VIRAL DYNAMICS AND PHARMACOKINETICS OF TDF AND ABC MONOTHERAPY VERSUS THE COMB

TDF 和 ABC 单疗法与梳子疗法的病毒动力学和药代动力学

• 批准号: 7725003
• 负责人: CATHERINE A DIAMOND
• 金额: $ 3.7万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725003
• 关键词: Cell membrane; Comb animal structure; Computer Retrieval of Information on Scientific Projects Database; Data; Drug Kinetics; Enzymes; Funding; Grant; HIV; Institution; Lamivudine; Messenger RNA; Mono-S; Mutation; Phase; RNA; Relative (related person); Research; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Source; Tenofovir; Toxic effect; Transcript; Treatment Protocols; United States National Institutes of Health; Viral; abacavir; day; efavirenz; nucleoside analog; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Primary Objectives 1. To evaluate the relative potencies of two monotherapy regimens (Tenofovir(TDF) alone vs. Abacavir(ABC) alone) compared to a dual NRTI regimen of TDF + ABC as assessed by the short-term virologic response (slope of the phase I viral decay and change in HIV RNA at day 7). 2. To compare the plasma and intracellular PK data of the two monotherapy regimens compared to the dual NRTI regimen. Secondary Objectives 1. To evaluate the change in cellular regulatory enzymes involved with nucleoside analogue transport across cell membranes as assessed by RT-PCR of specific mRNA transcripts after 21 days of TDF+ABC exposure. 2. To determine if NRTI-associated mutations emerge after 7 days of ABC or TDF monotherapy or after 7 days of dual NRTI therapy with ABC + TDF. 3. To compare the relative viral potency of TDF monotherapy versus ABC monotherapy. 4. To evaluate the long-term viral response to Efavirenz (EFV) + ABC + 3TC after two 7-day sequences of mono/dual-therapy. 5. To evaluate the relative toxicities of the two monotherapy treatment regimens.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 主要目标 1. 通过短期病毒学应答（第7天I期病毒衰减的斜率和HIV RNA的变化）评估两种单药治疗方案（替诺福韦（TDF）单药vs阿巴卡韦（ABC）单药）与TDF + ABC双重NRTI方案相比的相对效力。 2. 比较两种单药治疗方案与双联NRTI方案的血浆和细胞内PK数据。 次要目的 1. 评价TDF+ABC暴露21天后，通过特定mRNA转录物的RT-PCR评估的参与核苷类似物跨细胞膜转运的细胞调节酶的变化。 2. 确定ABC或TDF单药治疗7天后或ABC + TDF双重NRTI治疗7天后是否出现NRTI相关突变。 3. 比较TDF单药治疗与ABC单药治疗的相对病毒效力。 4. 评价两个7天单药/双联治疗序列后对依法韦仑（EFV）+ ABC +3 TC的长期病毒应答。 5. 评价两种单药治疗方案的相对毒性。