Use of Pharmacoepidemiology to Understand Predictors and Impact of Low-level Viremia in Persons with HIV in West Africa

利用药物流行病学了解西非艾滋病毒感染者低水平病毒血症的预测因子和影响

• 批准号: 10749658
• 负责人: Ebiere Clara HERBERTSON
• 金额: $ 6.54万
• 依托单位: NIGERIAN INSTITUTE OF MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749658
• 关键词: Acquired Immunodeficiency Syndrome; Adherence; Adult; Africa; Africa South of the Sahara; African; Anti-Retroviral Agents; Antiretroviral drug resistance; Appointment; Award; Blood; Caring; Cells; Cessation of life; Chronic; Clinical; Clinical Pharmacology; Collection; Communicable Diseases; Country; Data; Data Analyses; Databases; Development Plans; Diphosphates; Drug Exposure; Drug resistance; Dryness; Epidemic; Epidemiologist; Epidemiology; Event; Failure; Funding; Future; Goals; Guidelines; HIV; HIV-1; HIV-2; Hair; Individual; Intake; International; Intervention; K-Series Research Career Programs; Knowledge; Learning; Literature; Measurement; Measures; Mentors; Methods; Monitor; Names; Nigeria; Outcome; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacology; Pharmacy facility; Policies; Policy Maker; Predictive Value; Prevalence; Prospective cohort; Public Health; Records; Regimen; Reproductive Health; Research; Research Design; Research Personnel; Resistance; Resistance development; Resource-limited setting; Retrospective cohort; Scientist; Site; Source; Specialist; Spottings; Techniques; Tenofovir; Testing; Training; Treatment outcome; Urine; Viral; Viral Load result; Viral load measurement; Viral reservoir; Viremia; Virus Activation; Women' s Health; adolescent health; advanced analytics; antiretroviral therapy; biological sex; career; career development; clinical care; clinical prognosis; cohort; comorbidity; comparative; evidence base; experience; follow-up; improved; innovation; insight; longitudinal, prospective study; mathematical model; pharmacologic; pill; point of care; point of care testing; population health; prognostic value; scale up; skills; socioeconomics; statistics; study population; therapy outcome; translational physician; translational scientist; transmission process; treatment guidelines

PROJECT SUMMARY/ABSTRACT With this K43 Career Development Award, I will develop the skills necessary to reach my ultimate goal of becoming an independent investigator focused on the use of pharmacoepidemiology and experimental pharmacology to inform improved strategies for achieving sustained viral suppression in HIV treatment. Career Development Plan: My long-term career goal is to become an independently funded researcher with expertise in pharmacoepidemiology (epidemiology and clinical pharmacology) to inform improved strategies for achieving sustained viral suppression in HIV treatment. In the short-term during this K43 period, my goals are to Identify and characterize a retrospective cohort of PLWH in the IeDEA West Africa Database and determine the epidemiology and predictors of HIV-1, HIV-2 low-level viremia (LLV) in the cohort; and to determine the relationship between low-level viremia (LLV) and adherence to ART in a prospective cohort using 3 different adherence measures (pharmacy refill records (PRR), innovative urine-tenofovir POC test, and innovative TFV-DP in DBS). To attain these goals, I will be mentored during this K43 award period by a group of experienced career scientists: Dr. Cecile Lahiri, a clinician scientist whose focus is on HIV cure/eradication; Dr. Oliver Ezechi, a specialist in reproductive and population health whose focus is on the clinical impact of infectious diseases on women and adolescent health; Dr Antoine Jaquet, a clinician/epidemiologist with focus on the epidemiology of HIV and related chronic comorbidities; Dr. Igho Ofotokun an HIV translational clinician scientist with focus on women’s health and Dr. Castillo-Mancilla, a translational researcher focused on applied clinical pharmacology. For this K43 award, I will complete coursework and hands-on training in large data analysis and experimental pharmacology, I will also conduct research that exemplifies the undetectable = untransmissible (U=U) agenda with the goal of learning new ways of monitoring adherence to achieve effective HIV treatments that will stop transmission and eliminate HIV eventually. Merging my background in pharmacy practice in HIV care and infectious diseases, with advanced analytic skills, mathematical modelling, epidemiology, and experimental pharmacology from this K43, will give me the capacity for a career as an independent researcher. Research Plan: Emerging evidence suggests that persistent low-level viremia (LLV) in persons with HIV (PLWH) on antiretroviral therapy (ART) is a barrier to achieving the goal of zero transmission and eradication of HIV1-8, but not much is known about the impact of LLV on attaining the goal of viral suppression in West Africa; thus, this proposal aims to provide information vital to understand the impact of LLV in ART outcomes in West Africa. It will also be important to understand if differences exist between HIV-1 and HIV-2 treatment outcomes in the presence of LLV, since West Africa is one of the few regions in the world where HIV-2 is endemic. While literature is unanimous that sub-optimal adherence results in LLV, controversy surrounds the prognostic value of LLV for clinical outcomes. Some studies attribute the cause of LLV to drug resistance and reactivation of viral reservoirs, but other studies name these factors as consequences of LLV9-11. The ‘Undetectable=Untransmissible (U=U)’ concept is hinged on exploring pharmacologic, psycho- socio-economic, and other interventions to improve adherence and achieve undetectable viral load12,13. Individuals with LLV have been shown to be significantly less likely to subsequently achieve complete undetectable viral load. The upper limit of LLV (200-1000 copies/ml), has also been shown to be associated with virologic failure, development of resistance to ARVs, AIDS events and AIDS-related deaths1. Current WHO guidelines do not advise monitoring or treatment interventions even after repeated measurements of low-level viraemia. Consequently, patients are kept on failing ART regimens. Non-monitoring of LLV may result in an epidemic of resistance to currently used antiretrovirals and poor clinical prognosis in PLWH. Thus, it is vital to understand the predictors of LLV and its impact on PLWH, to inform improved clinical care of PLWH. Our proposed aims are: 1). To identify and characterize a cohort of from the IeDEA West Africa Database and determine the epidemiology and predictors of low-level viremia (LLV) in the cohort (for HIV-1 and HIV-2) and ii). Establish a prospective cohort of PLWH in Lagos, Nigeria, to estimate adherence to ART, using 3 different adherence measures (pharmacy refill records (PRR), innovative urine tenofovir POC test, and innovative TFV-DP in DBS). To accomplish this, We will assess the prevalence of LLV in a large West African database (IeDEA West Africa) and also determine the relationship between adherence with low-level viremia (LLV) in a cohort of 272 PLWH in Lagos, Nigeria and predict future LLV. This will be a 2-year follow-up prospective longitudinal study (3-monthly appointments for urine and DBS collection and 6- monthly viral load testing).

