UltraRapidDiagnosticTestingEarlyInfantHIVDiagnosis

PaoloMaggioreICREID

March12th,2018AddisAbaba

1. Public health case for point-of-care early infant HIV diagnosis

2. Implementation strategies

3. Financial case

Agenda

Thougheffortstoscale-upconventionalEIDtestinghaveincreasedaccess,longturnaroundtimes(TAT)ofresultavailabilityandreceiptbycaregiverunderminetheseefforts

17

17

26

26

7

7

6

32

32

19

19

14

14

4

6

2

9

0

7

0

2

0 20 40 60

Cam2016- Mar2017/Biker

Cam2016- Mar2017/SMS

Malawi2016/R4H

Malawi2016/SMS

Malawi2017/R4H

Malawi2017/SMSRaspPi

Kenya2017

SampleCollectiontoLabLabtoTestDateTesttoFacilityReceipt

0

11.5

20

23

26

7

28

14

23

5

0 10 20 30 40 50 60

Facility1

Facility2

Facility3

Facility4

Facility5

Facility6

Facility7

Facility8

Facility9

Facility10

TurnaroundTime(Days)

SampleCollectiontoReceivedinLabReceivedinLabtoTestDateTestDatetoDispatchDispatchtoFacilityReceiptFacilityReceipttoCaregiverReceipt

Alereqused atbaselineaccountsforTAT≤1day

Conventional testingwasavailableon-site

Referralsitessendingsampletoreferencelabforconventionaltesting

CountryXiNov2016toApr2017

2014 201820162013 2015 2017 2019

Assay Evaluator Sampletype

Sensitivity (95%CI) Specificity(95%CI)

ARDx qWHOPQCDC/NHLS WB 98.67% (95.27-99.84) 100.00% (97.59-100.00)

EIDConsortium WB 99.00%(96.45-99.88) 99.97%(99.83-100.00)

Xpert

WHOPQCDC/NHLS WB 98.86%(93.83-99.97) 100.00%(97.55-100.00)

EIDConsortium WB 96.79%(92.68-98.95) 99.91%(99.76-99.97)

WHOPQCDC/NHLS DBS 99.34% (96.40-100.00) 100.00%(97.60-100.00)

TwoPOCEIDdeviceshavebeenshowntohavehighdiagnosticaccuracyandhavebeenavailablesince2016

CepheidGeneXpert AbbottRapidDiagnosticsq

Inbothstudysettingsandroutineuseacrosscountries,POCEIDdramaticallyincreasesthenumberofinfantsonARTandreducesthetimetoinitiation

Country Setting Device/Sample

#ofsites n %resultreturntocaregiver

TATresultreturn

%ARTinitiation TATARTInitiation

≤30#days

Sameday

≤60days

Sameday

Mozambique(Maputo,Sofala)

cRCT AlereQ,WB

SOC - 8 1876 0.32% 0% 125 12.8%NA

127

POC- 8 2034 98.7% 98.2% 0 89.7% 0

Malawi Observa-tionalpre/post

AlereQ,WB

7pre 963 18.1% 0% 56 41.9% 43.8% 38

7post 789 100% 99.5% 0 91.1% 70.7% 0

#MozambiqueSOC:7.2%within60days;Malawipre:41%within60days.NA=notavailable

Nine-country(EGPAF)

M&E AlereQ,WB&Xpert,WB

SOC – 96 2,900 20.9% 0% 55 43.2% 0% 49

POC– 245 13,201 99.8% 69.8% 0 91.8% 66.7% 0

M&E– RoutineUse

StudyUse

1. Public health case

2. Implementation strategies

3. Financial case

Agenda

0123456789

10

117

534

952

369

787

110

4512

1913

9315

6717

4119

1520

8922

6324

3726

1127

8529

5931

3333

0734

8136

5538

2940

0341

7743

51

EIDTestsp

erDay.

IndividualFacilities

Country#2

0

2

4

6

8

10

12

14

16

18

20

1 65 129

193

257

321

385

449

513

577

641

705

769

833

897

961

1025

1089

1153

1217

1281

1345

1409

1473

1537

1601

EIDTestsp

erDay

IndividualFacilities

Country#4

-1

1

3

5

7

9

11

13

15

1 34 67 100

133

166

199

232

265

298

331

364

397

430

463

496

529

562

595

628

661

694

EIDTestsp

erDay

IndividualFacilities

Country#3

0

20

40

60

80

100

120

1 72 143

214

285

356

427

498

569

640

711

782

853

924

995

1066

1137

1208

1279

1350

1421

1492

1563

1634

EIDTestsp

erDay

IndividualFacilities

Country#1

Amajority(>50%)ofHEIsareconcentratedinarelativelysmallproportionofsites(between67- 188sitespercountry),allowingahigh-yieldplacementstrategy

80%ofpatientsat26%ofsites10%ofsitesaccountfor59%ofpatients

5%ofsites=47%ofpatients1%ofsites=24%ofpatients

80%ofpatientsat36%ofsites10%ofsitesaccountfor47%ofpatients

(5%ofsites=33%ofpatients1%ofsites=13%ofpatients)

80%ofpatientsat42%ofsites10%ofsitesaccountfor39%ofpatients

(5%ofsites=26%ofpatients1%ofsites=9%ofpatients)

80%ofpatientsat19%ofsites10%ofsitesaccountfor69%ofpatients

(5%ofsites=55%ofpatients1%ofsites=25%ofpatients)

AcombinationofimplementationstrategiescanbeusedtoincreaseaccesstoPOCtestingwhileoptimizingdeviceutilizationrates

8

Stand-AloneSitesReceivesamplesdirectlyfromclientsand

performPOCEIDtestsonsite

Hub-and-SpokeNetworksHubsitesprovidetestingforpatientsatthatsiteandforspokesites.

