Role of Connection and RNase H Domains of HIV-1 RT in Antiviral Drug Resistance

CN和RH突变在非B亚型抗病毒耐药性中的作用尚不清楚。我们将鉴定C亚型和CRF01_AE的CN和RH突变，并确定它们对NRTIs和NNRTIs耐药性的影响。我们将对使用NNRTI治疗失败的患者进行分型，以确定CN和RH突变的存在是否可以预测含AZT的抢救治疗失败率更高。我们将表征与耐药性相关的CN突变对病毒适合性的影响。我们将在存在和不存在抗病毒药物的情况下，使用竞争分析来确定与耐药性相关的CN突变对病毒适合性的影响。我们将剖析导致CN和RH遗传变异的机制。[对应于2007年4月艾滋病毒耐药计划现场访问报告中的Pathak项目2]

The role of CN and RH mutations in conferring antiviral drug resistance in non-B subtypes is poorly defined. We will characterize CN and RH mutations in subtype C and CRF01_AE and determine their impact on resistance to NRTIs and NNRTIs. We will genotype patients who are failing a regimen containing NNRTI therapy to determine whether the presence of CN and RH mutations can predict a higher rate of failure to AZT-containing salvage therapy. We will characterize the effects of CN mutations associated with drug resistance on viral fitness. We will determine the impact of CN mutations associated with drug resistance on viral fitness using competition assays in the presence and absence of antiviral drugs. We will dissect the mechanisms that contribute to genetic variation in CN and RH. [Corresponds to Pathak Project 2 in the April 2007 site visit report of the HIV Drug Resistance Program]