The TENDAI study: Task shifting to treat depression and HIV medication nonadherence in low resource settings

背景艾滋病毒护理在津巴布韦等高流行率国家迅速分散， 努力扩大抗逆转录病毒疗法的获得，并在艾滋病毒感染者中实现病毒抑制 艾滋病毒/艾滋病（PLWH）。1，2在某些情况下，最大限度地坚持简单、负担得起的治疗方案尤为重要 三线抗逆转录病毒药物几乎不存在。与其他地方一样，津巴布韦的抑郁症在PLWH 3中很常见 也是抗逆转录病毒治疗依从性的一个关键障碍。4缺乏对抑郁症和抗逆转录病毒治疗效果差的干预措施 非专业人员可以提供的依从性。这些事实强调了公共卫生 重点关注那些患有抑郁症和接受ART治疗的可检测病毒载量的人的重要性。 前期工作我们进行了广泛的初步工作，以评估文化的适当性， 和可行性的阶梯式护理，任务转移干预治疗抑郁症和不遵守， 辛巴威.利用现有的非专业依从性顾问，这种干预与现有的津巴布韦 艾滋病护理路径。我们1）通过定性研究， 研究并在100名PLWH中进行了测试，5 2）开发了一种称为 TENDAI（在绍纳语中的意思是“感谢”）通过整合适应的坚持 用问题解决疗法干预抑郁症（一种简单的文化上可接受的治疗方法， 抑郁症在津巴布韦）6和3）成功地完成了一项开放试验，然后试点随机 TENDAI试验。7总之，这些研究表明， 抑郁症、依从性和HIV病毒抑制。我们的联合美国，英国和津巴布韦财团 汇集了艾滋病毒和抑郁症成功试验的历史。8 -10我们的建议得到了以下方面的强烈支持： 卫生部艾滋病和结核病股。设计：我们提出了TENDAI的双臂有效性RCT 在津巴布韦农村的艾滋病毒诊所对290名接受抗逆转录病毒疗法（一线、二线或三线治疗）的人进行干预， 可检测的病毒载量（=> 1000个病毒RNA拷贝）和临床显著的抑郁。关于TENDAI 将干预措施与增强的家庭护理（EUC）进行比较。12个月时的主要结局（目标1） 包括在每种情况下HIV病毒抑制比例、抗逆转录病毒疗法的依从性（电子评估 和通过干血斑中的ART检测）和抑郁症（通过当地有效的问卷进行评估 独立评估员）。我们还将测试（目标2）调节因子（性别，抑郁严重程度）， 治疗效果，并检查依从性和抑郁的变化作为对病毒影响的介导因素 镇压通过收集资源使用和成本数据，我们将研究 与EUC相比，我们的新疗法在减少抑郁症和潜在的更好的艾滋病毒结果方面 (Aim 3）。如果成功，随机对照试验的结果将使我们能够推荐一种坚持咨询的策略 和抑郁症护理在当地和东部和南部非洲地区。

Background. HIV care has been rapidly decentralized in high-prevalence countries like Zimbabwe, in the drive to expand access to antiretroviral therapy (ART) and to achieve viral suppression in people living with HIV/AIDS (PLWH).1,2 Optimising adherence to simple affordable regimens is especially critical in settings where third-line ART is barely available. Depression in Zimbabwe, like elsewhere, is common in PLWH3 and a key barrier to ART adherence.4 There is a dearth of interventions for depression and poor ART adherence which are feasible for non-specialists to deliver. These facts underscore the public health significance of focusing on those with depression and a detectable viral load receiving ART regimens. Preliminary work. We have conducted extensive preliminary work to evaluate the cultural appropriateness and feasibility of a stepped care, task-shifted intervention for treating depression and non-adherence in Zimbabwe. Using available lay adherence counselors, this intervention links with the existing Zimbabwean HIV care pathway. We 1) culturally adapted the Life-Steps adherence intervention through qualitative studies and tested it in 100 PLWH,5 2) developed a combined depression-adherence intervention called TENDAI (meaning ‘thankful’ in the Shona language) through integrating the adapted adherence intervention with Problem-Solving Therapy for depression (a simple culturally-acceptable treatment for depression used in Zimbabwe)6 and 3) successfully completed an open trial and then a pilot randomized trial of TENDAI.7 Together, these studies show feasibility, acceptability and potential beneficial effects on depression, adherence, and HIV viral suppression. Our combined US, UK and Zimbabwean consortium bring together a history of successful trials in HIV and depression.8-10 Our proposal is strongly endorsed by the Ministry of Health AIDS and TB Unit. Design: we propose a two-arm effectiveness RCT of the TENDAI intervention in HIV clinics in rural Zimbabwe in 290 people on ART (first, second or third line treatment) with a detectable viral load (=> 1000 viral RNA copies) and clinically significant depression. The TENDAI intervention will be compared to Enhanced Usual Care (EUC). Primary outcomes at 12 months (Aim 1) include proportion of HIV viral suppression in each condition, adherence to ART (assessed electronically and by ART detection in Dried Blood Spot), and depression (assessed via a locally validated questionnaire by an independent evaluator). We will also test (Aim 2) moderators (sex, depression severity) of the treatment effect, and examine changes in adherence and depression as mediators of the effect on viral suppression. Through collecting resource utilization and cost data we will examine the cost-effectiveness of our novel treatment compared to EUC on reduced depression and, potentially, on better HIV outcomes (Aim 3). If successful, the RCT results will enable us to recommend a strategy for adherence counseling and depression care locally and in the east and southern African region.