Addressing Major HIV Prevention and Health Outcomes Questions in an Era of Universal ART: Mentoring in a Community-Randomized Trial

解决普遍抗逆转录病毒治疗时代的主要艾滋病毒预防和健康结果问题：社区随机试验中的指导

• 批准号: 10112810
• 负责人: SHAHIN LOCKMAN
• 金额: $ 18.89万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2022-07-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10112810
• 关键词: AIDS prevention; Address; Adopted; Adult; Affect; Africa; Africa South of the Sahara; Anti-Retroviral Agents; Antibiotics; Botswana; CD4 Lymphocyte Count; Caring; Child; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Communities; Country; Data; Disease; Enrollment; Epidemic; Faculty; Feasibility Studies; Funding; Grant; HIV; HIV Infections; HIV Seronegativity; HIV diagnosis; HIV prevention trial; HIV-1; Health; High Prevalence; Household; Human immunodeficiency virus test; Hypertension; Incidence; Individual; Infant; Infrastructure; International Maternal Pediatric Adolescent AIDS Clinical Trials; Intervention; Interview; Lead; Longitudinal cohort; Machine Learning; Male Circumcision; Malignant Neoplasms; Measures; Mentors; Mothers; Observational Study; Outcome; Persons; Population; Pregnancy; Pregnant Women; Prevalence; Prevention; Prevention approach; Prevention trial; Protocols documentation; Public Health; Qualitative Methods; Randomized; Regimen; Research; Research Personnel; Resources; Risk; Sampling; Secure; Services; Students; Tenofovir; Time; Treatment Protocols; antiretroviral therapy; base; cancer risk; clinically relevant; cohort; community intervention; efavirenz; emtricitabine; epidemiology study; follow-up; high risk; meetings; patient oriented; patient oriented research; perinatal HIV; point of care; population based; pre-exposure prophylaxis; preventive intervention; randomized trial; treatment program; trial design; uptake; virology

SUMMARY / ABSTRACT Dr. Lockman has a long and successful track record mentoring more than 20 fellows, junior faculty, and students from the US and Africa in patient-oriented HIV research, seven of whom have secured K funding and four of whom are now R-funded . She is deeply committed to continuing and expanding this mentoring, which serves as the primary impetus for this K24 grant. Her mentees will have access to a wealth of research opportunities in the context of the many large HIV-focused clinical trials and studies that Dr. Lockman leads (and led over the past 18 years) in Botswana and elsewhere, ranging from randomized trials of antiretroviral or antibiotic regimens (many in pregnant women and their infants) to observational and epidemiologic studies of clinical outcomes among HIV-infected adults and HIV-exposed children. In the proposed K24, she will leverage the unique and extensive infrastructure, data and samples from a large ongoing randomized HIV combination prevention trial that she and others are conducting in 30 communities in Botswana (total population 180,000 with longitudinal cohort of 12,000 adults), in order to mentor investigators from Botswana and the US on pressing questions of substantial public health and clinical relevance to the severe epidemic still affecting sub-Saharan Africa. For context, UNAIDS is promoting high levels (90% or greater) of HIV diagnosis, antiretroviral treatment (ART) coverage, and virologic suppression (“90-90-90” targets) to end the HIV epidemic. However, despite nearly meeting these targets in Botswana, we observe annual HIV incidence >1%. Furthermore, with more than 15% of the adult population of Botswana on ART (and recent implementation of universal ART), it is essential that we understand the implications of widespread treatment for clinical outcomes and non-communicable disease incidence in persons living with HIV at the population level. We will therefore: a) Characterize adults with recent HIV infection using predictive analysis, in order to identify groups at highest risk for HIV acquisition in the current epidemic, and augment our understanding with individual in-depth interviews with recently- infected adults; b) Study the feasibility, acceptability, and uptake of a targeted approach to TDF/FTC pre- exposure prophylaxis, offered to HIV-negative persons meeting this high-risk profile; c) Evaluate the impact of HIV (and of early ART) on clinical outcomes, including c ancer incidence and hypertension prevalence in HIV-infected vs. HIV-uninfected adults, and HIV-related outcomes among persons starting dolutegravir- vs. efavirenz-based ART. In addition, Dr. Lockman will also mentor junior investigators on projects nested within a new large randomized IMPAACT trial of 3 antiretroviral regimens in pregnancy that that she leads, and in prior large perinatal HIV studies in Botswana that enrolled more than 9,000 mother-infant pairs. This K24 is critical, to support the protected time and resources that are required for Dr. Lockman to mentor junior investigators from both the US and Botswana in patient-oriented research.

总结/摘要 洛克曼博士有一个长期和成功的跟踪记录指导超过20名研究员，初级教师， 来自美国和非洲的学生在以病人为导向的艾滋病研究， 其中7人获得了K基金 其中四个现在是R基金资助的 .她坚定地致力于继续和扩大这种指导， 这是K24资助的主要推动力。她的学员将有机会获得丰富的 研究机会的背景下，许多大型艾滋病毒为重点的临床试验和研究，博士 洛克曼在博茨瓦纳和其他地方领导（并在过去18年中领导），从随机 抗逆转录病毒或抗生素治疗方案的试验（许多在孕妇及其婴儿中进行）， 以及艾滋病毒感染成人和艾滋病毒暴露儿童临床结局的流行病学研究。在 在拟议的K24中，她将利用来自 她和其他人正在30个国家进行的一项大型随机艾滋病毒联合预防试验， 博茨瓦纳的社区（总人口180 000人，纵向队列12 000名成年人），以便 指导来自博茨瓦纳和美国的调查人员处理重大公共卫生问题， 与仍在影响撒哈拉以南非洲的严重流行病的临床相关性。联合国艾滋病规划署（UNAIDS） 促进高水平（90%或更高）的艾滋病毒诊断、抗逆转录病毒治疗覆盖率， 病毒学抑制（“90-90-90”目标），以结束艾滋病毒的流行。然而，尽管几乎满足这些 在博茨瓦纳，我们观察到艾滋病毒年发病率> 1%。此外，超过15%的成年人 博茨瓦纳人口的抗逆转录病毒治疗（以及最近普遍抗逆转录病毒治疗的实施），我们必须 了解广泛治疗对临床结果和非传染性疾病的影响 艾滋病毒感染者的发病率。因此，我们将：a） 将成人的特征描述为 使用预测分析确定最近感染艾滋病毒的人群，以确定感染艾滋病毒的最高风险群体 在当前的疫情中，并通过对最近的个人深入采访来增加我们的理解- B）研究TDF/FTC预处理靶向方法的可行性、可接受性和吸收率， 向符合这一高风险特征的艾滋病毒阴性者提供接触预防; HIV（和早期ART）对临床结果的影响，包括 癌症发病率与高血压 感染艾滋病毒的成人与未感染艾滋病毒的成人的流行率，以及 开始接受艾滋病毒治疗者的艾滋病毒相关结果 dolutegravir与efavirenz为基础的ART。 此外，洛克曼博士还将指导初级研究人员， 在一项新的大型随机IMPAACT试验中嵌套的项目，该试验在妊娠期使用3种抗逆转录病毒治疗方案 她领导的研究，以及之前在博茨瓦纳进行的大型围产期艾滋病毒研究， 母婴配对这一K24至关重要，它可以支持所需的受保护时间和资源， 博士洛克曼将指导来自美国和博茨瓦纳的初级调查人员 病人导向的研究。