simplification, cost-reduction strategies and examples from the field

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Simplification, cost-reduction strategies and examples from the field . Teri Roberts Diagnostics Advisor MSF Access Campaign. Virological Monitoring Detects Treatment Failure Early On. Adapted from Bartlett et al. Lancet Infect Dis 2009. - PowerPoint PPT Presentation

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Simplification, cost-reduction strategies and examples from the field Teri RobertsDiagnostics AdvisorMSF Access Campaign

1Virological Monitoring Detects Treatment Failure Early On

Adapted from Bartlett et al. Lancet Infect Dis 20092

Across programmes: 2% of treated patients are on 2nd-line ARTIn South Africa (Khayelitsha), where routine virological monitoring is available: 12% on 2nd-line after 5 years3HIV Policy and Progress Indicators Across 16 CountriesCameroonCARDRCEthiopiaGuineaIndiaVL for Tx failureOPTOPTOPTNOOPTREQRoutine VLOPTNONONONONOAvailableLTDLTDLTDLTDLTDLTDKenyaLesothoMalawiMozambiqueMyanmarVL for Tx failureOPTOPTREQOPTOPTRoutine VLNONONOREQNOAvailableYESLTDLTDNOLTDSouth AfricaSwazilandUgandaZambiaZimbabweVL for Tx failureREQOPTOPTOPTOPTRoutine VLREQNOOPTOPTNOAvailableYESLTDLTDLTDLTDLynch et al. Science 2012OPT: optional; REQ: required; LTD: limited4How to increase access to virological monitoring?Reduce complexityReduce priceMarket entryVolumeCompetitionOpen and polyvalent platformsPrice transparencyField validate new and current tests (point of care and lab-based)Perform operational research to define best adapted and most feasible tests for different settingsIntroduce viral load testing in a phased in approachDefine testing frequencyReplace CD4 monitoring with viral load monitoringImplement evidence-based algorithms to prioritise patients

Reduce priceIncreased demand and supply, economies of scale, competition and the use of quality-approved open and polyvalent systemsIncreased price transparency

Introduce viral load testing in a phased in approachInvestigate the possibility of reducing testing frequency in long-term stable patientsInvestigate the possibility of gradually replacing CD4 monitoring with virological monitoring completelyImplement evidence-based algorithms to prioritise patients most urgently in need of virological monitoring

5Laboratory-based testPoint-of-care testSamplePlasma, DBSFingerstick, heelstickSample volume200 1000l100lSample prepSimple, no contaminationSimple, part of POC testConsumablesMinimal, open accessMinimal (1 lancet, 1 collection tube, 1 cartridge)ReagentsNo cold storage, stable 40C for 18 monthsPart of cartridge, no cold storage, stable 40C for 18 monthsPowerAC and batteryAC, battery (8 hours), solarInstrumentOpen access and polyvalent, 1 room, no contaminationClosed system, automated, small and lightweight, environmentally robust (heat, humidity, rigorous movement)Hands-on time1 hour10 minutesTime to result1 day30 minutesRangeQuantitative, all subtypes, 50 copies/mlQuantitative / semi-quantitative, all subtypes, 1000 copies/mlTraining / skillMediumMinimal, basic (2 days), no precision pipettingRegulationWHO PQ (opt CE, FDA)WHO PQ (opt CE, FDA)Cost per test$10$8Instrument$5000 (all required)$1000 (single instrument)6Simplifying sample transport by using DBSQuick processing of whole bloodInefficient sample networksAlternative: dried blood spotsLong distances, ambient temperatureTime to result: e-health, m-healthFingerprick DBSNucliSENS EasyQ HIV-1 v2.0 viral load test (bioMerieux) for DBSMSF validation of fingerprick DBS in MalawiOther tests for use with DBS?

Whole blood requires processing within 6 hours of blood draw.Sample networks, especially in remote areas, are not able to get blood to the lab within a short time frame.The alternative is to use dried blood spots (DBS).DBS can be easily preserved in an airtight bag and transported over long distances at ambient temperature (even posted).Result turn around times can be expedited using electronic and mobile health technologies.A venous blood draw must be performed by a qualified person e.g. nurse or lab technician so the alternative is to use fingerprick blood.MSF currently use the NucliSENS EasyQ HIV-1 v2.0 viral load test (bioMerieux) in Malawi because it is the only test that has received regulatory approval for use with DBS (prepared from venous blood).MSF have also validated the preparation of DBS from fingerprick blood in Malawi to enable task shifting to lay-workers (the study found that fingerprick DBS was a viable alternative to plasma for measuring viral load). We encourage manufacturers of other lab-based viral load tests to validate their platforms on DBS and apply for regulatory approval.

