供针对 HIV-1 和怀孕的保护）的一个关键问题是，由于避孕方法而导致的 HIV-1 风险的任何潜在增加是否可以通过 PrEP 的使用来抵消，这是制定“双重保护”策略（即提供针对 HIV-1 和怀孕的保护）的一个关键问题，同样重要的是 PrEP 和 PrEP 是否可以预防 HIV-1 风险。激素避孕药的相互作用可能会削弱其 HIV-1 或妊娠预防作用。 我们具有独特的优势，可以分析合作伙伴 PrEP 研究的数据和样本，为探索激素避孕药使用、PrEP 使用以及 HIV-1 和妊娠结局之间相互作用的关键问题提供信息。具体来说，我们将：1) 评估激素避孕对女性感染 HIV-1 以及从女性传播给男性伴侣的风险的影响，2) 确定 a) PrEP 对 HIV-1 的保护是否在避孕药具使用者中减弱，b) ) PrEP 降低了避孕的妊娠预防效果，并且 3) 在未感染 HIV-1 的女性中，测量激素避孕药使用者与非使用者的性行为报告偏差，这可以解释是否激素使用者的 HIV-1 风险增加主要是生物或行为效应——这是确定研究和政策反应优先顺序的重要一步。拟议的分析为研究重要的全球公共卫生问题提供了前所未有的机会：与使用不同避孕药具相关的风险范围是什么，抗逆转录病毒药物是否可以与常见的激素避孕方法一起安全地用于预防，以及 PrEP 是否可以抵消潜在的艾滋病毒增加-1 与使用激素避孕药相关的风险？项目团队拥有利用该数据集解决这些及时问题的专业知识。拟议项目的结果将填补关键的知识空白 这些对于全世界妇女的健康至关重要，并且是计划生育倡导者、HIV-1 预防科学家、临床医生和政策制定者迫切需要的，以便向使用激素避孕的妇女传达明确的信息，并为患有以下疾病的妇女提供最安全的避孕选择：有感染 HIV-1 的风险。