Resistance testing versus adherence support for management of patients with virologic failure on first-line antiretroviral therapy in sub-Saharan Africa: An open-label randomized controlled trial

 描述(申请人提供)：在撒哈拉以南非洲，大约每3名接受抗逆转录病毒治疗(ART)的人中就有1人在抗逆转录病毒治疗开始两年内经历病毒学失败。2013年世界卫生组织(WHO)艾滋病毒治疗指南建议，在连续两次可检测到艾滋病毒RNA病毒载量(病毒载量)&1000拷贝/毫升后，将患者切换到二线治疗，以管理病毒学失败。随着病毒载量检测在撒哈拉以南非洲地区的扩大，这些建议可能会对治疗计划的可持续性产生重要影响。失败时缺乏伴随的耐药性测试有可能威胁艾滋病毒治疗计划的可持续性，因为1)促使携带野生型病毒的患者不必要地转向昂贵的二线治疗，以及2)尽管存在不明耐药性，但病毒载量低的患者仍继续接受一线治疗。迄今为止，撒哈拉以南非洲耐药性检测的成本效益研究产生了截然不同的结果，部分原因是缺乏有关耐药性检测有效性的原始数据。随着PEPFAR开始以可持续性为重点的第三阶段实施，至关重要的是制定一种以数据为导向的方法来管理撒哈拉以南非洲的病毒学失败，并最大限度地提高成功完成艾滋病毒连续护理的患者的比例。我们的首要目标是确定病毒学失败时的常规耐药性测试 在撒哈拉以南非洲提高了持续的病毒学抑制率，如果是这样的话，治疗方案的相对成本是多少。我们建议将撒哈拉以南非洲两个以PEPFAR为重点的国家的艾滋病毒诊所的患者纳入一项随机对照试验，以完成以下目标：目标1：评估基于耐药性测试的病毒学失败管理(耐药性测试ARM)与根据世卫组织指南基于病毒载量的管理(标准护理ARM)的有效性。我们假设，以耐药性检测为基础的治疗将优于以病毒检测失败9个月后病毒载量无法检测的患者的比例来衡量的护理管理标准。目的2：评估撒哈拉以南非洲病毒学失败的耐药性检测与基于病毒载量的管理的成本效益。我们假设耐药性测试将是具有成本效益的，因为通过减少二线治疗的使用，下游成本节省将抵消测试的成本。这项研究的结果将有助于为该地区的卫生部和多国艾滋病毒项目合作伙伴优化临床管理和资源分配。

 DESCRIPTION (provided by applicant): Approximately 1 in 3 people on antiretroviral therapy (ART) in sub-Saharan Africa experience virologic failure within two years of antiretroviral therapy treatment initiation. The 2013 World Health Organization (WHO) HIV treatment guidelines recommend management of virologic failure by switching patients to second line therapy after two consecutive detectable HIV RNA viral load (viral load) measurements >1,000 copies/mL. As viral load testing is scaled up in sub-Saharan Africa, these recommendations are likely to have important ramifications on the sustainability of treatment programs. The absence of concomitant resistance testing at the time of failure has the potential to threaten the sustainability of HIV treatment programs by 1) promoting unnecessary switching of patients with wild-type virus to costly second-line therapy and 2) continuing patients with low viral load on first-line therapy despite the presence of unidentified drug resistance. To date, cost-effectiveness studies of resistance testing in sub-Saharan Africa have generated contrasting results, partially due to lack of primary data on the efficacy of resistance testing. As PEPFAR embarks on its third phase of implementation with a focus on sustainability, it is critical to develop a data-driven approach to management of virologic failure in sub-Saharan Africa, and maximize the proportion of patients who sustain successful completion of the HIV continuum of care. Our over-arching goal is to determine whether routine resistance testing at virologic failure in sub-Saharan Africa improves rates of sustained virologic suppression, and if so, at what relative cost to treatment programs. We propose to enroll patients from HIV clinics in two PEPFAR-focus countries in sub-Saharan Africa into a randomized controlled trial to complete the following aims: Aim 1: Estimate the effectiveness of resistance testing-based management of virologic failure (resistance testing arm), versus viral-load based management per WHO guidelines (standard of care arm). We hypothesize that resistance testing-based management will be superior to standard of care management measured by the proportion of patients with undetectable viral load 9 months after detection of virologic failure. Aim 2: Evaluate the cost effectiveness of resistance-testing versus viral load-based management of virologic failure in sub-Saharan Africa. We hypothesize that resistance testing will be cost effective, because the cost of the assay will be offset by downstream cost savings through reduced use of second line therapy. Results of this study will help optimize clinical management and allocation of resources for ministries of health and multinational HIV program partners in the region.