Conduct of Studies to Evaluate the Cardiovascular Toxicity of an HIV Tricombo Therapy (ABC/DTG/3TC) ing Sprague Dawley Rats (F0 Dosed by Oral Gavage; F1 Exposed Perinatally)

对 Sprague Dawley 大鼠进行 HIV Tricombo 疗法 (ABC/DTG/3TC) 心血管毒性的研究（F0 口服灌胃给药；F1 围产期暴露）

• 批准号: 10788076
• 负责人: Barney Sparrow
• 金额: $ 216.42万
• 依托单位: BATTELLE MEMORIAL INSTITU
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2023-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10788076
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Adverse effects; Animals; Cardiac; Cardiotoxicity; Cardiovascular system; Chemicals; Chronic; Dose; Evaluation; Exposure to; Goals; HIV; HIV Seropositivity; HIV/AIDS; Individual; Lactation; Lamivudine; Oral; Perinatal Exposure; Pregnancy; Pregnant Women; Recommendation; Sprague-Dawley Rats; Syndrome; Time; Toxic effect; Toxicology; Virus Diseases; Weaning; abacavir; antiretroviral therapy; design; disorder prevention; early life exposure; offspring; programs

The goal of this project is to provide support of the Division of Translational Toxicology (DTT) activities targeted toward the prevention of diseases or adverse effects caused by exposure to chemical or physical agents. This program is designed to evaluate toxicity following early life exposure to chemicals. Antiretroviral therapies (ART) are recommended for all HIV positive individuals including pregnant mothers. Abacavir (ABC) /dolutegravir (DTG)/lamivudine (3TC) is an ART under evaluation in the project with a specific focus on potential cardiovascular toxicity in F0 dams dosed daily with ABC/DTG/3TC from gestation day 6 through weaning of their F1 offspring, and for an additional 3 months. F1 offspring will be exposed perinatally (gestation and lactational transfer) but not directly dosed. Both F1 and F0 animals will be evaluated at several time points for functional cardiac parameters to determine if ABC/DTG/3TC exposure induces cardiotoxicity. Keywords: HIV/AIDS, Human immunodeficiency virus infection, acquired immune deficiency syndrome, primary HIV, acute retroviral syndrome, asymptomatic HIV, chronic HIV

本项目的目标是为转化毒理学（DTT）部门的活动提供支持，这些活动旨在预防因接触化学或物理制剂而引起的疾病或不良反应。该计划旨在评估早期接触化学品后的毒性。抗逆转录病毒疗法（ART）建议所有艾滋病毒阳性的个人，包括孕妇。阿巴卡韦（ABC）/度鲁特韦（DTG）/拉米夫定（3 TC）是该项目中正在评价的一种ART，特别关注从妊娠第6天至F1代后代断奶期间每天给予ABC/DTG/3 TC的F0代母鼠的潜在心血管毒性，并持续额外3个月。F1代子代将在围产期暴露（妊娠和哺乳期转移），但不直接给药。将在几个时间点评价F1和F0代动物的功能性心脏参数，以确定ABC/DTG/3 TC暴露是否诱导心脏毒性。 保留字：艾滋病毒/艾滋病、人体免疫缺陷病毒感染、获得性免疫缺陷综合征、原发性艾滋病毒、急性逆转录病毒综合征、无症状艾滋病毒、慢性艾滋病毒