Clinical Relevance of Transient Nevirapine Resistance

奈韦拉平短暂耐药的临床相关性

• 批准号: 6843382
• 负责人: Louise Kuhn
• 金额: $ 52.48万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6843382
• 关键词: AIDS therapy; African; HIV infections; clinical research; drug adverse effect; drug resistance; female; gene mutation; human immunodeficiency virus 1; human pregnant subject; human subject; human therapy evaluation; nevirapine; newborn human (0-6 weeks); outcomes research; patient oriented research; pediatric AIDS; vertical transmission; virus genetics; virus load

DESCRIPTION (provided by applicant): Nevirapine (NVP) is a simple, effective and relatively safe antiretroviral drug now widely used in low resource settings around the world to prevent mother-to-child transmission of HIV. NVP is also a useful drug to use as part of treatment regimens. Concern has been raised that exposure to this drug for prevention may compromise its use in treatment. The concern has arisen because viral mutations which confer resistance to NVP appear to be common among HIV-infected women and children after exposure to even single dose NVP. A study is proposed to test whether or not exposure to NVP for prevention of mother-to-child HIV transmission, and the resulting NVP resistance mutations associated with its use, will adversely influence response to a subsequent treatment regimen which includes NVP. The study will recruit HIV-infected women and their children, NVP-exposed and unexposed, in Johannesburg, South Africa, who meet criteria for starting antiretroviral treatment and will start them on a treatment regimen which includes NVP. HIVinfected women and children exposed to NVP prophylaxis will be compared to similar unexposed women and children. Further, among those exposed to NVP prophylaxis, those with NVP resistance mutations at 6 weeks post-NVP exposure will be compared to those exposed to NVP but who do not have detectable mutations. The primary study outcome is treatment failure defined on the basis of virologic outcomes at 6 months after starting treatment. Secondary objectives of the study are to characterize the nature of viral resistance mutations associated with NVP prophylaxis (including the specific mutations present, their occurrence in plasma and/or PBMCs, their frequency if the threshold of detection is lowered to detect mutations present at low frequencies in the viral population) and to investigate whether these characteristics of viral resistance explain treatment failure. The study will generate empirical data essential for formulation of evidence-based treatment policies for the hundreds of thousands of HIV-infected women and children living in low resource settings who are likely to have had prior exposure to NVP.

描述（申请人提供）：奈韦拉平（NVP）是一种简单、有效且相对安全的抗逆转录病毒药物，目前在世界各地资源匮乏的地区广泛用于预防艾滋病毒母婴传播。 NVP 也是一种有用的药物，可用作治疗方案的一部分。人们担心，为了预防而接触这种药物可能会影响其在治疗中的使用。人们之所以引起人们的关注，是因为在感染艾滋病毒的妇女和儿童中，即使接触单剂量 NVP 后，导致对 NVP 产生耐药性的病毒突变似乎也很常见。拟开展一项研究，测试暴露于 NVP 来预防 HIV 母婴传播，以及与其使用相关的 NVP 耐药性突变是否会对后续包含 NVP 的治疗方案的反应产生不利影响。该研究将在南非约翰内斯堡招募符合开始抗逆转录病毒治疗标准的感染艾滋病毒的妇女及其子女，包括接触过 NVP 和未接触过 NVP 的妇女及其子女，并将开始对她们进行包括 NVP 在内的治疗方案。接受 NVP 预防的 HIV 感染妇女和儿童将与未接受 NVP 预防的类似妇女和儿童进行比较。此外，在那些接受 NVP 预防的患者中，那些在 NVP 暴露后 6 周出现 NVP 耐药突变的患者将与那些暴露于 NVP 但没有可检测到的突变的患者进行比较。主要研究结果是根据开始治疗后 6 个月的病毒学结果定义的治疗失败。该研究的次要目标是表征与 NVP 预防相关的病毒耐药突变的性质（包括存在的特定突变、它们在血浆和/或 PBMC 中的发生情况、如果降低检测阈值以检测低频率存在的突变，则它们的频率）病毒群体中）并调查这些病毒耐药性特征是否可以解释治疗失败。该研究将为生活在资源匮乏地区的数十万艾滋病毒感染妇女和儿童（可能之前接触过 NVP）制定循证治疗政策提供重要的经验数据。