TheUKCollabora-veHIVCohort(CHIC)Study

CarolineSabinUCLMedicalSchool

Background

•  Informa0ononHIVinfec0onintheUKcomesfromavarietyofsources;theseareo=enlimitedinscope

•  Manyclinicalcentresrou0nelycollectinforma0onaboutpa0entswithHIVinfec0onwhentheyaCend:–  ProvidesanidealopportunitytostudyHIV‐infectedindividualsintheirclinicalseHng

–  Canuseexis0nginfrastructurefordatacollec0on–  Canincludepa0entsfromawidevarietyofclinicssothatthecohortbecomesmorerepresenta0veofindividualswithHIVinfec0onintheUK

UKCHIC:Objec0ves

TheUKCollabora0veHIVCohort(UKCHIC)wasini0atedin2001tocollaterou0nelycollecteddatafromHIV‐infectedindividualsaCendingsomeofthelargestclinicalcentresintheUKsince1stJanuary1996

Specificaimsare:•  Todescribethecharacteris0csofpa0entswithHIVundercare•  Toprovideinforma0ononexposuretocombina0on

an0retroviraltherapy(cART)andchangestotheimmunologicalandvirologicalstatusofpa0entsover0me

•  TomonitorthefrequencyofAIDSandsurvivalover0me

UKCHIC:Inclusioncriteria

  Aged>16years

  Seenatanyofthecentressince1/1/1996

  Electronicdataalreadyavailable

  Abletoprovidedataonanannualbasis

Pa#ents

Centres

UKCHIC:Par0cipa0ngclinics

ClinicalcentresBrightonandSussexUniversityHospitalsNHSTrustBartsandtheLondonNHSTrustChelsea&WestminsterNHSTrustMor0merMarketCentre,RF&UCMedicalSchoolHomertonUniversityHospitalNHSTrustKingsCollegeHospitalTheLothianUniversityHospitalsNHSTrustTheRoyalFreeNHSTrustNorthMiddlesexUniversityHospitalNHSTrustStMary’sNHSTrustNorthBristolNHSTrustLeicesterRoyalInfirmary

OthercentresResearchDept.ofInfec0onandPopula0onHealth,UCLMedicalResearchCouncilClinicalTrialsUnitHealthProtec0onAgency–CentreforInfec0ons(HPA‐CfI)

UKCHIC:Funding

•  StudyfundedbyMRCsince2001

•  Fundingprovides:–  Somedatabaseprogrammingsupport–  Projectco‐ordina0on–  Sta0s0calsupport–  Limitedfundingforclinicsforprovisionofdata

•  DatabasephysicallylocatedatMRCCTU–centrallylocatedand‘independent’ofallclinicalcentres

•  Projectco‐ordinatorandprincipalinves0gatorbasedatUCL(RoyalFreecampus)

UKCHIC:Processes

•  Centresprovidedataonallpa0entsseenattheircentresince1stJanuary1996

•  Datasentinpre‐agreedelectronicformatsothattheycanbeeasilymergedatco‐ordina0ngcentre

•  Includeshistoricdataoneachpa0entpriorto1996ifpa0entwasunderfollow‐upatthat0me

•  Datarequestedonallpa0entsseenatcentre,evenifnotseensince1/1/96(toimprovede‐duplica0onprocess)

UKCHIC:Datasets

Demographics (patient, centre, ethnicity, risk group, first and last

attendance)

Clinical events - AIDS, death

Antiretroviral therapy

Hepatitis (B/C) tests

Laboratory-defined toxicities

Adherence Prophylaxis (PCP)

CD4 / viral load data

Serious non-AIDS

events

Dates of in-patient and out-

patient attendances

Characteris0csofpa0entsinUKCHIC

Centre Numberofpa0entsBrighton 2,772Mor0merMarket/Archway 5,904St.Mary’s 5,188Kings 3,461ChelseaandWestminster 10,286BartsandtheLondon 3,717RoyalFree 4,150EdinburghWesternGeneral 1,012Homerton 1,247NorthMiddlesex 1,494Bristol 1,026Leicester 625Numberofpa0entsincludedindataset

