Factors Influencing the Emergence and Spread of HIV Drug Resistance Arising from Rollout of Antiretroviral Pre-Exposure Prophylaxis (PrEP) 英文参考文献.docVIP

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Factors Influencing the Emergence and Spread of HIV Drug Resistance Arising from Rollout of Antiretroviral Pre-Exposure Prophylaxis (PrEP) 英文参考文献.doc

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Factors Influencing the Emergence and Spread of HIV Drug Resistance Arising from Rollout of Antiretroviral Pre-Exposure Prophylaxis (PrEP) 英文参考文献

FactorsInfluencingtheEmergenceandSpreadofHIV DrugResistanceArisingfromRolloutofAntiretroviral Pre-ExposureProphylaxis(PrEP) UmeL.Abbas1*,GregoryHood2,ArthurW.Wetzel2,JohnW.Mellors3 1Department of Infectious Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America, 2Pittsburgh Supercomputing Center, Pittsburgh, Pennsylvania,UnitedStatesofAmerica,3DivisionofInfectiousDiseases,SchoolofMedicine,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica Abstract Background: The potential for emergence and spread of HIV drug resistance from rollout of antiretroviral (ARV) pre- exposure prophylaxis (PrEP) is an important public health concern. We investigated determinants of HIV drug resistance prevalenceafterPrEPimplementationthroughmathematicalmodeling. Methodology:Amodelincorporatingheterogeneityinage,gender,sexualactivity,HIVinfectionstatus,stageofdisease, PrEPcoverage/discontinuation,andHIVdrugsusceptibility,wasdesignedtosimulatetheimpactofPrEPonHIVprevention anddrugresistanceinasub-Saharanepidemic. Principal Findings: Analyses suggest that the prevalence of HIV drug resistance is influenced most by the extent and duration of inadvertent PrEP use in individuals already infected with HIV. Other key factors affecting drug resistance prevalenceincludethepersistencetimeoftransmittedresistanceandthedurationofinadvertentPrEPuseinindividuals whobecomeinfectedonPrEP.Fromuncertaintyanalysis,themedianoverallprevalenceofdrugresistanceat10yearswas predictedtobe9.2%(interquartilerange6.9%–12.2%).Anoptimisticscenarioof75%PrEPefficacy,60%coverageofthe susceptiblepopulation,and5%inadvertentPrEPusepredictsariseinHIVdrugresistanceprevalencetoonly2.5%after10 years.Bycontrast,inapessimisticscenarioof25%PrEPefficacy,15%populationcoverage,and25%inadvertentPrEPuse, resistanceprevalenceincreasedtoover40%. Conclusions: Inadvertent PrEP use in previously-infected individuals is the major determinant of HIV drug resistance prevalence arising from PrEP. Both t