the characterizing and understanding the hiv reservoir for
TRANSCRIPT
TheCharacterizingandUnderstandingtheHIVReservoirforEradication (CURE)cohort:anewresourceforunderstandingHIVpersistence
NatalieN.Kinloch1,2*,AniqaShahid1,2*,BruceGanase1,Hanwei Sudderuddin1,DelphineDuhirwe1,AlineTrevisan1,Zhong Dang1,F.HarrisonOmondi1,2,Hesham Ali3,ChadDickie4,SilviaGuillemi1,MarkHull1,MelKrajden5,ChansonJ.Brumme1,6,Marianne
Harris1,6,MarkA.Brockman1,2,Zabrina L.Brumme1,2(*showsco-firstauthors)
1BritishColumbiaCentreforExcellenceinHIV/AIDS,Vancouver,BritishColumbia;2FacultyofHealthSciences,SimonFraserUniversity,Burnaby,BritishColumbia;3PositiveLivingSocietyofBritishColumbia,Vancouver,BritishColumbia;4AVIHealthandCommunityServices,Victoria,BritishColumbia;5BritishColumbiaCentreforDisease
Control,Vancouver,BritishColumbia;6DepartmentofMedicine,UniversityofBritishColumbia,Vancouver,BritishColumbia
Poster ID BSP6.04
Presentingauthordeclaration:Ihavenoconflictsofinteresttodeclare
Contactusat:[email protected],[email protected]
1UNIVERSITYOFBRITISHCOLUMBIA
• ThedevelopmentofeffectiveHIVremissionorcurestrategieswillrequireadeeperunderstandingofinter-individualvariationinHIVreservoirsizeandcomposition.
• Tothisend,wehaveestablishedtheCharacterizingandUnderstandingtheHIVReservoirforEradication (CURE)cohortcomprisingindividualslivingwithHIVonlong-termcART.
Inthisposter,wedescribeCUREandexploreassociationsbetweenclinicalhistoryandlatentHIVreservoirsize.
2
BACKGROUND
3
METHODSParticipantrecruitmentand
informedconsentPBMCisolationBlooddraw(450mL) CD4isolationfromPBMCs
GenomicDNAextraction
QuantificationoftotalandintactlatentreservoirusingIntactProviral DNAassayviadropletdigitalPCR(ddPCR)forN=14 CUREparticipants
Ψflu
orescence
KinlochNetal,unpublished
4
RESULTS
Table1:CharacteristicsoftheCUREcohortParticipantsrecruitedsofar 31
Biological sex
Male 29
Female 2
Medianage(IQR) 57(48-63)years
HIVsubtype B
Median(IQR)estimateddurationofuncontrolledHIVinfection 7(2-15)years
Subsequentmedian(IQR) cART duration 13(9-20)years
Median(IQR)nadirCD4+ T-cellcount 280(120-630)cells/mm3
Median(IQR)archivedpre-cART plasmaavailable 5(2-16)samples/participant
• CUREisanewCanadianHIVcohort,comprisingindividualswithdiverseclinicalhistories,includingthosetreatedinearlyinfectionandlong-termHIVsurvivors,willadvanceourunderstandingofHIVpersistence.
• TheavailabilityofarchivedplasmaspecimenswillallowustoinvestigatethereservoirdiversityinthecontextofHIV'swithin-hostevolutionaryhistory. 5
0 1000 2000 3000 4000 50000
100
200
300
400Spearman's rho = 0.77p-value=0.001
Total HIV reservoir size
Gene
ticall
y in
tact
HIV
rese
rvoi
r size
Figure1:LatentHIVreservoirsizeoftheCUREparticipants
RESULTSFigure2:Positivecorrelationbetweentotalandintactreservoir
CONCLUSION
Nosignificantcorrelationsobservedbetweenuncontrolledinfectionduration,cART duration,nadirCD4count,andreservoirsize.
Total reservoir Defective reservoir Genetically intact reservoir0
200
400
6001000
2000
3000
4000
5000
HIV
Co
pie
s/m
illio
n C
D4+
T-c
ells
(N=14)