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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