Safety and Tolerability of a Therapeutic DNA Dendritic Cell Vaccine in HIV-Infected Children, Adolescents, and Young Adults

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)

The therapeutic DNA vaccine, DermaVir, represents an immunization strategy that targets lymph node dendritic cells. Because of the high percentage of naive CD4 cells in children and adolescents, the potential for effective new HIV-specific CD4 cell responses may be more achievable in children than in adults. The primary purpose of this study is to evaluate the safety and tolerability of DermaVir in children and young adults.

The introduction of highly active antiretroviral therapy (HAART) for children and adolescents has resulted in improved control of viral replication for prolonged periods of time and a significant reduction in morbidity. However, when compared to the responses seen in adults, children have overall inferior virologic responses. The therapeutic vaccine, DermaVir, represents an immunization strategy that targets lymph node dendritic cells. Because of the high percentage of naive CD4 cells in children and adolescents, the potential for effective new HIV-specific CD4 cell responses may be more achievable in children than in adults. The primary purpose of this study is to evaluate the safety and tolerability of DermaVir in children and young adults.

This study will last up to 61 weeks (up to 13 weeks of treatment with an additional 48 weeks for follow-up). Participants will be randomly stratified according to age and dosage. Group 1 will consist of 8 adolescents and young adults (between ages 13 and 23) and 8 children (between ages 6 and 12). Group 1 participants will have one 0.8 ml DermaVir patch and one control patch applied on Days 0, 42, and 84. Group 2 will consist of 4 adolescents and young adults and 4 children. Group 2 participants will have four 0.8 ml DermaVir patches applied on Days 0, 42, and 84. Group 3 will consist of 4 adolescents and young adults and 4 children. Group 3 participants will have four 0.8 ml DermaVir patches applied on Days 0, 7, 42, 49, 84, and 91.

There will be 14 study visits for each participant. They will occur at screening and Days 0, 7, 21, 42, 49, 63, 84, 91, 105, 126, 168, 259, and 427. Screening will occur up to 30 days before the first vaccination (Day 0). Medical history and physical exam will occur at all visits. Blood and urine collection and an adherence assessment will occur at most visits. A urine pregnancy test will occur for females at most visits.

Inclusion Criteria:

• HIV infected
• Receiving HAART consisting of drugs from at least 2 different classes for at least 12 months prior to study entry
• CD4 count of 350 cells/mm3 or greater
• Viral load less than 400 copies/ml for at least 12 months prior to screening
• If female, agree to avoid pregnancy and use two methods of contraception. More information on this criterion can be found in the protocol.
• If male, agree to avoid attempting to impregnate a female and not participate in sperm donation programs. Male participants must agree to use a condom during sexual activity from the date of receipt of the first study vaccination until 6 months after receipt of the last study vaccination.

Exclusion Criteria:

• Failing antiretroviral regimen
• Skin diseases, including active atopic dermatitis, active or history of psoriasis, active urticaria, known hypersensitivity to adhesive tape, history of keloid, and active or history of vitiligo
• Tattoos or changes in pigment at selected skin vaccination sites
• Hair or tattoo removal in close proximity to vaccine site on skin
• Acute or chronic illness. More information on this criterion can be found in the protocol.
• Chronic autoimmune disease, clinically significant bleeding disorder, or insulin dependent diabetes mellitus
• Clinical toxicity (Grade 2 or greater) at screening
• Prior treatment with any HIV vaccine
• Treatment with any HIV immune modulating agents or chemotherapy for malignancy within 12 months of study entry
• Vaccinations within 28 days of study entry
• Participation in an investigational new drug protocol within 60 days prior to screening
• Systemic steroid therapy within 28 days of study entry
• Abnormal laboratory values. More information on this criterion can be found in the protocol.
• Excessive exposure to the sun
• Breastfeeding or pregnant