Nearbyspokesitessendsamplestothehubsitesfortesting

Multiple-Entry-PointSitesReceivesamplesfromdifferentunitsorwardswithin

thesamehealthfacility

POCEID

Hub

Spoke Spoke

POCEID

IntegratedTestingSitesProcessdifferenttypesofPOCtests

(e.g.EID,TB,other)

Nutritionunit

POCEID

Pediatricward

MCHclinic

EID POC TB

Other

Hub-and-spoke:CourtesyEGPAF

WhileinfantsenrolledinPMTCTreceiveanHIVtestresultby2-monthsofage,thosenotenrolledintreatmentprogramsaremorelikelytobeinfectedandunlikelyeverbetested

AstudyinUgandacomparedroutineEIDtestingatalternativeentrypoint:68%ofHIV+ofinfantswerefoundoutsidethePMTCTprogram

0 4 8 12 16

EMTCT

Immunization

Outreach

Outpatient

Inpatient

Nutrition

HIV positivity rate (%)

p=0.000p=0.756p=0.041

p=0.001

p=0.002

• 3,600infantstested:117HIV+• Previousfacilityattendance:~50%ofinfantsin

last12mo.

• Medianageall:7months• MedianageHIV+:11months

Key Findings:• Nutrition and inpatient testing

combined identified the majority (68%) of infants.

Source:Kiyaga Cetal.“Wherehaveallthechildrengone?HighHIVprevalenceininfantsattendingnutritionandinpatiententrypoints.JIAS 2018,21:e25089

1. Public health case

2. Implementation strategies

3. Financial case

Agenda

Theall-incostpertestisimportantforcomparingthecostofdifferentplatforms,butonlytellspartofthestory

At80%utilizationthereagentsmakeupthemajorityofthecostpertestforalldevices• Thedevicecostper

testisminimal,exceptforthemoreexpensivePOCdevicesfromAlereandDRW

• SpecimentransportationmakesupasignificantcostforconventionalEIDtestingdevices

• WastemanagementforCepheidaddscost

$0$5

$10$15$20$25$30$35$40

Ceph

eid-

Omni

DRW-

SAMBA

II

Alere-

Q

Ceph

eid-C

onventional

Ceph

eid-N

ear-PO

C

Ceph

eid-

POC

Roche-

CAP/CT

M

Abbo

tt-

m20

00

Hologic-

Panthe

r

EID- AllinCostpertest-80%Utilization

Reagents(cartridges)- 80% Controls

Non-propriataryconsumables Device

Bundledincrementserviceandmaintenance Logistics

Distributormargins Sampletransportation

Specimencollectioncommodities Healthworkersalarytocollectspecimen

Healthworkersalarytoruntest WasteManagement

DistributorMargin DDP

ConventionalPoint-of-Care

Prod

uctA

Prod

uctB

Prod

uctC

Prod

uctA

Prod

uctB

Prod

uctC

Prod

uctA

Prod

uctB

Prod

uctC

NearPoint-of-Care

SystemdifferencesinthewayconventionalandPOCareimplementedandtheresultingresultreturnedrateshavealargeimpactonthecostperresultreturnedtothepatient

Aweightedaverageofresultsreturnedtothecaregiverorpatientfromeightstudiesis50%• Lostresultsincura

largefinancialcosttorepeattests

• WhenconsideringtheresultreturnedratesPOCEIDtestingbecomesmuchmorecomparablewithconventionalpricing

• TheCepheidGeneXpert couldbeappliedinseveralmodels

$0$10$20$30$40$50$60$70$80

Ceph

eid-

Omni

DRW-

SAMBA

II

Alere-

Q

Ceph

eid-

Conven

tional

Ceph

eid-N

ear-PO

C

Ceph

eid-

POC

Roche-

CAP/CT

M

Abbo

tt-

m20

00

Hologic-

Panthe

r

EID- AllinCostperresultreceived-80%Utilization

Reagents(cartridges)- 80% Controls

Non-propriataryconsumables Device

Bundledincrementserviceandmaintenance Logistics

Distributormargins Sampletransportation

Specimencollectioncommodities Healthworkersalarytocollectspecimen

Healthworkersalarytoruntest WasteManagement

DistributorMargin DDP

CostfromErrors- 80% CostfromLostResults- 80%

ConventionalNearPoint-of-CarePoint-of-Care

Prod

uctA

Prod

uctB

Prod

uctC

Prod

uctA

Prod

uctB

Prod

uctC

Prod

uctA

Prod

uctB

Prod

uctC

AnalysisofacountrypilotresultsindicatethatPOCEIDwaslessexpensivethanconventionaltestingperHIV+infantidentifiedandplacedontreatment2

CostperinfantinitiatedonART• Examiningthecostperinfantinitiatedontreatmentfromthei studyrevealsthatPOC

EIDwaslessexpensivethanconventionalEIDtesting.• ThiseffectwaslargelytheresultoflowerinitiationratesintheSOCarm,compared

withthePOCarmofthestudy,howeverHIVpositivityrateswerealsohigherinthePOCarmofthestudy

POCEIDtestingnearlyeliminates‘missing’resultsandincreasestheproportionofinfantsinitiated,butrequiresequipmentateachsite

Asite-by-siteanalysisofover10kPMTCTsitesineightcountrieswasconductedtodeterminethecostperHIV+infantinitiatedonARTateachsiteusingPOCEID.ThecostperHIV+infantinitiatedusingPOCranged from$551atthehighest-volumesiteto$35,882atthelowest-volumesite.

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