GH16-005, Zimbabwe, Implementing a sustainable adherence intervention, monitoring virologic suppression and drug resistance among HIV-infected adolescents receiving Antiretroviral treatment

GH16-005，津巴布韦，实施可持续的依从性干预，监测接受抗逆转录病毒治疗的艾滋病毒感染青少年的病毒学抑制和耐药性

• 批准号: 9505872
• 负责人: Chiratidzo Ellen Ndhlovu
• 金额: $ 50万
• 依托单位: COLLEGE OF HEALTH SCIS UNIV OF ZIMBABWE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-11-02 至 2021-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9505872
• 关键词: GH16; 005; Zimbabwe; Implementing; sustainable

Program Director/Principal Investigator (Last, First, Middle): Makadzange, Azure Tariro In 2014 UNAIDS set ambitious goals to achieve 90% virologic suppression rates among individuals on ART. In Zimbabwe this is an ambitious target particularly among adolescents; <5% of HIV infected individuals received HIV viral load (VL) testing in 2015 and treatment failure rates among adolescents range between 35-42%. Adolescents failing ART also have high rates of drug resistance. Scalable strategies to facilitate improved VL monitoring, adherence support and genotyping for those with persistent viremia are urgently needed. We have shown that dried blood spot (DBS) samples can be used for routine VL monitoring on existing technologies. We have also adapted an evidence based, widely used, cognitive behavioral therapy (CBT) adherence intervention (Life-Steps) for use in Zimbabwe and have identified a low-cost genotyping strategy that can facilitate detection of drug resistance mutations using already existing RT-PCR technology. We hypothesize that our proposed package of care will result in a decrease in virologic failure rates among adolescents. Our primary study objective is to determine if implementation of a package of care that includes DBS based viral load monitoring, coupled with an evidence-based intervention to improve ART adherence using cognitive- behavioral principles and genotyping for those with persistent viremia decreases 12-month virologic failure rates among HIV-infected adolescents compared with standard of care. We will also adapt and integrate Nzira Itsva for Adolescents (NI), a cultural adaptation of Life-Steps into routine care as an adherence support intervention for HIV infected adolescents, and implement a novel low-cost genotyping assay using Pan Degenerate Amplification and Adaptation (PANDAA) of viral RNA as a point mutation assay for the detection of drug resistance. Process and cost data will be collected for subsequent cost-analysis. The proposed intervention will be a two-arm cluster-randomized trial in Mashonaland West and Matabeleland North provinces of Zimbabwe. The units of randomization will be public and largely rural clinics within the provinces, with sites randomized to the intervention or to the standard of care. The study is anticipated to show that the use of DBS in routine monitoring of adolescents is feasible, to show that CBT if incorporated into routine counseling activities can complement viral load monitoring and genotyping to reduce treatment failure rates and preserve therapeutic options for infected adolescents. The results of this study will have important implications in Zimbabwe and other low-income countries in sub-Saharan Africa with a large proportion of HIV infected adolescents. The study will include young adolescents 10-14 years, as well as older adolescents 14-19 years and therefore provide data that will guide implementation of strategies for virologic success in the growing number of children who are surviving on ART into adolescents, as well as for behaviorally infected adolescents. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page

项目主任/主要研究者（最后，第一，中间）：Makadzange，Azure Tariro 2014年，联合国艾滋病规划署制定了雄心勃勃的目标，即在接受抗逆转录病毒治疗的人群中实现90%的病毒学抑制率。 津巴布韦这是一个雄心勃勃的目标，特别是在青少年中; <5%的艾滋病毒感染者接受 2015年艾滋病毒载量（VL）检测和青少年治疗失败率在35- 42%之间。 抗逆转录病毒疗法失败的青少年也有很高的耐药性。可扩展的战略，以促进改善VL 迫切需要对持续性病毒血症患者进行监测、依从性支持和基因分型。我们有 表明干血斑（DBS）样本可用于现有技术的常规VL监测。 我们还采用了基于证据的，广泛使用的，认知行为疗法（CBT）坚持 干预（生命步骤）在津巴布韦使用，并确定了一种低成本的基因分型策略， 使用现有的RT-PCR技术，有助于检测耐药突变。我们假设 我们提出的一揽子护理方案将导致青少年病毒学失败率的下降。我们 研究的主要目的是确定是否实施包括基于DBS的病毒治疗的一揽子治疗， 负荷监测，加上循证干预，以提高ART坚持使用认知- 持续性病毒血症患者的行为原则和基因分型减少了12个月的病毒学失败 与标准护理相比，艾滋病毒感染青少年的感染率。我们还将调整和整合Nemba Itsva for Adolescents（NI），一种将生活步骤融入日常护理的文化适应，作为坚持支持 艾滋病毒感染的青少年的干预，并实施一种新的低成本的基因分型检测使用泛 病毒RNA的简并扩增和适应（PANDAA）作为检测以下病毒的点突变试验： 耐药性将收集流程和成本数据，用于随后的成本分析。拟议 干预措施将是在西马绍纳兰省和北马塔贝莱兰省进行的一项双臂随机分组试验 津巴布韦。随机化单位将是各省内的公共诊所，主要是农村诊所，并有地点 随机分配到干预组或标准治疗组。这项研究预计将表明，使用DBS 在青少年的常规监测是可行的，以表明CBT如果纳入常规咨询 活动可以补充病毒载量监测和基因分型，以降低治疗失败率， 为受感染的青少年提供治疗选择。这项研究的结果将在以下方面产生重要影响： 津巴布韦等撒哈拉以南非洲低收入国家艾滋病毒感染者比例很大 青少年。这项研究将包括10-14岁的青少年，以及14-19岁的青少年。 因此，提供的数据将指导战略的实施，在不断增长的病毒学的成功。 接受抗逆转录病毒疗法存活至青少年的儿童人数，以及行为感染者人数 青少年。 OMB编号0925-0001/0002（2012年8月批准至2015年8月31日修订版）页码续页格式页码