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Evaluation of point of care CD4 Testing in Ethiopia

Belete Tegbaru

National HIV Laboratory

The Ethiopian Health and Nutrition Research Institute

Addis Ababa, Ethiopia

6th IAS Conference

July 17-20, Rome Italy

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Presentation outline

• Background• Problems & questions• Objective• Plan of the evaluation• Methodology• Results• Summary• Expected Benefits of POC instruments• Anticipated Challenges for implementation

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233,361

Sites giving ART

Currently on ART

As of end of March 2011

HIV testing sites 2,309

Total Tested (2010/11) 6,592,896[+ve, 80,318 (1.2%)]

Sites giving CD4 testing service

6981. 108 Hospitals 2. 590 HCs

138All Hospitals

In Ethiopia (80 Million Population):

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Absence of on time CD4 count results (centralized and

referred)

Service

Lost follow-up

Cold chain system

Cost

Problems & questions

Distance to sites - TAT for results, HIV-DR?

transport ,storage & power interruption

Expertise, maintenance, training, referral linkage

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Objective

To evaluate a point-of-care technology (PIMATM) at different level for CD4

testing sites

• PimaTM CD4 + T cell Technology - against standard CD4 instruments

• To see the feasibility: of PIMA for CD4 testing• To see how far PimaTM CD4 + T cell Technology could help the

facilities to reach their patients on time

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Pima™ from Inverness Medical is a revolutionary point of care analyser. The Pima analyser employs the same static image analysis and counting principles as existing CD4 enumeration technology, in a compact, portable and robust package. Designed equally to suit the needs of the healthcare professional in the field or in the laboratory the Pima analyser is an affordable, effective and valuable tool in the management of HIV patients.1. CD4 count in 20 minutes 2. Battery powered 3. Portable & Robust 4. ‘Walk Away’ testing 5. Embedded software 6. No external calibration 7. On-board data archive

The Pima CD4 cartridge is a unique and breakthrough technology in the enumeration of T-helper cells in whole blood samples. Requiring only 5μL of capillary whole blood and with all test reagents sealed within the disposable cartridge, obtaining a CD4 count is now easier than ever.1. Insertion of the Pima CD4 cartridge into the Pima analyzer

automatically begins the testing process providing you with a direct CD4 measurement in 20 minutes.

2. Capillary whole blood – 5μL 3. No manual sample handling or processing 4. All reagents sealed in disposable cartridge 5. All dried reagents – No refrigeration needed

Handy & can be charged for those without

electricity

Reagent at room temperature

Can be done from

finger prick

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Plan of the evaluation

With standard Machines at central & Hospital lab (N=2 sites, 300 samples)

At Health center level; referred samples (n=7 sites, 750 samples) + Finger prick samples (300 samples)

Finger Prick samples(n=10 sites, 500 samples)

Phase-III

Phase-II

Phase-I

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Methodology

• Evaluate against standard machines (FACSCalibur and FACSCount)

• Intra-test, inter-test, inter-instrument, interpersonal variations were determined

• Referred samples for FACSCount to referral sites and PIMA on site results were compared

• Operational parameters (failure rate, rate of additional devices for planning and training were evaluated)

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ResultsFACSCalibur FACSCount PIMA

Total Samples 316 316 316

Total tested 303 297 306

Mean CD4 (cells/l)

314.9[290.6-339.3]

323.3[298.8-347.8]

317.3[293.2-341.3]

Range 9-997 4-1039 3-970

Failure rateNo result obtained

5(1.7%) 11 (3.7%) 8 (2.6%)

Total cartidges Damaged Retesting

PIMA-Lab 333 12 (3.6%) 15 (4.9%)

PIMA –HCs 140 2(1.4%) 15(10.7%)

Lab: 27(8.1%, 5.4-11.1)Site level: 17(10.7%,7.2-18.7] for planning

9.4% extra devices

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PIMA versus

Average (FACSCalibur and PIMA), cells/l

0 200 400 600 800

Diffe

ren

ce (

PIM

A-F

AC

SC

alib

ur)

, ce

lls/

l

-300

-200

-100

0

100

200

300

Mean +2SD

Mean

Mean - 2SD

Average (FACSCount and PIMA), cells/l

0 200 400 600 800

Diff

ere

nce

(P

IMA

-FA

CS

Co

un

t),

cells

/ l

-300

-200

-100

0

100

200

300

Mean+2SD

Mean

Mean-2SD

FACSCalibur FACSCount

PIMA

Bias (Mean) 2.3 cells/l -6.0cells/l

LOA (cells/l) [-106.1 to +110.7] [-102.4 to + 90.4]

Similarity (%) 103.2%, CV=15.5% 100.9%, CV=14.4%

Correlations R=0.960, p<0.001 R= 0.990, p<0.001

FACSCalibur FACSCount

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Number of patients

0 50 100 150 200 250 300

CD

4 T

ce

lls (

Ce

lls

/ l

)

