Overview Pediatric HIV Program & Overview Pediatric HIV Program & IMPAACT/ PACTG Vaccine ResearchIMPAACT/ PACTG Vaccine Research Children’s National Medical Center,Children’s National Medical Center,

Washington, DCWashington, DCDr.Hans ML SpiegelDr.Hans ML Spiegel

Director Special Immunology Service/Division of Infectious Director Special Immunology Service/Division of Infectious DiseaseDisease

Children’s National Medical CenterChildren’s National Medical Center

HSpiegel@cnmc.orgHSpiegel@cnmc.org202-884-2980202-884-2980

Special Immunology ServiceSpecial Immunology ServiceChildren’s National Medical CenterChildren’s National Medical Center

Washington, D.C.Washington, D.C.

Special Immunology Service (SIS)Special Immunology Service (SIS) Comprehensive Infectious Disease Service Comprehensive Infectious Disease Service

and Ambulatory Service based programand Ambulatory Service based program for for infants and children with HIV infection and infants and children with HIV infection and services for HIV exposed infants and children services for HIV exposed infants and children at-risk for HIV infection.at-risk for HIV infection.

The SIS Clinic provides multi-disciplinary The SIS Clinic provides multi-disciplinary care for care for 170 HIV positive infants and 170 HIV positive infants and childrenchildren (96% African American, 4% (96% African American, 4% hispanic, caucasian and other ethnicity) hispanic, caucasian and other ethnicity)

Further annual evaluation of more than 150 Further annual evaluation of more than 150 infants with perinatal HIV exposure.infants with perinatal HIV exposure.

Burgess ClinicBurgess ClinicChildren’s National Medical CenterChildren’s National Medical Center

Washington, D.C.Washington, D.C.

HIV Infected Youth in CareHIV Infected Youth in CareBurgess Clinic, Washington, D.C.Burgess Clinic, Washington, D.C.

149 patients with HIV infection149 patients with HIV infection80 (54%)80 (54%) female; female; 6969 (46%)(46%) male male 81 (54%)81 (54%) acquired infection perinatally acquired infection perinatallyPerinatally infected teensPerinatally infected teens are now are now largest source of new patientslargest source of new patients72 (48%)72 (48%) now defined as having AIDS now defined as having AIDS

Age Distribution Children & Youth With HIV-1 Infection

At CNMC September 2006

0

5

10

15

20

25

30

Years

n=PTs

CD4+ T-Lymphocyte Subset Distribution All Patients With HIV-1 Infection CNMC,

September 2006

14.626.5

58.8

0

20

40

60

80

100

0-15% >15 -25% >25%

CD4 T-Lymphocyte Subset % Range

% of PTs

Ethnicity Of Children & Youth With HIV-1 Infection at CNMC, September 2006

84.80%

8.80%

2.80%

2%

1.20%

0.40%

African American

African

Hispanic

Mixed Race

Caucasian

Asian

Most Recent HIV RNA Viral Load Range of Pediatric Patients (N=301)

13%

26%27%

39%

0%5%

10%15%20%25%30%35%40%45%

VL<400 VL 400-10000

VL 10000-100000

VL >100000

HIV-1 Plasma RNA Viral Load Strata

% o

f P

atie

nts

HIV Resistance Testing by Genotype or HIV Resistance Testing by Genotype or Phenotype All Age Groups (0-24 Years)Phenotype All Age Groups (0-24 Years)

162 of 301162 of 301 active Patients active Patients (53.8%)(53.8%) had had HIV Resistance testing by Phenotype HIV Resistance testing by Phenotype or virtual Phenotypeor virtual Phenotype

150 of 301150 of 301 active Patients active Patients (49.8%)(49.8%) had had HIV resistance testing by GenotypeHIV resistance testing by Genotype

Clade A (2.1%)

Clade B (95.1%)

Clade C (2.8%)

0

20

40

60

80

100

120

140

160

Genotyping Result(n=139)

Clade A (2.1%)

Clade B (95.1%)

Clade C (2.8%)

Country Of Origin Recent Immigrant Country Of Origin Recent Immigrant Children With HIV InfectionChildren With HIV Infection

• Nigeria

• Ethiopia

• South Africa

• Tanzania

• Zambia

• Sierra Leone

• Cameroon

• Ivory Coast

• Kenya

CDC Pediatric HIV Classification/ CDC Pediatric HIV Classification/ Clinical Categories (1994 Revised)Clinical Categories (1994 Revised)

CATEGORY N:CATEGORY N: Not SymptomaticNot SymptomaticChildren with no signs/symptoms ORChildren with no signs/symptoms OROne sign/symptom in Category AOne sign/symptom in Category A

CATEGORY A:CATEGORY A: Mildly SymptomaticMildly SymptomaticTwo or more of the following:Two or more of the following:Lymphadenopathy; Hepatomegaly; Splenomegaly; Lymphadenopathy; Hepatomegaly; Splenomegaly; Dermatitis; Parotitis; Recurrent/persistent Dermatitis; Parotitis; Recurrent/persistent URIs/sinusitis/otitisURIs/sinusitis/otitis

CATEGORY B:CATEGORY B: Moderately SymptomaticModerately SymptomaticHIV-related signs/symptoms not in Category A/CHIV-related signs/symptoms not in Category A/C

CATEGORY C:CATEGORY C: Severely SymptomaticSeverely SymptomaticAIDS-defining disease (except LIP, which is CDC-B)AIDS-defining disease (except LIP, which is CDC-B)

