Antiretroviral Therapy Strategies to Lower Cancer Risk in HIV-Infected Persons

降低艾滋病毒感染者患癌症风险的抗逆转录病毒治疗策略

• 批准号: 8545747
• 负责人: ROBERT D DUBROW
• 金额: $ 57.09万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-14 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545747
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Alcohol consumption; American; Anal Melanoma; Biological Preservation; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Canada; Caring; Cell Count; Clinical; Collaborations; Colorectal; Consequences of HIV; Data; Etiology; General Population; Goals; HIV; Hodgkin Disease; Human Papillomavirus; Immunologic Deficiency Syndromes; Immunosuppression; Incidence; Individual; Infection; Inflammation; Kaposi Sarcoma; Liver; Longevity; Lung; Malignant Neoplasms; Malignant neoplasm of pharynx; Measures; Mediating; Methodology; Morbidity - disease rate; Non-Hodgkin' s Lymphoma; Oral cavity; Outcome; Patients; Pattern; Persons; Pharmaceutical Preparations; Population; Prostate; RNA; Randomized Controlled Trials; Regimen; Research; Research Design; Research Personnel; Risk; Risk Factors; Risk Reduction; Sample Size; Sampling; Second Primary Cancers; Smoking; Structural Models; Structure; Time; United States; Viral; Virus; Virus Replication; antiretroviral therapy; base; cancer diagnosis; cancer risk; cancer type; cohort; comparative effectiveness; evidence based guidelines; follow-up; immune function; mortality; multidisciplinary; primary outcome; public health relevance; secondary outcome; virus related cancer

DESCRIPTION (provided by applicant): "When to start" antiretroviral therapy (ART) and "what to start" represent key ongoing issues in HIV care. While these questions have been asked for the outcomes of AIDS and all-cause mortality, they now need to be extended to other serious outcomes, including cancer, which has endured as a major cause of morbidity and mortality for HIV-infected patients. The overarching goal of the current proposal is to formulate evidence-based recommendations about the preferred CD4 T-cell count at which to initiate ART, and the preferred initial ART regimen, that would minimize cancer incidence among HIV-infected persons. We will conduct this research within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), which includes 22 diverse HIV cohorts in the U.S. and Canada with more than 100,000 HIV-infected patients, validated cancer diagnoses, and up to 15 years of follow-up. We will focus on three cancer groups as primary outcomes: AIDS- defining cancers, virus-related non-AIDS-defining cancers (NADC), and virus-unrelated NADC. We propose these grouped primary endpoints because their large Ns provide good statistical power and because clinical decisions about when and what to start might be based more on effects on cancer incidence for aggregated related cancers than on effects on incidence of individual cancer types. We also will consider 14 specific cancer types/groups as secondary outcomes. We propose to achieve two complementary and interrelated specific aims. The first aim will use a restricted sample of NA-ACCORD to emulate randomized controlled trials of ART for reducing cancer risk using causal statistical methodologies. This aim will evaluate the effect of the timing and composition of the initial ART regimen on the incidence of our primary and secondary cancer outcomes and includes two sub-aims: Aim 1a will evaluate whether initiation of ART at higher CD4 thresholds is associated with reduced incidence compared with initiation of ART at lower CD4 thresholds; Aim 1b will determine whether cancer incidence varies for the major ART classes and more common individual ART medications. The second aim will use the entire NA-ACCORD sample to elucidate the underlying relationships between patterns of immune suppression, HIV virus replication and incidence of our primary and secondary cancer outcomes and also has two sub-aims: Aim 2a will examine relationships between cancer risk and cumulative and current CD4 count and HIV RNA; Aim 2b will evaluate whether ART use, specific ART classes, or more common individual ART medications have an effect on cancer risk independent of the effect mediated by measures of CD4 count and HIV RNA found to be key predictors of cancer risk in Aim 2a. NA-ACCORD provides an ideal platform for conducting this study, with its diverse cohorts, large sample size, validated cancer diagnoses, longitudinal data on CD4 count, HIV RNA, and ART use, data on traditional cancer risk factors, efficient structure for harmonization of data, and high level of multidisciplinary expertise of collaborating investigators.

描述（由申请人提供）：“何时开始”抗逆转录病毒疗法（ART）和“什么开始”代表艾滋病毒护理中的关键问题。尽管这些问题已被要求取得艾滋病和全因死亡率的结果，但现在需要将它们扩展到其他严重的结果，包括癌症，癌症已忍受了艾滋病毒感染患者的发病率和死亡率的主要原因。当前提案的总体目标是制定有关首选CD4 T细胞计数的基于证据的建议，该建议可以在其中启动艺术，而首选的初始艺术方案将最大程度地减少感染HIV感染者的癌症发病率。我们将在北美艾滋病研究与设计方面的北美艾滋病队列合作（NA-Accord）中进行这项研究，该合作包括美国和加拿大的22种不同的艾滋病毒队列，其中有100,000多名HIV感染的患者，经过验证的癌症诊断，并进行了15年的随访。我们将专注于三个癌症组作为主要结果：定义癌症，与病毒相关的非辅助癌症（NADC）和与病毒无关的NADC。我们提出了这些分组的主要终点，因为它们的大NS提供了良好的统计能力，并且因为何时和开始的临床决策可能更多地基于对癌症相关癌症的影响而不是对单个癌症类型发生率的影响的影响。我们还将将14种特定的癌症类型/组视为次要结果。我们建议实现两个互补和相互关联的特定目标。第一个目标将使用受限制的NA-Accord样本模仿ART的随机对照试验，以使用因果统计方法来降低癌症风险。该目标将评估初始艺术方案的时间和组成对我们初级和继发性癌症结果的发生率的影响，并包括两个子IAM：AIM 1A将评估在较高CD4阈值下以较​​高的CD4阈值的启动与与低CD4阈值的ART启动相比，与降低的ART阈值相关； AIM 1B将确定主要艺术类别和更常见的个人艺术药物的癌症发生率是否有所不同。第二个目的将使用整个NA-ACORD样本来阐明免疫抑制，HIV病毒复制模式与我们的原发性和继发性癌症结果的发生之间的潜在关系，并且还具有两个子-IAM：AIM 2A将研究癌症风险与累积的和累积的CD4计数和当前CD4计数和HIV RNA之间的关系； AIM 2B将评估艺术使用，特定的艺术类别或更常见的个人艺术药物是否对癌症风险产生影响，而不是由CD4计数和HIV RNA介导的效果，发现是AIM 2A中癌症风险的关键预测指标。 NA-Accord提供了进行这项研究的理想平台，其队列多样，样本量，经过验证的癌症诊断，CD4计数，HIV RNA和ART使用的纵向数据，传统癌症风险因素的数据，有效的数据协调结构以及高水平的多学科协作专业知识 调查人员。