Pediatric Monitoring - CD4 issues inHIV Disease

Transfer of HIV Monitoring Technologies into Resource-Poor Settings: Moving the Field Forward

HIV Forum for Collaborative ResearchCROI Satellite Meeting

Boston, MA, February 26, 2005

Thomas N. DennyNew Jersey Medical School

Newark, NJ, USAdennytn@umdnj.edu

NJ Pediatric Reference Range(Absolute CD4)

156668960 - Adult286090024-603600102012-24410013559-12460016904-9511014600-4

CD495th

CD45th

Age inMonths

NJ Pediatric Reference Range(CD4%)

593360 - Adult513524-60543112-2458349-1261364-964410-4

CD4%95th

CD4 %5th

Age inMonths

NICHD -Mofenson etal. early 1990s

HIV Pediatric Prognostic MarkersCollaborative Study Group

• Meta analysis– 3941 children enrolled

• 8 cohort studies• 9 randomized trials in Europe / US

• Estimates of risk are derived from parametricsurvival models

• http://www.ctu.mrc.ac.uk/penta/hppmcs/default.htm

0

20

40

60

80

100

0 5 10 15 20 25 30 35 40 45 50

CD4 percent

Prob

abili

ty o

f AID

S (%

)

6 months1 year2 years5 years10 years

Probability of AIDS within 12 months

HIV Paediatric Prognostic Markers Collaborative Study – Lancet 2003

Probability of death within 12 months

HIV Paediatric Prognostic Markers Collaborative Study

0

20

40

60

80

100

0 5 10 15 20 25 30 35 40 45 50

CD4 percent

Prob

abili

ty o

f dea

th (%

)

6 months1 year2 years5 years10 years

Supported by AAAAI, NIAID, NICHD

WT Shearer, HM Rosenblatt, RS Gelman,R Oyomopito, S Plaeger, ER Stiehm,DW Wara, SD Douglas, K Luzuriaga,

EJ McFarland, R Yogev, MH Rathore,W Levy, BL Graham, SA Spector

LYMPHOCYTE SUBSETS INHEALTHY CHILDREN

FROM BIRTH THROUGH18 YEARS OF AGE:

THE PACTG P1009 STUDY

PEDIATRIC IMMUNOLOGYCORE LABORATORIES (PICLs)

Baylor College of Medicine / TexasChildren’s Hospital (TCH)

Children’s Hospital of Philadelphia (CHOP)

University of California, Los Angeles(UCLA)

University of California, San Diego (UCSD)

University of California, San Francisco(UCSF)

University of Colorado

University of Massachusetts

Observational, Cross-Section of HIV-Noninfected/HIV-Nonexposed Children

Well Children: No Rx Meds, Pregnancy,Acute Infections

7 Age Strata: 0-3 mos, 3-6 mos, 6-12mos; 1-2 yrs; 2-6 yrs, 6-12 yrs, 12-18yrs (non-overlapping)

Up to 120 Children Per Age Stratum:851 Total Enrollment

Racial/Ethnic Mix Similar to That ofPACTG Study Patients

METHODS: STUDY DESIGN,ELIGIBILITY, SAMPLE SIZE

Age Categories3-6 mos0-3 mos 6-12 mos 1-2 yrs 2-6 yrs 12-19 yrs6-12 yrs

Cou

nts

1000

2000

3000

4000

5000

6000

P1009: CD4 Count0

Age Categories3-6 mos0-3 mos 6-12 mos 1-2 yrs 2-6 yrs 12-19 yrs6-12 yrs

Perc

ent

2030

4 05 0

6 07 0

P1009: CD4 Percent

Age Categories

6066

0

Perc

ent

010

2030

4050

Age Categories3-6 mos0-3 mos 6-12 mos 1-2 yrs 2-6 yrs 12-19 yrs6-12 yrs

P1009: CD3+CD4+CD45RO+ PERCENT

Age: Highly Significant

PICL: Highly Significant

Race/Ethnicity: Much Less So

Gender: Much Less So

RESULTS: REGRESSIONANALYSIS/SIGNIFICANTVARIABLES

Pediatric CD4 Technology Issues

• Dual Platform• Single Platform• Suitable for different settings• Technology Transfer• Cost / test• Sustainability

Guyana

Burkina Faso

PointCARE System

Hematology/Flow Cytometry for HIV/AIDS PatientCare in Decentralized Settings

Closed-Tube Operation –Loading/Cap Piercing

Patient sample and reagents bar-code are tracked in the instrument.

4. Lysing Reagent Tube or Cleaning Solution Tube

3. Rinse Tube

2. CD4 Reagent Tube

1. Patient Whole Blood Sample Tube

Automated Patient Results –No operator data interpretation

0

200

400

600

800

1000

1200

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

Cou

nts CD 4 ABS

CD 8 ABS

CD4% CD4 Absolute CD8% CD8 AbsoluteSD 1.122943 22 1.988587 31Mean 22.52 350.34 58.49 918.31Median 22.65 355.29 58.83 923.63Max 24.60 386.22 60.77 954.09Min 17.63 276.79 49.25 773.23

31 Replicates Same Tech

CD4 AbsoluteSamples Acquired on Day 1 and Day 2

(Same stained sample)

171

286

255

166

269254

050

100150200250300350

Sample 1 Sample 2 Sample 3

CD

4 C

ount

Day 1Day 2

Samples Acquired on Machine 1 and Machine2

(Different stained sample)Tech 1

0

500

1000

1500

2000C

D4

Cou

nt

Machine 1

Machine 2

Tech 2

0

200

400

600

800

1000

1200

1400

1600

CD4 C

ount Machine 1

Machine 2

Guyana – FACSCount10 Samples in Triplicate

(CV’s are displayed above replicates)

0

100

200

300

400

500

600

700

1 2 3 4 5 6 7 8 9 10

4.57

18.29

2.99

0.65

18.12

5.236.23

3.39

4.084.57

Abs

olut

e C

D4 Mean CV = 6.81%

October 2004