CDC CLASSIFICATIONS (% of CNMC Patients)

N1, 5.4

N2, 4.2

A1, 9

A2, 3.6

A3, 3

B1, 8.4

B2, 15.7B3, 24.7

C1, 0

C2, 4.8

C3, 21.1

N1

N2

A1

A2

A3

B1

B2

B3

C1

C2

C3

Immune Based Therapy Transdermal Immune Based Therapy Transdermal DNA Dendritic Cell Vaccine For DNA Dendritic Cell Vaccine For

Children with HIV InfectionChildren with HIV Infection Dr. Julianna Lisziewicz et al. (Genetic Dr. Julianna Lisziewicz et al. (Genetic

Immunity ) have developed a novel shuttle Immunity ) have developed a novel shuttle system (DermaVirsystem (DermaVirTMTM ) for the administration ) for the administration of DNA vaccines. of DNA vaccines.

DNA vaccine in solution with DNA vaccine in solution with polyethylenimine (PEI) mannose (PEIm) is polyethylenimine (PEI) mannose (PEIm) is applied to the surface of the skin, to target applied to the surface of the skin, to target the mannose receptor of Langerhans cells the mannose receptor of Langerhans cells (LC).(LC).

STI-HAART does not Induce Immune STI-HAART does not Induce Immune Control during Treatment Interruptions in Control during Treatment Interruptions in

Macaques with AIDSMacaques with AIDS

Lisziewicz J et al.

DermaVir + STI-HAART Induces Immune DermaVir + STI-HAART Induces Immune Control in Macaques with AIDSControl in Macaques with AIDS

Lisziewicz J et al.

IMPAACT P1049IMPAACT P1049 A PHASE I/II STUDY OF THE SAFETY, A PHASE I/II STUDY OF THE SAFETY,

TOLERABILITY AND IMMUNOGENICITY OF TOLERABILITY AND IMMUNOGENICITY OF A TOPICAL THERAPEUTIC DNA DENDRITIC A TOPICAL THERAPEUTIC DNA DENDRITIC

CELL VACCINE (DERMAVIR PATCH) IN CELL VACCINE (DERMAVIR PATCH) IN CHILDREN, ADOLESCENTS AND YOUNG CHILDREN, ADOLESCENTS AND YOUNG

ADULTS WITH HIV-1 INFECTION ON HIGHLY ADULTS WITH HIV-1 INFECTION ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ACTIVE ANTIRETROVIRAL THERAPY

(HAART) (HAART)

Study Chair: Study Chair: Dr. Hans SpiegelDr. Hans Spiegel

Pediatric Dermavir Vaccine TrialPediatric Dermavir Vaccine TrialDESIGNDESIGN: : Phase I/II, age stratified, dose finding, Phase I/II, age stratified, dose finding,

open open label triallabel trialSAMPLE SIZESAMPLE SIZE:: 32 evaluable subjects32 evaluable subjects

POPULATIONPOPULATION:: HIV-1 infected children ≥6 years to <13 HIV-1 infected children ≥6 years to <13 years and Adolescents/young adults ≥13 years to <24 years years and Adolescents/young adults ≥13 years to <24 years andand

CDC clinical category N, A, B, C (excluding subjects with CDC clinical category N, A, B, C (excluding subjects with acute CDC-C complications) and acute CDC-C complications) and

Documented CD4(+) T-cell count of ≥20% and ≥350 cells/mm3Documented CD4(+) T-cell count of ≥20% and ≥350 cells/mm3 HIV-1 RNA viral load <400 copies/mL for at least 12 months HIV-1 RNA viral load <400 copies/mL for at least 12 months Stable HAART regimen (drugs of at least 2 different classes) Stable HAART regimen (drugs of at least 2 different classes)

without interruptions for at least 6 months prior to study without interruptions for at least 6 months prior to study entry. Treatment regimen changes for dosing convenience entry. Treatment regimen changes for dosing convenience and in response to toxicity are permitted.and in response to toxicity are permitted.

STRATIFICATIONSTRATIFICATION Groups will be sequentially enrolled. Groups will be sequentially enrolled. The number of subjects aged 21-<24, will be limited to no The number of subjects aged 21-<24, will be limited to no more than 25% of the group that will be stratified as more than 25% of the group that will be stratified as adolescents/young adults ≥13 years to <24 years.adolescents/young adults ≥13 years to <24 years.

DermaVirDermaVir, , a DNA vaccine for topical administration will be a DNA vaccine for topical administration will be administered in the following doses (vaccine standard unit administered in the following doses (vaccine standard unit per patch: 0.1 mg DNA = 0.8 mL of DermaVir vaccine; per patch: 0.1 mg DNA = 0.8 mL of DermaVir vaccine; patch size is 80 cm2):patch size is 80 cm2):

Group AGroup A (low dose – 0.1 mg), 1 patch per vaccination day, on (low dose – 0.1 mg), 1 patch per vaccination day, on Day 0, 42, and 84 (adolescents/young adults first)Day 0, 42, and 84 (adolescents/young adults first)

Group BGroup B (medium dose – 0.4 mg), 4 patches per vaccination (medium dose – 0.4 mg), 4 patches per vaccination day, on Day 0, 42, and 84day, on Day 0, 42, and 84

Group CGroup C (high dose – 0.4 mg), 4 patches per vaccination day, (high dose – 0.4 mg), 4 patches per vaccination day, on Day 0, 7, 42, 49, 84, and 91on Day 0, 7, 42, 49, 84, and 91