‐Beforede‐duplica0on 40,882‐A=erde‐duplica0on 35,377

UKCHIC2009dataset

Characteris0csofpa0entsinUKCHIC

n %

Totalnumberofpa0ents 35377 100.0Sex: Female 8659 24.5

Riskgroup: Homo/bisexual 17984 50.8IDU 1396 4.0Heterosexual 11149 31.5Other/notknown 4848 13.7

Ethnicity: White 19912 56.3BlackAfrican 8543 24.2Other 4711 13.3Notknown 2211 6.3

Median(IQR)ageatfirstentryintocohort(years):

30 24‐36

UKCHIC2009dataset

Non‐uptakeofcART(KateCober,Mar0nFisher,MargaretJohnson)

KoberCetal.AbstractP5,SecondJointConferenceofBHIVAandBASHH,Manchester,2010

•  CurrentBHIVAguidelinesrecommendthatallpa0entswithaCD4count<350cells/mm3shouldbeofferedcART

•  PreviousanalysesofUKCHICdatasetsuggestedthatonly10‐15%ofpa0entswithaCD4countof200‐350cells/mm3ini0atedcARTinthenextsixmonths

•  Re‐visitedques0onbyiden0fyingallpa0entswithconfirmedCD4count<350cells/mm3whohadnotini0atedcARTby0meoflastclinicvisitin2007‐2009

Non‐uptakeofcART(KateCober,Mar0nFisher,MargaretJohnson)

•  534/5613(9.5%)ofpa0entswithconfirmedCD4count<350cells/mm3hadnotstartedcART

•  Frommul0variableanalyses,thosestar0ngHAARTwereolder,lesslikelytobeIDU,lesslikelytobeofblackAfricanethnicity,andhadtheirlowCD4countmeasuredinmorerecentyears,BUTtendedtohaveamorerapidlydecliningCD4count

•  Thus,whilstthereisasmallcohortofpa0entswhoremainuntreateddespitehavinghadalowCD4count,thesepa0entsprobablyhavecountsthatarehoveringaroundthe350cells/mm3mark

KoberCetal.AbstractP5,SecondJointConferenceofBHIVAandBASHH,Manchester,2010

Long‐termtrendsinCD4countoncART(RachaelHughes,JonathanSterne)

HughesRetal.ManuscriptsubmiCedforpublica0on

ModelledgeometricmeanCD4trajectoriesamongpa0entswitha)allHIVVL<1000copies/mlorb)atleastoneHIVVL

>1000copies/mlsix‐monthspost‐cARTa) b)

Long‐termtrendsinCD4countoncART(RachaelHughes,JonathanSterne)

HughesRetal.ManuscriptsubmiCedforpublica0on

•  ThegreatestimpactofvirologicalfailureonsubsequentCD4countsoccurredinthefirst44daysa=eraVL>1000copies/ml

•  VLs>10,000copies/mlhadagreaterimpactonfutureCD4trendsthanVLsof1000‐10,000copies/ml

•  AlthoughtheimpactonsubsequentCD4countsdecreasedas0mesincevirologicalfailureincreased,theeffectcon0nuestopersistbeyondoneyear

Timetrends(LoveleenBansi,AndrewPhillips)

Observedandprojected(withuncertaintybounds)propor0onofpa0entswithcurrentCD4<200cells/mm3andpropor0onofpa0entsonARTwith

viralload<50copies/mLwithuncertaintyboundsintheUK

BansiLetal.HIVMedicine2010(inpress)

2000 2002 2004 2006 2008 2010 2012 Year under follow up

Timetrends(LoveleenBansi,AndrewPhillips)

Observedandprojected(withuncertaintybounds)numberofpa0entswithETCFintheUKandthenumberofpa0entswithcurrentVL>50copies/mL

a=erETCF

BansiLetal.HIVMedicine2010(inpress)

2000 2002 2004 2006 2008 2010 2012 Year under follow up

UKCHIC:Howdoweprotectyourdata?

