Effects of Genital Ulcer Disease and Herpes Simplex Virus Type 2 on the Efficacy of Male Circumcision for HIV Prevention Analyses from the Rakai Trials 英文参考文献.docVIP

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Effects of Genital Ulcer Disease and Herpes Simplex Virus Type 2 on the Efficacy of Male Circumcision for HIV Prevention Analyses from the Rakai Trials 英文参考文献.doc

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Effects of Genital Ulcer Disease and Herpes Simplex Virus Type 2 on the Efficacy of Male Circumcision for HIV Prevention Analyses from the Rakai Trials 英文参考文献

EffectsofGenitalUlcerDiseaseandHerpesSimplexVirus Type2ontheEfficacyofMaleCircumcisionforHIV Prevention:AnalysesfromtheRakaiTrials RonaldH.Gray1*,DavidSerwadda2,3,AaronA.R.Tobian4,MichaelZ.Chen1,FrederickMakumbi2,3 ,Tara Suntoke1,GodfreyKigozi3,FredNalugoda3,BoazIga3,ThomasC.Quinn5,6,LawrenceH.Moulton1, OliverLaeyendecker5,6,StevenJ.Reynolds5,6,XiangrongKong1,MariaJ.Wawer1 1BloombergSchoolofPublicHealth,JohnsHopkinsUniversity,Baltimore,Maryland,UnitedStatesofAmerica,2SchoolofPublicHealth,MakerereUniversity,Kampala, Uganda,3RakaiHealthSciencesProgram,Entebbe,Uganda,4DepartmentofPathology,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStates ofAmerica,5DepartmentofMedicine,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica,6DivisionofIntramuralResearch, NationalInstituteofAllergyandInfectiousDiseases,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica Abstract Background:Randomizedtrialsshowthatmalecircumcision(MC)reducestheincidenceofHIVandherpessimplexvirus type 2 (HSV-2) infections, and symptomatic genital ulcer disease (GUD). We assessed the role of GUD and HSV-2 in the protectionagainstHIVaffordedbyMC. MethodsandFindings:HIV-uninfectedmenwererandomizedtoimmediate(n=2,756)ordelayedMC(n=2,775)intwo randomizedtrialsinRakai,Uganda.GUDsymptoms,HSV-2status,andHIVacquisitionweredeterminedatenrollmentandat 6,12,and24mooffollowup.UlceretiologywasassessedbyPCR.Weestimatedtheprevalenceandprevalenceriskratios (PRRs)ofGUDincircumcisedversusuncircumcisedmenandassessedtheeffectsofHSV-2serostatusasarisk-modifying factor forGUD.We estimatedtheproportion oftheeffect ofMConHIV acquisitionthatwas mediatedby symptomatic GUD,andbyHSV-2infection.CircumcisionsignificantlyreducedsymptomaticGUDinHSV-2-seronegativemen(PRR=0.51, 95%[confidenceinterval]CI0.43–0.74),HSV-2-seropositivemen(PRR=0.66,95%CI0.51–0.69),andinHSV-2seroconverters (PRR=0.48,95%CI0.30–0.79).TheproportionofacuteulcersduetoHSV-2detectedbyPCRwas48.0%incircum