Emergency of Primary NNRTI Resistance Mutations without Antiretroviral Selective Pressure in a HAART-Treated Child 英文参考文献.docVIP

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Emergency of Primary NNRTI Resistance Mutations without Antiretroviral Selective Pressure in a HAART-Treated Child 英文参考文献.doc

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Emergency of Primary NNRTI Resistance Mutations without Antiretroviral Selective Pressure in a HAART-Treated Child 英文参考文献

EmergencyofPrimaryNNRTIResistanceMutations withoutAntiretroviralSelectivePressureinaHAART- TreatedChild ElizabethS.Machado1,2,AdrianaO.Afonso2,DwightV.Nissley3,4,PhilippeLemey5¤,SilviaM.Cunha6, RicardoH.Oliveira6,MarceloA.Soares2,7* 1HospitalUniversita′rio ClementinoFragaFilho,UniversidadeFederaldoRiodeJaneiro,RiodeJaneiro,Brazil,2DepartamentodeGene′tica,UniversidadeFederaldoRio deJaneiro,RiodeJaneiro,Brazil,3GeneRegulationandChromosomeBiologyLaboratory,NCI-Fredrick,Frederick,Maryland,UnitedStatesofAmerica,4BasicScience Program, SAIC-Frederick, Inc., NCI-Fredrick, Frederick, Maryland, United States of America, 5Department of Zoology, Oxford University, Oxford, United Kingdom, 6InstitutodePuericulturaePediatriaMartaga?oGesteira,UniversidadeFederaldoRiodeJaneiro,RiodeJaneiro,Brazil,7Divisa?odeGene′tica,InstitutoNacionaldeCa?ncer, RiodeJaneiro,Brazil Abstract Objective: The use of antiretrovirals (ARV) during pregnancy has drastically reduced the rate of the human immunodeficiency virus perinatal transmission (MTCT). As a consequence of widespread ARV use, transmission of drug resistantstrainsfrommotherstotheirbabiesisincreasing.Ultra-sensitivePCRtechniqueshavepermittedthequantification ofminorityviralpopulations,butlittleisknownaboutthetransmissionofdrug-resistantHIV-1minoritypopulationinthe settingofMTCT. Methodology/PrincipalFindings:WedescribethecaseofafemalechildborntoanHIV-infectedmother,whichhadnot takenanyARVduringthepregnancy.Thechild’sfirstgenotypedemonstratedaminornon-nucleosidereversetranscriptase inhibitor (K101E), and during her treatment with reverse transcriptase and protease inhibitors full resistance to non- nucleosidereversetranscriptaseinhibitors(NNRTI)emerged(G190A).Phenotypic/genotypicanalysisofvariantquasispecies through yeast TyHRT assay was conducted to characterize minority resistant viral strains circulating in both mother and child.MaximumlikelihoodandBayesianMCMCphylogeneticanalyseswereperformedwithsamplesfromthepairtoassess geneticrelat