PrEP uptake/adherence to reduce periconception HIV risk for South African women

 描述（由申请人提供）：在艾滋病毒流行的环境中，许多未感染艾滋病毒的妇女选择与艾滋病毒感染者或血清状态未知的伴侣一起怀孕。对于不能依靠伴侣进行检测、启动和坚持抗逆转录病毒疗法的妇女来说，不使用避孕套的性行为使她面临感染艾滋病毒的高风险，并增加了围产期传染给孩子的风险。每日口服TDF/FTC PrEP可显著降低女性感染艾滋病毒的风险，是降低围产期感染艾滋病毒风险的唯一女性控制选择。了解每日口服PrEP对于寻求怀孕的未感染妇女是否可行，对于降低妇女及其子女的艾滋病毒发病率至关重要。我们建议进行一项单臂研究，为南非夸祖鲁-纳塔尔的350名未感染艾滋病毒的妇女提供每日口服PrEP，这些妇女报告了与感染或血清状态未知的伴侣一起怀孕的个人或伴侣计划。接受PrEP的妇女可以选择在怀孕期间继续PrEP。PrEP将作为更安全的概念包的一部分提供，包括基于夫妇的艾滋病毒咨询和检测。在目标1中，我们将评估启动PrEP的女性比例，并确定与吸收相关的因素。在目标2中，我们将评估围产期和妊娠随访期间客观测量的PrEP依从性。将使用血浆药物浓度和电子药丸帽评价依从性的水平、模式和相关性。我们的主要结果是保护性血浆替诺福韦浓度（> 40 ng/ml）的流行率。我们还将评估使用电子药丸帽分发药丸的平均依从性。从南非的形成性研究中，我们假设，在一个明确的终点（活产）的定义的风险期（围受孕，妊娠）内坚持一种经过验证的干预措施（TDF/FTC PrEP）将是高的（80%的访视时的保护性替诺福韦浓度，坚持>80%的处方药）。在目标3中，纵向定量数据和对最初高依从性和低依从性参与者的深入访谈将为我们的概念框架提供信息，以指导我们的概念框架。安慰剂对照试验将依从性确定为长期使用PrEP的主要挑战。然而，妇女渴望预防战略，使怀孕，我们假设，坚持一个行之有效的预防战略，在有限的时间内有一个健康的孩子的动机，将赋予药物水平所需的预防艾滋病毒传播。与PA 11 -275“发现、开发和测试新的干预措施以推进艾滋病毒预防和护理”相一致，该应用程序推进了艾滋病毒预防的组合方法，并针对受大流行影响严重的人群。该项目将确定每日口服PrEP是否是与风险伴侣一起怀孕的南非妇女的可行艾滋病毒预防策略。鉴于在受孕和怀孕期间感染艾滋病毒的影响，这是向妇女及其子女提供关键预防战略的重要一步。

 DESCRIPTION (provided by applicant): In HIV-endemic settings, many HIV-uninfected women choose to conceive with an HIV-infected or unknown- serostatus partner. For a woman who cannot depend on a partner to test, initiate and adhere to ART, sex without condoms puts her at high risk of acquiring HIV and increases the risk of perinatal transmission to her child. Daily, oral TDF/FTC PrEP dramatically reduces a woman's risk of HIV-acquisition and is the only female-controlled option for reducing her risk of periconception HIV-acquisition. Understanding whether daily, oral PrEP is feasible for uninfected women seeking pregnancy is critical to reducing HIV incidence among women and their children. We propose a single-arm study to offer daily, oral PrEP for periconception use to 350 HIV-uninfected women in KwaZulu-Natal, South Africa who report personal or partner plans for pregnancy with an infected or unknown serostatus partner. Women who become pregnant on PrEP will have the option to continue PrEP during pregnancy. PrEP will be offered as part of a safer conception package inclusive of couples-based HIV counseling and testing. In Aim 1, we will evaluate the proportion of women initiating PrEP and determine factors associated with uptake. In Aim 2, we will evaluate objectively-measured PrEP adherence during periconception and pregnancy follow-up. Level, patterns, and correlates of adherence will be evaluated using plasma drug concentrations and electronic pill caps. Our primary outcome is prevalence of protective plasma tenofovir concentrations (> 40 ng/ml). We will also evaluate median adherence to dispensed pills with electronic pill caps. From formative studies in South Africa, we hypothesize that adherence to a proven intervention (TDF/FTC PrEP) for a defined risk period (periconception, pregnancy) with a clear end point (live birth) will be high (protective tenofovir concentrations at 80% of visits, adherence to >80% of prescribed pills). In Aim 3, longitudinal quantitative data and in-depth interviews with initially high- and low-adhering participants will inform our conceptual framework for periconception PrEP uptake and adherence. Placebo-controlled trials identified adherence as a major challenge to long-term PrEP use. However, women are eager for prevention strategies that allow for conception, and we hypothesize that adherence to a proven prevention strategy, for a limited time with the motivation to have a healthy child, will confer drug levels required to prevent HIV transmission. Consistent with PA11-275 "Discovery, Development, & Testing of Novel Interventions to Advance HIV Prevention and Care", this application advances combination approaches to HIV- prevention and targets a population highly affected by the pandemic. This project will determine whether daily, oral PrEP is a feasible HIV-prevention strategy for South African women who conceive with risky partners. Given the repercussions of acquiring HIV during conception and pregnancy, this is an important step towards providing a key prevention strategy to women and their children.