Antiretroviral-Sparing Concept With HIV-specific T Cell Precursors With High Proliferative Capacity (PHPC)

Study Overview
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Brief Summary
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PHPC-02 is a phase II, randomized, placebo-controlled trial designed to investigate whether therapeutic immunization during highly active antiretroviral therapy (HAART) induces elevations of HIV-specific T cell precursors with high proliferative capacity (PHPC) in HIV-1-infected individuals, and whether the quantity of PHPC correlates with the viral load set point following analytical treatment interruption (ATI). Subjects will be randomized to receive either DermaVir Patch (8 subjects per cohort) or DermaVir Patch Placebo (8 subjects per cohort) every four weeks for three applications while receiving maximally suppressive HAART. HAART will be discontinued at Week 9 for an ATI period of 20 weeks.

Detailed Description
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16 subjects on maximally suppressive HAART were randomized to receive three doses of either DermaVir or Placebo immunotherapy. Subjects receive three DermaVir/Placebo treatments over eight weeks (Weeks 0, 4 and 8) while receiving HAART. HAART is discontinued for a 20 week ATI. Resumption of HAART during ATI is subjects experience: A confirmed CD4+ cell decrease by > 50% A confirmed CD4+ cell decrease to less than 350 counts/mL A confirmed VL increase > 300,000 copies Emergence of CDC AIDS related event(s) Signs or symptoms of clinically significant immunosuppression The subject or the subject's clinician wishes to restart HAART The subject becomes pregnant

Official Title
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Antiretroviral-Sparing Concept: An Exploratory Phase II, Randomized, Single Blind Placebo-Controlled Study to Investigate the Effect of Therapeutic Immunization on the Quantity of HIV-Specific T Cell Precursors During Highly Active Antiretroviral Therapy Followed by Analytical Treatment Interruption

Conditions
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HIV Infection

Intervention / Treatment
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* Biological: DermaVir
* Biological: Placebo
* Drug: HAART


Participation Criteria
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Eligibility Criteria
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Main inclusion Criteria: HIV-1 infection On a non-hydroxyurea based HAART for at least one year Pre-HAART CD4 nadir > 250 cells/mm3 Pre-HAART viral load > 5,000 copies/mL Undetectable viral load for the six month period preceding the study CD4 T-cell count >500 cells/mm3 for the six month period preceding the study Main exclusion Criteria: No skin disease No hypersensitivity to adhesive tape or Tegaderm No history of keloid No history of vitiligo, melasma, skin cancer No tattoos or changes in pigment at the skin treatment sites No autoimmune diseases No hepatitis B, C coinfections

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DermaVir + HAART<br>Dosage: 0.4 mg DNA Dosage form: 3.2 mL DNA/PEIm nanomedicine Administration with 4 DermaPrep patches Frequency: every 4 weeks Duration: 8 weeks (3 DermaVir treatments) | Biological: DermaVir<br>* DermaVir is a synthetic nanomedicine. The active pharmaceutical ingredient is a single plasmid DNA expressing 15 HIV proteins that assemble to HIV-like particles. DermaVir is topically administered with DermaPrep medical device to target the nanomedicine to Langerhans cells of the skin.These Langerhans cells migrate to the lymph node to induce cytotoxic T cells that can kill HIV-infected cells<br>* Other names: LC002;Drug: HAART<br>* Three or more antiretroviral drugs that can fully suppress HIV RNA<br>* Other names: Highly active antiretroviral therapy;|
| Placebo + HAART<br>Dosage form: 3.2 mL Placebo Administration with 4 DermaPrep patches Frequency: every four weeks Duration: 8 weeks (3 Placebo treatments) | Biological: Placebo<br>* Dextrose/glucose solution<br>* Other names: LC002 Placebo;Drug: HAART<br>* Three or more antiretroviral drugs that can fully suppress HIV RNA<br>* Other names: Highly active antiretroviral therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-specific memory T cells measured as PHPC count | DermaVir-induced PHPC count compared to Placebo | 9 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-1 RNA | HIV-1 RNA set-point after analytical treatment interruption | weeks 16 and 20 | 
| CD4+ and CD8+ T cell counts |  | 20 weeks | 
| Adverse Events |  | 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Vaccine, Immune Therapy, DermaVir, Treatment experienced