项目摘要/摘要 有了这个K43职业发展奖，我将发展达到实现最终目标所必需的技能 成为一名独立研究者，专注于使用药物电子学和实验 药理学以为改进的策略提供了在HIV治疗中持续抑制病毒的策略。 职业发展计划：我的长期职业目标是成为独立资助的研究人员 药物ePidemiology（流行病学和临床药理学）方面的专业知识，以告知改进的策略 用于在HIV治疗中实现持续的病毒抑制。在此K43时期的短期内，我的目标 是 在IEDEA西非数据库中识别和表征PLWH的回顾性队列 确定队列中HIV-1，HIV-2低级病毒血症（LLV）的流行病学和预测因子；然后 确定低级病毒血症（LLV）与前瞻性队列中艺术的遵守之间的关系 使用3种不同的依从性措施（药房补充记录（PRR），创新的尿液 - 荷诺堡POC测试， DBS中的创新TFV-DP）。为了实现这些目标，我将在此K43奖励期间被一个 经验丰富的职业科学家小组：塞西尔·拉希里（Cecile Lahiri）博士，临床科学家的重点是艾滋病毒 治愈/消除； Oliver Ezechi博士，生殖和人口健康专家，重点是 传染病对妇女和青少年健康的临床影响； Antoine Jaquet博士， 临床/流行病学家专注于艾滋病毒和相关慢性合并症的流行病学； Igho博士 Ofotokun A HIV翻译了临床科学家，专注于妇女健康和Castillo-Mancilla博士， 转化研究人员专注于应用临床药理学。对于这个K43奖，我将完成 大型数据分析和实验药理学的课程和动手培训，我还将进行 表明无法检测到的=不可及（U = U）议程的研究，目的是学习新 监测依从性以实现有效的艾滋病毒治疗方法，以停止传播和消除 艾滋病毒最终。合并我在艾滋病毒护理和传染病中的药房实践背景，与 高级分析技能，数学建模，流行病学和实验药理学 K43将使我成为独立研究人员职业的能力。 研究计划：新兴证据表明，患有患者 抗逆转录病毒疗法（ART）的HIV（PLWH）是实现零传播目标的障碍 以及消除HIV1-8，但对LLV对达到目标的影响不太了解 西非的病毒抑制；因此，该建议旨在提供至关重要的信息来了解 LLV对西非艺术成果的影响。了解是否是否 在LLV存在下，HIV-1和HIV-2治疗结果之间存在差异，因为 非洲是世界上少数几个HIV-2是地方性的地区之一。而文学是一致的 这种亚最佳依从性导致LLV，争议周围的LLV的预后价值 临床结果。一些研究将LLV原因归因于耐药性和重新激活 病毒储层，但其他研究将这些因素称为LLV9-11的后果。这 '不可检测的=不可转移（u = u）'概念在探索药物学，心理学方面取决于 社会经济和其他干预措施，以提高依从性并获得无法检测的病毒 负载12,13。 LLV的个体已被证明随后明显较小 达到完全无法检测到的病毒负荷。 LLV的上限（200-1000副本/毫升）也有 我们被证明与病毒学衰竭，对ARV的抵抗力的发展有关，艾滋病事件 和与艾滋病有关的死亡1。当前指南的当前指南不建议监视或治疗 即使在低级病毒血症的重复测量后进行干预。因此，患者是 继续失败的艺术方案。 LLV的非监控可能导致对 目前，PLWH中使用了抗逆转录病毒和临床预后不良。那是至关重要的 LLV的预测因素及其对PLWH的影响，以告知PLWH的临床护理。我们提出的 目的是：1）。 识别和表征来自IEDEA西非数据库的同类 确定队列中低级病毒血症（LLV）的流行病学和预测因子（对于HIV-1和 HIV-2）和II）。在尼日利亚拉各斯建立一个预期的PLWH队列，以估计遵守 艺术，使用3种不同的依从性措施（药房补充记录（PRR），创新的尿液Tenofovir DBS中的POC测试和创新的TFV-DP）。为此，我们将评估LLV的流行 大型西非数据库（IEDEA西非），也确定依从性之间的关系 在尼日利亚拉各斯的272 PLWH的队列中，有低水平的病毒血症（LLV），并预测未来的LLV。这将是一个 两年的随访前瞻性纵向研究（尿液和DBS收集3个月的任命和6-- 每月病毒负荷测试）。