Transcript Overview Pediatric HIV Program & IMPAACT/PACTG Vaccine

Overview Pediatric HIV Program &
IMPAACT/ PACTG Vaccine Research
Children’s National Medical Center,
Washington, DC
Dr.Hans ML Spiegel
Director Special Immunology Service/Division of Infectious
Disease
Children’s National Medical Center
[email protected]
202-884-2980
Special Immunology Service
Children’s National Medical Center
Washington, D.C.
Special Immunology Service (SIS)
 Comprehensive Infectious Disease Service
and Ambulatory Service based program for
infants and children with HIV infection and
services for HIV exposed infants and children
at-risk for HIV infection.
 The SIS Clinic provides multi-disciplinary
care for 170 HIV positive infants and
children (96% African American, 4%
hispanic, caucasian and other ethnicity)
 Further annual evaluation of more than 150
infants with perinatal HIV exposure.
Burgess Clinic
Children’s National Medical Center
Washington, D.C.
HIV Infected Youth in Care
Burgess Clinic, Washington, D.C.
149 patients with HIV infection
80 (54%) female; 69 (46%) male
81 (54%) acquired infection perinatally
Perinatally infected teens are now
largest source of new patients
72 (48%) now defined as having AIDS
Age Distribution Children & Youth
With HIV-1 Infection
At CNMC September 2006
30
25
20
15
n=PTs
10
5
0
1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5
0- 1- 2- 3- 4- 5- 6- 7- 8- 9-1 0-1 1-1 2-1 3-1 4-1 5-1 6-1 7-1 8-1 9-2 0-2 1-2 2-2 3-2 4-2
1 1 1 1 1 1 1 1 1 1 2 2 2 2 2
Years
100
CD4+ T-Lymphocyte Subset Distribution All
Patients With HIV-1 Infection CNMC,
September 2006
80
58.8
60
% of PTs
40
20
26.5
14.6
0
0-15%
>15 -25%
>25%
CD4 T-Lymphocyte Subset % Range
Ethnicity Of Children & Youth With HIV-1
Infection at CNMC, September 2006
8.80%
2.80%
2%
1.20%
0.40%
84.80%
African American
African
Hispanic
Mixed Race
Caucasian
Asian
% of Patients
Most Recent HIV RNA Viral Load
Range of Pediatric Patients (N=301)
45%
40%
35%
30%
25%
20%
15%
10%
5%
0%
39%
27%
26%
13%
VL<400
VL 40010000
VL 10000100000
VL >
100000
HIV-1 Plasma RNA Viral Load Strata
HIV Resistance Testing by Genotype or
Phenotype All Age Groups (0-24 Years)
 162 of 301 active Patients (53.8%) had
HIV Resistance testing by Phenotype
or virtual Phenotype
 150 of 301 active Patients (49.8%) had
HIV resistance testing by Genotype
160
140
120
100
80
60
40
20
0
Clade B
(95.1%)
Clade A (2.1%)
Clade B (95.1%)
Clade A
(2.1%)
Clade C
(2.8%)
Genotyping Result
(n=139)
Clade C (2.8%)
Country Of Origin Recent Immigrant
Children With HIV Infection
• Nigeria
• Ethiopia
• South Africa
• Tanzania
• Zambia
• Sierra Leone
• Cameroon
• Ivory Coast
• Kenya
CDC Pediatric HIV Classification/
Clinical Categories (1994 Revised)
CATEGORY N: Not Symptomatic
Children with no signs/symptoms OR
One sign/symptom in Category A
CATEGORY A: Mildly Symptomatic
Two or more of the following:
Lymphadenopathy; Hepatomegaly; Splenomegaly;
Dermatitis; Parotitis; Recurrent/persistent
URIs/sinusitis/otitis
CATEGORY B: Moderately Symptomatic
HIV-related signs/symptoms not in Category A/C
CATEGORY C: Severely Symptomatic
AIDS-defining disease (except LIP, which is CDC-B)
CDC CLASSIFICATIONS
(% of CNMC Patients)
N1, 5.4
N2
N2, 4.2
C3, 21.1
A1, 9
A2, 3.6
C2, 4.8
C1, 0
B3, 24.7
N1
A3, 3
B1, 8.4
B2, 15.7
A1
A2
A3
B1
B2
B3
C1
C2
C3
Immune Based Therapy Transdermal
DNA Dendritic Cell Vaccine For
Children with HIV Infection
 Dr. Julianna Lisziewicz et al. (Genetic
Immunity ) have developed a novel shuttle
system (DermaVirTM ) for the administration
of DNA vaccines.
 DNA vaccine in solution with
polyethylenimine (PEI) mannose (PEIm) is
applied to the surface of the skin, to target
the mannose receptor of Langerhans cells
(LC).
STI-HAART does not Induce Immune
Control during Treatment Interruptions in
Macaques with AIDS
10,000,000
SIV RNA (copies/mL)
Median
1,000,000
100,000
10,000
Lisziewicz J et al.
1,000
HAART
HAART
HAART
HAART
HAART
HAART
HAART
100
0
HAART
28 49 70 91 113 133 161 182 203 224 245 266 287
HAART HAART HAART TREATMENT TIME (Days)
DermaVir + STI-HAART Induces Immune
Control in Macaques with AIDS
Lisziewicz J et al.
IMPAACT P1049
A PHASE I/II STUDY OF THE SAFETY,
TOLERABILITY AND IMMUNOGENICITY OF A
TOPICAL THERAPEUTIC DNA DENDRITIC
CELL VACCINE (DERMAVIR PATCH) IN
CHILDREN, ADOLESCENTS AND YOUNG
ADULTS WITH HIV-1 INFECTION ON HIGHLY
ACTIVE ANTIRETROVIRAL THERAPY
(HAART)
Study Chair: Dr. Hans Spiegel
Pediatric Dermavir Vaccine Trial
DESIGN:
SAMPLE SIZE:
Phase I/II, age stratified, dose finding, open
label trial
32 evaluable subjects
 POPULATION: HIV-1 infected children ≥6 years to <13
years and Adolescents/young adults ≥13 years to <24 years
and
 CDC clinical category N, A, B, C (excluding subjects with
acute CDC-C complications) and
 Documented CD4(+) T-cell count of ≥20% and ≥350 cells/mm3
 HIV-1 RNA viral load <400 copies/mL for at least 12 months
 Stable HAART regimen (drugs of at least 2 different classes)
without interruptions for at least 6 months prior to study
entry. Treatment regimen changes for dosing convenience and
in response to toxicity are permitted.
STRATIFICATION Groups will be sequentially enrolled.
The number of subjects aged 21-<24, will be limited to no
more than 25% of the group that will be stratified as
adolescents/young adults ≥13 years to <24 years.
DermaVir, a DNA vaccine for topical administration will be
administered in the following doses (vaccine standard unit
per patch: 0.1 mg DNA = 0.8 mL of DermaVir vaccine;
patch size is 80 cm2):
Group A (low dose – 0.1 mg), 1 patch per vaccination day, on
Day 0, 42, and 84 (adolescents/young adults first)
Group B (medium dose – 0.4 mg), 4 patches per vaccination
day, on Day 0, 42, and 84
Group C (high dose – 0.4 mg), 4 patches per vaccination day,
on Day 0, 7, 42, 49, 84, and 91