ORIGIN AND EVOLUTION OF HIV-1 DRUG RESISTANCE

HIV-1 耐药性的起源和演变

• 批准号: 8357636
• 负责人: Shiu-Lok Hu
• 金额: $ 37.79万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357636
• 关键词: Affect; Animals; Anti-Retroviral Agents; Blood; Blood specimen; Drug resistance; Evolution; Family suidae; Funding; Grant; HIV-1; Individual; Infection; Macaca; Measures; Modeling; Mutation; National Center for Research Resources; Pharmaceutical Preparations; Primates; Principal Investigator; Research; Research Infrastructure; Resistance; Resources; Site; Source; Tail; Tissues; United States National Institutes of Health; Viral; Viremia; Virus; antiretroviral therapy; cost; drug resistant virus; efavirenz; in vivo; non-nucleoside reverse transcriptase inhibitors; nucleoside analog; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Drug resistance is a significant issue affecting the treatment options of individuals infected with HIV-1. Some drug resistance-conferring mutations can persist for long periods in the host and can be transmitted horizontally and/or vertically to new individuals. How drug resistance-conferring mutations arise during treatment, particularly in anatomical sites other than the blood, is not understood and may affect transmission of drug resistant HIV-1 and persistence of viral reservoirs throughout the body. To date, no studies have longitudinally sampled blood and different anatomical compartments to identify the origins and emergence of drug resistant isolates and to measure antiretroviral drug concentrations at those same sites. In this subcontract, we propose to use a RT-SHIVmne infection model in pig-tailed macaques to study the origin and evolution of HIV-1 drug resistance. The Specific Aims of this project are: (1): To examine longitudinally the emergence of drug resistance-conferring mutations in RT that arise in RT-SHIVmne-infected macaques receiving monotherapy with the nucleoside analog FTC , or the non-nucleoside RT inhibitor efavirenz, in blood and different anatomical compartments; (2): To determine the tissue origin of the re-emergence of wild-type virus and/or persistence of drug resistant virus after discontinuation of monotherapy and after suppression of viremia with combination antiretroviral therapy in the RT-SHIVmne-infected animals; (3): To measure the concentration of antiretroviral drugs in the blood and tissue compartments of RT-SHIVmne-infected macaques described above and correlate these with emergence of resistance. In vivo studies in Specific Aim 1 were initiated in January of 2011.

这个子项目是利用这些资源的众多研究子项目之一