Acceptability and feasibility of combination treatment for cervical precancer among South Africa women living with HIV

南非艾滋病毒感染者宫颈癌前病变联合治疗的可接受性和可行性

基本信息

批准号：
10165676
负责人：
Carla J Chibwesha
金额：
$ 47.29万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10165676
关键词：
Ablation Accounting Address Adherence Adjuvant African Aftercare Area Biopsy Cervical Cervical Cancer Screening Cervical Intraepithelial Neoplasia Cessation of life Community Health Education Disease Dose Education and Outreach Enrollment Excision Fluorouracil Focus Groups Frequencies Generations Generic Drugs Genital Genitalia Genotype Goals HIV HIV-1 Health Health Personnel High Risk Woman Histology Human Papilloma Virus Vaccination Human Papillomavirus Immune Immune response Incidence Inflammation Infrastructure Interleukin-1 alpha Interleukin-10 Interleukin-12 Interview Investments Irrigation Malignant Neoplasms Malignant neoplasm of cervix uteri Measures Mediating Modality Nurses Operative Surgical Procedures Outcome Participant Patients Perception Placebos Population Prevention strategy RNA Randomized Recurrence Reporting Research Resources Risk Rural Safety Self Administration Series Sexually Transmitted Diseases South Africa South African Specimen TNF gene Testing Treatment outcome Woman acceptability and feasibility cancer prevention cancer therapy cervical cancer prevention cervicovaginal cost cytokine efficacy study efficacy testing experience feasibility trial high risk population immune activation improved lifetime risk loop electrosurgical excision procedure low and middle-income countries male mortality disparity novel premalignant prevent primary outcome screening secondary outcome standard care treatment strategy tumor-immune system interactions

项目摘要

ABSTRACT Cancer incidence, mortality, and disparities between rich and poor are projected to rise at staggering rates. It is estimated, for example, that cancer will kill one million Africans each year by 2030, with cervical cancer accounting for the most cancer deaths in African women. Global efforts to eliminate cervical cancer are currently focused on expanding access to HPV vaccination and cervical cancer screening. However, these efforts lack equal investment in treatment of precancerous cervical intraepithelial neoplasia grade 2/3 (CIN2/3), particularly among HIV-infected women. This gap leaves a generation of HIV-infected women at high risk of persistent/recurrent CIN2/3 and progression to cervical cancer because standard treatment for CIN2/3 (excision or ablation) is far less effective in this population. The need for novel treatment approaches for CIN2/3 in HIV- infected women is therefore substantial. The central hypothesis of our proposal is that topical 5-fluorouracil (5FU), a widely available low-cost generic drug, can be repurposed as a patient-controlled, adjuvant treatment for CIN2/3 after surgical excision to reduce the risk of persistent/recurrent CIN2/3 and progression to cervical cancer among HIV-infected women. Our overarching goal is to build on U.S. efficacy studies and test the acceptability and feasibility of combination treatment for CIN2/3 (i.e., surgical excision followed by self- applied adjuvant 5FU) in a low-resource setting. First, we will explore South African perspectives on current cervical cancer prevention strategies and identify barriers to and facilitators of combination treatment in the local context. We will accomplish this through a series of focus groups and in-depth interviews with diverse stakeholders (HIV-infected women, male partners, healthcare personnel). Second, and informed by our formative research, we will conduct a feasibility trial of the combination treatment strategy to determine safety, tolerability, adherence, and retention. We will randomize 180 HIV-infected women with CIN2/3 who will undergo loop excision (LEEP) followed by self-apply 5FU versus placebo (8 doses, once every 2 weeks). Women will be followed for 24 weeks. Third, to better understand the immune response to combination treatment in HIV-infected women, we will assess changes in genital HIV-1 shedding and local immune activation associated with surgical excision followed by 5FU/placebo. Our study will be conducted in South Africa, where more than 4 million women are living with HIV and women’s lifetime risk of cervical cancer is among the highest in the world. If successful, our findings will have broad relevance for HIV-infected women in both resource-rich and resource-poor regions worldwide, including rural and remote areas of the U.S.

抽象的癌症事件，死亡率和贫富之间的差异预计会以惊人的速度上升。这是例如，据估计，到2030年，癌症每年将杀死一百万的非洲人，宫颈癌占非洲妇女癌症死亡最多的原因。目前，全球消除宫颈癌的努力是专注于扩大接受HPV疫苗接种和宫颈癌筛查的机会。但是，这些努力缺乏在治疗癌前颈上皮内肿瘤2/3级（CIN2/3）方面的平等投资，特别是在感染艾滋病毒的妇女中。这一差距使一代人感染了艾滋病毒的妇女由于CIN2/3的标准治疗或消融）在这个人群中的效率远不如。 HIV中CIN2/3的新型治疗方法的需求因此，受感染的妇女很重要。我们提议的中心假设是局部5-氟尿嘧啶（5FU）是一种可用的低成本通用药物，可以重新使用为患者控制，调整治疗对于CIN2/3，手术后的惊喜降低了持续/复发CIN2/3的风险并发展为宫颈艾滋病毒感染的妇女中的癌症。我们的总体目标是建立美国效率研究并测试 CIN2/3组合治疗的可接受性和可行性（即手术切除，然后是自我在低资源设置中施加调整5FU）。首先，我们将探讨南非有关当前的观点宫颈癌预防策略并确定当地治疗中联合治疗的障碍和促进者语境。我们将通过一系列焦点小组和对潜水员的深入访谈来实现这一目标利益相关者（受艾滋病毒感染的妇女，男性伴侣，医疗保健人员）。第二，并由我们的信息形成性研究，我们将对组合治疗策略进行可行性试验，以确定安全性，耐受性，依从性和保留性。我们将随机分配180名CIN2/3的HIV感染妇女循环切除（LEEP），然后是自动5FU与安慰剂（8剂，每2周一次）。女人会紧随其后的是24周。第三，以更好地了解HIV感染的联合治疗的免疫反应妇女，我们将评估生殖器HIV-1脱落和与手术相关的局部免疫激活的变化切除，然后是5FU/安慰剂。我们的研究将在南非进行，超过400万妇女世界上有艾滋病毒和妇女的终生风险是世界上最高的。如果成功，我们的发现将与资源丰富和资源贫乏地区的艾滋病毒感染的妇女具有广泛的意义全球，包括美国的粗糙和偏远地区