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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]
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