0

200

400

600

800

1000

1200FACSCaliburPIMAFACSCount

Closeness of values

PIMA

0 500 1000 1500 2000 2500

FA

CS

Co

un

t

0

500

1000

1500

2000

2500

3000

CD4 Count (FACSCalibur, cells/l)

0 200 400 600 800 1000 1200 1400

CD

4 C

ou

nt

(PIM

A,

Ce

lls/

l)

0

200

400

600

800

1000

1200

1400

r= 0.960, p<0.001

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Parameters At our Lab evaluation(n=306)

Site in AA(n=141)

Within townPIMA Mean 317.3 331191FACSCount mean 323.3 349206Diff -6.0 -18

Similarity (%) 100.9 9810.6

Time to referral center and distance

5-10 min 10-15 Km, 20-30 Min

Period of referral NA 1x/week

TAT of results NA 3-4 days

PIMA versus FACSCount at health centers before and after referral

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FACSCalibur FACSCount

Phase-I(Lab based)

Total 9.2% 8.4%Downward 5.7% 6.1%Up-ward 17.3% 14.1%

Phase-II (Clinic based, N=140, Addis Ababa)

Total 1.4%Downward 0.93%Up-ward 3.1%

PIMA Misclassification rate

Taking 200 cells/µl as a cutoff

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Variability studies

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Sample

Vial-A Vial-B

TECH-A TECH-B

PIMA-1 PIMA-2 PIMA-1

TECH-A

PIMA-1

TECH-A TECH-A

Day-1

Day-2

<200: 103 cells/µl>200: 510 cells/µl

Each test= 10x

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Sample

Vial-A Vial-B

TECH-A TECH-B

PIMA-1 PIMA-2 PIMA-1

TECH-A

PIMA-1

Inter machine variation

Day-1

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Sample

Vial-A Vial-B

TECH-A TECH-B

PIMA-1 PIMA-2 PIMA-1

TECH-A

PIMA-1

Inter technician variation

Day-1

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Sample

Vial-A Vial-B

TECH-A TECH-B

PIMA-1

TECH-A

PIMA-1

Inter-assay variation

Day-1

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Sample

Vial-A Vial-B

TECH-A TECH-B

PIMA-1

TECH-A

PIMA-1

Intra-assay variation

Day-1

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Sample

Vial-A Vial-B

TECH-A TECH-B

PIMA-1 PIMA-2 PIMA-1

TECH-A

PIMA-1

PIMA-1 PIMA-1Day-2: Daily variation

Day-1

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Parameters CD4 (cells/µl)<200= 103 cells/µl>200= 510 cells/µl

WHO (CV%)

PIMASample

(n=10 times)

Inter-Machine ≤200 <15% 9.2%

>200 <10% 5.2%

Intra assay ≤200 <15% 13.1%

>200 <10% 6.4%

Inter assay ≤200 <15% 10.7%

>200 <10% 3.2%

Inter personnel ≤200 10.7%

>200 2.1%

Daily variation (after 16-17 hrs test)

<200 (109.6 cells), P= 0.10

10.7%

>200 (542.1 cells), p=0.52

2.1%

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Meaning of Pont-of-care

• In phase-II: 4 HCs tested 255 patients by both PIMA and FACSCount

Results obtained by FACSCount after referral

Total tested Results returned

Lost or no result & need re-draw blood

FACSCount 255 233 12 (4.7%)**

PIMA 255 253 2(0.7%)*

**- drawing of blood for 2nd time due to lost results* Reading failure

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Expected Benefits of POC instruments

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Patient

Program

Laboratory

• Expansion of sites• Reduce the cost of referral• Reduce the cost of cold chain• Serve the patient on site• Reduce lost follow-up

• Limited training required• Storage (room temp. and space)• Sample collection (easy and safe)• Can be done at lower level

• Get service on site• Initiate ART on time• No cost for transport & others• Follow their status at any time• Increase quality of life

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Anticipated Challenges for implementation

• Supply of reagents and machines Vs expansion– Mechanism to solve – connectivity and planning

• Maintenance Vs expansion– Preventive maintenance free-– Technical service replacement strategy

• CD4% for pediatric cases– development

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Summary1. Good agreement with standard machines with low bias

and good percentage of similarity

2. On Planning: a total of 9.4% extra devices required at lab & site level

3. Failure rate on testing= 8/306= 2.6% at lab level

4. Gives extra advantage – No need to re-draw blood -point-of-care ~5% of the cases

5. Power interruption was not a problem at site level

6. The intra-, inter-tests are within WHO recommendations for ≤200 and >200 cells/l CD4 Tests

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Collaborating Individuals

Dr. Tsehaynesh Mesele EHNRIDr. Almaz Abebe EHNRIMr. Dereje Teshome

EHNRIMr. Ermias Hailu EHNRIMr. Feyissa Challa EHNRIMr Habteyes Hailu EHNRIMrs. Yodit Alemayehu EHNRIKatherine Theiss-Nyland

CHAIDr. Peter Trevor

CHAI

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Ethiopian Health and Nutrition Research Institute –Organize and lead the evaluation

CHAI: Financial, material and technical support

Alere: Training of laboratory personnel at the National HIV laboratory

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