Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda.
Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda.
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DOI：
10.1371/journal.pmed.1002099
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发表时间：
2016-08
期刊：
影响因子：
15.8
通讯作者：
Partners Demonstration Project Team
中科院分区：
文献类型：
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作者：
Baeten JM;Heffron R;Kidoguchi L;Mugo NR;Katabira E;Bukusi EA;Asiimwe S;Haberer JE;Morton J;Ngure K;Bulya N;Odoyo J;Tindimwebwa E;Hendrix C;Marzinke MA;Ware NC;Wyatt MA;Morrison S;Haugen H;Mujugira A;Donnell D;Celum C;Partners Demonstration Project Team
基于抗逆转录病毒的HIV-1预防干预措施，包括降低HIV-1感染者传染性的抗逆转录病毒治疗（ART）和降低HIV-1未感染者易感性的暴露前预防（PrEP），在随机临床试验中显示出对HIV-1保护的高疗效。我们进行了一项前瞻性实施研究，以了解这些干预措施在分娩环境中的可行性和有效性。在2012年11月5日至2015年1月5日期间，我们在肯尼亚和乌干达的一项前瞻性实施研究中招募并跟踪了1，013对异性恋HIV-1血清不一致夫妇。ART和PrEP通过务实的策略提供，ART推广给所有夫妇，PrEP提供到HIV-1感染伴侣开始ART后6个月，允许时间达到病毒学抑制。在中位随访0.9年期间，有113对夫妇参加了研究，78%的伴侣开始了ART，97%的伴侣使用了PrEP。两种预防策略依从性的客观指标显示使用率较高（≥85%）。考虑到研究中观察到的HIV-1发病率较低，增加了一项额外分析，以比较观察到的发病率与根据模拟反事实模型估计的发病率，该模型使用既往HIV-1血清不一致夫妇前瞻性研究的数据构建。反事实模拟预测人群中预计有39.7例HIV-1感染，发病率为5.2/100人-年（95% CI 3.7-6.9）。然而，仅观察到2例HIV-1感染事件，发生率为0.2/100人-年（95% CI 0.0-0.9，p < 0.0001 vs预测值）。采用非同期比较HIV-1发病率是这一方法的一个潜在局限性;然而，招募未获得ART和PrEP的同期人群是不道德的。在非洲HIV-1血清不一致夫妇中持续使用ART之前，综合提供有时限的PrEP是可行的，表现出高吸收和依从性，并导致几乎消除HIV-1传播，每年的艾滋病感染率为<0.5% per year compared to an expected incidence of >5%。在一项前瞻性实施研究中，Jared Baeten及其同事调查了肯尼亚和乌干达的HIV-1血清不一致夫妇的抗逆转录病毒治疗和暴露前预防的综合提供。每年约有200万人感染艾滋病毒-1，大多数是通过性传播，大多数在非洲。抗逆转录病毒药物可有效治疗HIV-1感染，并且在过去5年中，关键临床试验表明，此类药物也可用于预防新感染，通过治疗HIV-1感染者以降低其传染性，并作为HIV-1未感染者的暴露前预防，以降低其易感性。尚未对非洲有效提供抗逆转录病毒药物预防艾滋病毒-1的模式进行评价。我们进行了一项前瞻性研究，在1,000多对HIV-1血清不一致的夫妇中使用抗逆转录病毒药物预防HIV-1（即，在肯尼亚和乌干达，夫妇中一人感染HIV-1，另一人未感染）;夫妇的行为和生物学特征使他们感染HIV-1的风险特别高，即使与HIV-1血清不一致的夫妇相比。所有夫妇的两名成员都提供抗逆转录病毒药物，并就其HIV-1预防益处进行咨询;该研究采取了务实和成本最小化的方法，在感染伴侣开始抗逆转录病毒治疗后6个月，停止对未感染伴侣使用暴露前预防。该项目的主要目标是评估交付模式的实施情况，包括吸收、依从性、持续性和安全性。在预期交付期的中途，很明显，这种方法非常成功，HIV-1的传播率大大低于预期（与模拟模型中的预期传播率相比降低了96%）。在临床研究中，抗逆转录病毒药物已被证明是预防HIV-1传播的有力工具;本研究的结果表明，在实施环境中采用实用的交付方法是可行的，具有高吸收率和坚持性，几乎可以消除HIV-1传播。大规模推广使用抗逆转录病毒药物预防艾滋病毒-1可能对减轻全球新的艾滋病毒-1感染负担产生重大影响。
Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings. Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7–6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0–0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP. Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year. In a prospective implementation study, Jared Baeten and colleagues investigate integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1–serodiscordant couples in Kenya and Uganda. Each year, approximately 2 million people become infected with HIV-1, most through sexual transmission and a majority in Africa. Antiretroviral medications effectively treat HIV-1 infection, and, in the last 5 y, pivotal clinical trials demonstrated that such medications can be used to prevent new infections as well, through treatment of HIV-1 infected persons to reduce their infectiousness and use as pre-exposure prophylaxis by HIV-1 uninfected persons to reduce their susceptibility. Models for effective delivery of antiretroviral medications for HIV-1 prevention in Africa have not been evaluated. We conducted a prospective study of a novel delivery model for use of antiretroviral medications for HIV-1 prevention among just over 1,000 HIV-1-serodiscordant couples (i.e., couples in which one member was HIV-1 infected and the other uninfected) in Kenya and Uganda; couples had behavioral and biologic characteristics that put them at particularly enhanced risk of HIV-1, even compared with HIV-1-serodiscordant couples in general. Both members of all couples were offered antiretroviral medications, and they were counseled on their HIV-1 prevention benefits; the study took a pragmatic and cost-minimizing approach, discontinuing the use of pre-exposure prophylaxis for the uninfected partner 6 mo after the infected partner initiated antiretroviral treatment. The primary goals of the project were to evaluate the implementation of the delivery model, including uptake, adherence, continuation, and safety. Part-way through the anticipated delivery period, it became clear that the approach was highly successful and that HIV-1 transmission rates were considerably lower than would have been anticipated (a 96% reduction compared to expected rates in a simulated model). Antiretroviral medications have proven to be a powerful tool for preventing HIV-1 spread in clinical research studies; the results of this study show that a practical delivery approach in an implementation setting is feasible with high uptake and adherence and can virtually eliminate HIV1- transmission. Wide-scale roll-out of use of antiretroviral medications for HIV-1 prevention could have substantial effects in reducing the global burden of new HIV-1 infections.