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; 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

该项目的目的是提供针对预防疾病或因化学物质或物理剂引起的疾病或不良影响的转化毒理学（DTT）活动的支持。该计划旨在评估早期寿命暴露于化学物质后的毒性。建议所有HIV阳性个体（包括怀孕母亲）抗逆转录病毒疗法（ART）。 Abacavir（ABC）/Dolutegravir（DTG）/Lamivudine（3TC）是该项目中的一种正在评估的艺术，特别关注每天用ABC/DTG/DTG/3TC服用的F0大坝潜在的心血管毒性，从Gestation Days开始，从妊娠第6天开始通过f1 fors for f1 fors for for for for for for for for for for for for for for for。 F1后代将围产期暴露（妊娠和泌乳转移），但不直接剂量。 F1和F0动物都将在功能性心脏参数的几个时间点进行评估，以确定ABC/DTG/3TC暴露是否诱导心脏毒性。 关键词：艾滋病毒/艾滋病，人类免疫缺陷病毒感染，获得的免疫缺陷综合征，原发性HIV，急性逆转录病毒综合征，无症状HIV，慢性HIV