•  Adheretoextensiveconfiden0alitypolicy•  Coversen0reprocessfromini0alspecifica0onofdatasetstomanagementofdatasetspost‐publica0on

•  PolicydevelopedandmaintainedbyUKCHICDataProtec0onsub‐group,withinputfrom:–  LondonCaldicoCguardians–  StaffatMedicalResearchCouncilHeadOffice–  HealthProtec0onAgency–  Community(SimonCollins)–  Bri0shMedicalAssocia0on(BMA)

UKCHIC:Howdoweprotectyourdata?

•  Alldatapseudonymisedpriortosubmission;cannotiden0fyindividualsfromsubmiCeddatasets

•  DatafilesencryptedthentransferredtoMRCwebsiteusingsecureweb‐basedtransfer(=p)‐NODATAFILESTRANSFERREDVIAMEMORYSTICKS!

•  AlldatachecksperformedatMRCCTU;anycommunica0onwithlocaldatamanagersperformedusingsecuretransferand/orencryptedfiles

•  Allpaperrecordskeptinlockedfilesanddestroyedwhennolongerrequired

UKCHIC:Howdoweprotectyourdata?

•  De‐duplica0on/linkageperformedusingpre‐definedalgorithmwithoutneedforpersonalinforma0on

•  Dateofbirthrequiredforde‐duplica0on,butremovedfromfinaldatasetpriortodistribu0on

•  Datasetdistributedtothoseperforminganalysesa=erofficialapprovalofaprojectproposalbytheUKCHICSteeringCommiCee;onlytheminimumdatasetrequiredforeachanalysisisdistributed

•  Datasetsprovidedtoexternal‘collabora0ons’(e.g.COHERE,PLATOstudies)arefurtherblinded

Summary

•  Rou0nelycollectedclinicaldataoffersopportuni0esforconduc0ngclinicalresearchatafrac0onofthecostofequivalently‐sizedepidemiologicalstudies

•  Abletomonitoradherencetoguidelinesandiden0fyareaswhereclinicalmanagementcouldbeimproved

•  Studyfindingscitedinna0onal(BHIVA)andinterna0onal(EACS,USDHSS,IAS)treatmentguidelines,andfrequentlydiscussedincommunityliterature–thus,findingsfromstudyhavecontributeddirectlytoimprovementsinpa0entcare

ResearchDepartmentofInfec#onandPopula#onHealth,UCLMedicalSchool:CarolineSabin,TeresaHill,LoveleenBansi,AndrewPhillips,SusieHun0ngton

MedicalResearchCouncilClinicalTrialsUnit(MRCCTU):AbdelBabiker,DavidDunn,AdamGlabay,KholoudPorter

BrightonandSussexUniversityHospitalsNHSTrust:Mar0nFisher,DuncanChurchill,NickyPerry,AnthonyPullin

ChelseaandWestminsterNHSTrust:BrianGazzard,SteveBulbeck,JemimaClarke,SundhiyaMandalia

KingsCollegeLondonSchoolofMedicine,GKTHospitals:FrankPost,PhilippaEasterbrook,YasarKhan,ParagiPatel,Fa0mahKarim,StephenDuffell,FowziaIbrahim

Mor#merMarketCentre,UCLMedicalSchool:RichardGilson,Shuk‐LiMan,IanWilliams

RoyalFreeNHSTrust/UCLMedicalSchool:MargaretJohnson,ClintonChaloner,HelenGrabowska,FionaLampe,DewiIsmajaniPuradiredja,MikeYoule,ColeCeSmith

ImperialCollegeHealthcareNHSTrust:JohnWalsh,NickyMackie,AlanWinston,Chris0anKemble,JonathanWeber

BartsandtheLondonNHSTrust:ChloeOrkin,KevinJones,RachelThomas

HomertonUniversityHospitalNHSTrust:JaneAnderson,SajidMunshi

TheLothianUniversityHospitalNHSTrust:CliffordLeen,AlanWilson

NorthMiddlesexUniversityHospitalNHSTrust:AchimSchwenk,JonathanAinsworth

HealthProtec#onAgencyCentreforInfec#ons:ValerieDelpech

NorthBristolNHSTrust:MarkGompels,DebbieDooley

UKCHICisfundedbytheUKMedicalResearchCouncil

UKCHIC:Acknowledgements