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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 主要目标 1.评估两种单一疗法(替诺福韦(TDF)单独与阿巴卡韦(ABC))与TDF ABC双重NRTI方案的相对效力，通过短期病毒学反应(I期病毒衰变的斜率和第7天HIV RNA的变化)进行评估。 2.比较两种单用药方案与双NRTI方案的血浆和细胞内PK数据。 次要目标 1.通过RT-PCR检测TDF-ABC暴露21天后细胞内核苷类似物跨细胞膜转运相关调节酶的变化。 2.确定单用ABC或TDF治疗7天后或联合应用ABC TDF治疗7天后是否出现NRTI相关突变。 3.比较TDF单药与ABC单药的相对病毒效力。 4.评价Efavirenz(EFV)ABC 3TC在两个为期7天的单一/双重治疗序列后的长期病毒应答。 5.评价两种单一治疗方案的相对毒性。

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.