Rapid Turnover of 2-LTR HIV-1 DNA during Early Stage of Highly Active Antiretroviral Therapy 英文参考文献.docVIP

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Rapid Turnover of 2-LTR HIV-1 DNA during Early Stage of Highly Active Antiretroviral Therapy 英文参考文献.doc

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Rapid Turnover of 2-LTR HIV-1 DNA during Early Stage of Highly Active Antiretroviral Therapy 英文参考文献

RapidTurnoverof2-LTRHIV-1DNAduringEarlyStageof HighlyActiveAntiretroviralTherapy WeijunZhu1.,YanmeiJiao2.,RongyueLei1,WeiHua2,RuiWang2,YunxiaJi2,ZhiyingLiu2,FeiliWei2, TongZhang2,XuanlinShi3,HaoWu2*,LinqiZhang1,3* 1AIDSResearchCenter,InstituteofPathogenBiology,ChineseAcademyofMedicalSciencesandPekingUnionMedicalCollege,Beijing,China,2CenterforInfectious Diseases, BeijingYou-AnHospital,CapitalMedicalUniversity,Beijing, China, 3ComprehensiveAIDSResearchCenterandResearchCenterfor PublicHealth,School of Medicine,TsinghuaUniversity,Beijing,China Abstract Background:Despiteprolongedtreatmentwithhighlyactiveantiretroviraltherapy(HAART),theinfectiousHIV-1continues toreplicateandresideslatentlyintherestingmemoryCD4+Tlymphocytes,whichblockstheeradicationofHIV-1.Theviral persistence of HIV-1 is mainly caused by its proviral DNA being either linear nonintegrated, circular nonintegrated, or integrated.PreviousreportshavelargelyfocusedonthedynamicsofHIV-1DNAfromthesamplescollectedwithrelatively long time intervals during the process of disease and HAART treatment, which may have missed the intricate changes duringtheintervalsinearlytreatment. Methodology/Principal Findings: In this study, we investigated the dynamics of HIV-1 DNA in patients during the early phaseofHARRTtreatment.UsingoptimizedrealtimePCR,weobservedsignificantchangesin2-LTRduringthefirst12- weekoftreatment,whiletotalandintegratedHIV-1DNAremainedstable.Thedoublingtimeandhalf-lifeof2-LTRwerenot correlatedwiththebaselineandtherateofchangesinplasmaviralloadandvariousCD4+T-cellpopulations.Longitudinal analyseson2-LTRsequencesandplasmalipopolysaccharide(LPS)levelsdidnotrevealanysignificantchangesinthesame treatmentperiod. Conclusions/Significance: Our study revealed the rapid changes in 2-LTR concentration in a relatively large number of patientsduringtheearlyHAARTtreatment.Therapidchangesindicatetherapidinfusionandclearanceofcellsbearing2- LTRintheperipheralblood.Thosechangesarenotexpectedtobecausedbytheblock