Reappearance of Minority K103N HIV-1 Variants after Interruption of ART Initiated during Primary HIV-1 Infection 英文参考文献.docVIP

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Reappearance of Minority K103N HIV-1 Variants after Interruption of ART Initiated during Primary HIV-1 Infection 英文参考文献.doc

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Reappearance of Minority K103N HIV-1 Variants after Interruption of ART Initiated during Primary HIV-1 Infection 英文参考文献

ReappearanceofMinorityK103NHIV-1Variantsafter InterruptionofARTInitiatedduringPrimaryHIV-1 Infection KarinJ.Metzner*,ChristineLeemann,FrancescaDiGiallonardo,ChristinaGrube,AlexandraU.Scherrer, DominiqueBraun,HerbertKuster,RainerWeber,HuldrychF.Guenthard DivisionofInfectiousDiseasesandHospitalEpidemiology,UniversityHospitalZurich,UniversityofZurich,Zurich,Switzerland Abstract Background:IntheZurichPrimaryHIVinfectionstudy(ZPHI),minoritydrug-resistantHIV-1variantsweredetectedinsome acutely HIV-1-infected patients prior to initiation of early antiretroviral therapy (ART). Here, we investigated the reappearanceofminorityK103NandM184VHIV-1variantsinthesepatientswhointerruptedefficientearlyARTafter8–27 months according to the study protocol. These mutations are key mutations conferring drug resistance to reverse transcriptaseinhibitorsandtheybelongtothemostcommonlytransmitteddrugresistancemutations. Methodology/Principal Findings: Early ART was offered to acutely HIV-1-infected patients enrolled in the longitudinal prospectiveZPHIstudy.Sixpatientsharboringandelevenpatientsnotharboringdrug-resistantvirusesatlowfrequencies prior to ART were included in this substudy. Minority K103N and M184V HIV-1 variants were quantified in longitudinal plasma samples after treatment interruption by allele-specific real-time PCR. All 17 patients were infected with HIV-1 subtypeBbetween04/2003and09/2005andreceivedLPV/r+AZT+3TCduringprimaryHIV-1infection(PHI).MinorityK103N HIV-1variantsreappearedaftercessationofARTintwooffourpatientsharboringthisvariantduringPHIandevenpersisted inoneofthosepatientsatfrequenciessimilartothefrequencyobservedpriortoART(,1%).TheK103Nmutationdidnot appearduringtreatmentinterruptioninanyotherpatient.MinorityM184VHIV-1variantsweredetectedintwopatients afterARTinterruption,oneharboringandonenotharboringthesevariantspriortoART. Conclusion:MinorityK103NHIV-1variants,presentinacutelyHIV-1infectedpatientspriortoearlyART,canreappearand persistafterinterruptionofsuppre