pediatric monitoring - cd4 issues in hiv diseasethomas n. denny new jersey medical school newark,...
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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, [email protected]
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NJ Pediatric Reference Range(Absolute CD4)
156668960 - Adult286090024-603600102012-24410013559-12460016904-9511014600-4
CD495th
CD45th
Age inMonths
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NJ Pediatric Reference Range(CD4%)
593360 - Adult513524-60543112-2458349-1261364-964410-4
CD4%95th
CD4 %5th
Age inMonths
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NICHD -Mofenson etal. early 1990s
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Age: Highly Significant
PICL: Highly Significant
Race/Ethnicity: Much Less So
Gender: Much Less So
RESULTS: REGRESSIONANALYSIS/SIGNIFICANTVARIABLES
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Pediatric CD4 Technology Issues
• Dual Platform• Single Platform• Suitable for different settings• Technology Transfer• Cost / test• Sustainability
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Guyana
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Burkina Faso
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PointCARE System
Hematology/Flow Cytometry for HIV/AIDS PatientCare in Decentralized Settings
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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
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Automated Patient Results –No operator data interpretation
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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
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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
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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
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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
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