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

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

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

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)

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 (DermaVir TM ) 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 Lisziewicz J et al.

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: Phase I/II, age stratified, dose finding, open label trial SAMPLE SIZE: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.

STRATIFICATIONGroups 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