Association of pol Diversity with Antiretroviral Treatment Outcomes among HIV-Infected African Children.docVIP

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Association of pol Diversity with Antiretroviral Treatment Outcomes among HIV-Infected African Children.doc

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Association of pol Diversity with Antiretroviral Treatment Outcomes among HIV-Infected African Children

AssociationofpolDiversitywithAntiretroviral TreatmentOutcomesamongHIV-InfectedAfrican Children IrisChen1*,LeilaKhaki1,JaneC.Lindsey2,CarrieFry3,MatthewM.Cousins1,RobertF.Siliciano4, AvyViolari5,PaulPalumbo6,SusanH.Eshleman1* 1Dept.ofPathology,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica,2CenterforBiostatisticsinAIDSResearch,Harvard SchoolofPublicHealth,Boston,Massachusetts,UnitedStatesofAmerica,3FrontierScienceandTechnologyResearchFoundation,Amherst,NewYork,UnitedStatesof America,4Dept.ofMedicine,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica,5PHRU,ChrisBaragwanathHospital,Soweto, SouthAfrica,6Depts.ofPediatricsandMedicine,GeiselSchoolofMedicineatDartmouth,Lebanon,NewHampshire,UnitedStatesofAmerica Abstract Background:InHIV-infectedchildren,viraldiversitytendstoincreasewithageintheabsenceofantiretroviraltreatment (ART).WemeasuredHIVdiversityinAfricanchildren(ages6–36months)enrolledinarandomizedclinicaltrialcomparing twoARTregimens(CohortIoftheP1060trial).Childreninthiscohortwereexposedtosingledosenevirapine(sdNVP)at birth. Methods:HIVdiversitywasmeasuredretrospectivelyusingahighresolutionmelting(HRM)diversityassay.Sampleswere obtainedfrom139childrenattheenrollmentvisitpriortoARTinitiation.SixregionsoftheHIVgenomewereanalyzed:two ingag,oneinpol,andthreeinenv.AsinglenumericHRMscorethatreflectsHIVdiversitywasgeneratedforeachregion; compositeHRMscoreswerealsocalculated(meanandmedianforallsixregions). Results:Inmultivariablemedianregressionmodelsusingbackwardsselectionthatstartedwithdemographicandclinical variables,olderagewasassociatedwithhigherHRMscores(higherHIVdiversity)inpol(P=0.005)andwithhighermean (P=0.014)andmedian(P,0.001)HRMscores.Inmultivariablemodelsadjustedforage,pre-treatmentHIVviralload,pre- treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P=0.016) and longer time to study endpoints (virologic failure