7NucliSENS EasyQ HIV-1 v2.0 (bioMrieux)Thyolo district hospital, MalawiDBS validatedReal time NASBA (isothermal signal amplification), RNA specificLogistical challenges:laboratory infrastructure unreliable power supplyunreliable water supply provision of RNAse-free waterunreliable air-conditioningnon-adherence to cold chain transportation, especially at customsinability to find local laboratory technicians with molecular biology expertiselack of in-country trouble-shooting and maintenance services

1. Extraction room

2. Amplification roomMSF have successfully implemented this test at district level in Thyolo, MalawiOne of the main reasons for choosing this test was that it was the only lab-based test validated for use with DBS (regulatory approval by WHO PQ and CE-IVD)Technology is real time NASBA (isothermal signal amplification), RNA specificLogistical challenges:laboratory infrastructure unreliable power supplyunreliable water supply provision of RNAse-free waterunreliable air-conditioningnon-adherence to cold chain transportation, especially at customsinability to find local laboratory technicians with molecular biology expertiselack of in-country trouble-shooting and maintenance services.

8Generic HIV viral load assay (Biocentric)Nhlangano health center, SwazilandOpen system, low costReal time RT-PCR (DNA and RNA)Logistical challengesUse of plasma as a sample type (use of DBS is research use only)Most of the other challenges as for the NucliSENS test

9ExaVirTM Load Version 3 (Cavidi)Yangon, Myanmar (field site is in Shan state)Subtype independent, relatively low cost, minimal lab requirements, not as prone to contamination and not as dependent on precision pipetting as molecular lab testsELISA of HIV reverse transcriptase activity

Challenges include:Must be performed on plasmaPlasma must be frozen at -20CNeed for back-up vacuum pumpRelatively low through-put for lab testGood water quality is essentialPositive and negative controls must be supplied in-houseSample preparation to isolate the reverse transcriptase enzyme is labour-intensive

10Formore information, please grab a copy of our viral load report (also available on our website: www.msfaccess.org)

1112Performance evaluation of SAMBA semi-quantitative HIV viral load test for therapy monitoring in resource-poor settings

Dr. Suna BalkanMSF Aids Working Group 1313Inclusions/monthCumulated patients under ART 0100020003000400050006000700020012002200320042005Scaling-up in the MSF project Chiradzulu district, Malawi

Decentralisation

Task shifting Need for a POC VL14SAMBA system characteristicsAll HIV1 subtypes & recombinantsThreshold 1,000 copies/mlHeat stability at 50C

Robust & simple instrument

No or minimum electricityMinimum handlingNo risk of contaminationTurn around time allowing same day resultAffordable cost Can detect Groups M, N, O & recombinantsCut-off at 1,000 copies/mlHeat stable reagents; no cold chain transport or storageIsothermal amplification with simple visual detection Low power requirement 350WPreloaded reagents in a closed cartridgeTest time = 90 minutes with throughput of 24/day at 6.5 hr working day

MSF requirements SAMBA

1515Visual readout of SAMBA semi-quant VL test3.3 log)TotalSAMBA >1,000223438SAMBA < 1,000932196Total (%)95 (71%)4 (3%)35 (26%)134Roche Taqman v2 (copies/ml)1818Malawi13.2 million population mainly rural 1 million HIV-infectedMSF project based in a rural district1 hospital (laboratory),10 health centresHIV care in 2000,decentralisation in 200325 000 patients followed under ART 80% followed in the 10 decentralised health centresIntegrated project with MOH

MSF Chiradzulu project background

19MSF Arua project background

Northwestern UgandaArua + catchment population : 1,5 MHIV prevalence 3%ART project since 2002Arua District Hospital7000 patients followed under ART Integrated project with the MOH

20SAMBA tested on-site by MSF technician

Roche TaqMan v2 at Royal London Hospital Abbott RealTime PCR at AddenbrookeSAMBA field trials in Malawi and Uganda200 HIV+ patients in Malawi 154 HIV+ patients in Uganda recruited from HIV clinic during routine visit200 l fresh plasma Frozen plasma shipped directly Results to MSF Discordant SAMBA/Roche

All testing blinded to each other2121Malawi results SAMBA vs Roche TaqMan v2

Viral Load (cp/ml)< 500(2,000 (>3.3 log)TotalSAMBA >1,000444654SAMBA < 1,00014240146Total (%)146 (73%)8 (4%)46 (23%)200Overall concordance with Roche v2 = 98% (196/200)Roche TaqMan version 2* Roche TaqMan accuracy is +/- 0.3 Log per package insert 2222Uganda results SAMBA vs Roche TaqMan v2

Viral Load (cp/ml)< 500(2,000 >(3.3 Log)TotalSAMBA >1,00020*5658SAMBA < 1,000902*496Total (%)92 (60%)2 (1%)60 (39%)154Overall concordance with Roche v2 = 96.1% (148/154)Roche TaqMan v2* Roche TaqMan is 0.3 Log accuracy (package insert) 2323ConclusionSAMBA platform is much simpler than currently available molecular technologies which require highly-trained personnel and sophisticated infrastructure only available in centralised laboratoriesSAMBA device is much easier to handle and being a closed system, prevents contamination by ampliconsStaff training requirement for SAMBA is minimal SAMBA can be implemented in lower healthcare levels such as district hospitals or health centres with a basic laboratory but supplied with electricityRoutine use of Samba will be now implemented in Arua and Chiradzulu with on going ev