Prevention of HIV resistance to nevirapine in pregnancy

妊娠期预防艾滋病毒对奈韦拉平的耐药性

• 批准号: 6408825
• 负责人: Lisa M Frenkel
• 金额: $ 4.38万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6408825
• 关键词: HIV infections; Peru; antiviral agents; birth; chemoprevention; clinical research; clinical trials; combination chemotherapy; cooperative study; drug resistance; gene mutation; health care cost /financing; human immunodeficiency virus 1; human pregnant subject; human subject; human therapy evaluation; infant human (0-1 year); lamivudine; microorganism disease chemotherapy; nevirapine; pediatric AIDS; postpartum; pregnancy circulation; vertical transmission; virus genetics; zidovudine

DESCRIPTION (provided by applicant): This research will be done primarily in Peru as an extension of NIH grant #5 R0l HD36184. Widespread use of nevirapine chemoprophylaxis has been implemented to achieve moderately effective reduction of peripartum HIV- 1 transmission at a relatively low cost. Nevirapine, however, rapidly selects for drug resistant HIV- 1 as only a single base mutation, either K103N or Y181C, confer high-level resistance. Not surprisingly, HIV-l resistant to nevirapine has been detected in the plasma of women six weeks following a single dose of nevirapine. As a result of political and humanitarian efforts, the costs of certain antiretroviral medications have been markedly reduced. As systems are developed to provide therapy to economically disadvantaged populations, antiretroviral therapy will become more available for treatment of an increasing number of infected individuals. The increased availability of therapy for women in the near future warrants the use of chemoprophylactic regimens in pregnancy and during labor that will not compromise the effectiveness of future antiretroviral therapy by the selection of resistant virus. The proposed project will quantify the proportion of nevirapine resistant virus in the quasispecies of women of who receive single dose nevirapine for peripartum chemoprophylaxis of their infant, and defme its persistence and kinetics for six months postpartum. We also propose to detennine if co-administration of zidovudine and lamivudine (Combivir) for one week postpartum following the administration of nevirapine can prevent the selection of virus resistant to all three antiretrovirals. Lastly, we propose to transfer laboratory assays relevant to the investigation of mother-to-infant HIV-1 transmission and trials of antiretroviral therapy to investigators in Lima, Peru. A sensitive, simple and economical assay for early diagnosis of HIV- 1 in infants and a sensitive and economical oligo-ligase assay (OLA) that we have adapted to test for HIV-l resistance mutations will be transferred, including equipment and teaching of personnel. This proposal is an effort of further our commitment to the development of a research program in Peru that addresses issues pertinent to perinatal HIV-1l transmission, and to train and assist Peruvians investigators in this research.

描述（由申请人提供）：这项研究将主要在 秘鲁作为 NIH 拨款 #5 R0l HD36184 的延伸。奈韦拉平的广泛使用 已实施化学预防以实现适度有效的减少 以相对较低的成本减少围产期 HIV-1 传播。奈韦拉平， 然而，快速选择耐药 HIV-1 仅作为单一碱基 突变（K103N 或 Y181C）赋予高水平的抗性。不是 令人惊讶的是，在血浆中检测到了对奈韦拉平具有耐药性的 HIV-1。 女性服用单剂量奈韦拉平六周后。由于政治原因 和人道主义努力，某些抗逆转录病毒药物的费用已经 已明显减少。随着系统的发展来提供治疗 经济弱势群体，抗逆转录病毒治疗将变得更加重要 可用于治疗越来越多的感染者。这 在不久的将来，女性获得更多治疗的机会值得使用 怀孕和分娩期间的化学预防方案不会 通过选择损害未来抗逆转录病毒治疗的有效性 的耐药病毒。 拟议项目将量化奈韦拉平耐药病毒的比例 在接受单剂​​量奈韦拉平治疗的准种女性中 婴儿的围产期化学预防，并确定其持续性和 产后六个月的动力学。我们还建议确定是否 齐多夫定和拉米夫定（Combivir）联合给药一周 产后服用奈韦拉平可以防止选择 病毒对所有三种抗逆转录病毒药物均具有抗药性。最后，我们建议转移 与母婴 HIV-1 调查相关的实验室检测 向利马的研究人员传播抗逆转录病毒疗法并进行试验， 秘鲁。一种灵敏、简单且经济的检测方法，用于早期诊断 HIV-1 婴儿和我们拥有的灵敏且经济的寡连接酶测定 (OLA) 用于测试 HIV-1 耐药突变的适应性将被转移，包括 设备和人员教学。 该提案是我们进一步致力于发展 秘鲁解决围产期 HIV-1l 相关问题的研究计划 传播，并培训和协助秘鲁调查人员进行这项研究。