Dermal HIV-1 Immunization During Anti-retroviral Therapy Followed by Repeated Treatment Interruptions

Study Overview
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Brief Summary
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In this study, the investigators evaluated a therapeutic HIV-1 DNA vaccine administered with a novel topical application method to 12 chronically HIV-infected cART treated patients. The HIV DNA plasmids used in this study encode for envelope gp160 of HIV-1 subtypes A, B and C, rev B, Gag A and B and reverse transcriptase (RT) B. The patients were randomly assigned to three groups; group 1 (n=4) were immunized six times with 0.4 mg of HIV DNA plasmids topically, group 2 (n=4) were immunized six times with 0.4 mg of HIV DNA plasmids topically and treated with 500 mg of hydroxyurea daily until visit 10, group 3 (n=4) four patients received placebo. The immunization was performed during three cycles of 7 weeks of cART followed by four weeks of therapy interruption. After the last cycle of cART the patients were maintained on a definitive treatment interruption until CD4+ T cell counts dropped below 350/ mm3 at two time points. Cellular and humoral immune responses, viral load and CD4+ T a cell count was analysed throughout the study.

Official Title
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Active Immunotherapy Against HIV During Highly Active Anti-retroviral Therapy Followed by Repeated Treatment Interruptions

Conditions
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HIV-1

Intervention / Treatment
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* Biological: HIV DNA Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 and 60 years Female, who is documented infertile or in menopause since at least 1 year, or male, who are willing not father a child for the duration of the study. HIV infection detected by two serological and/or HIV plasma RNA tests On HAART for at least 6 months with less than 50 copies/ml of plasma HIV-1 RNA at two determinations over 3 months Current CD4 count above 400 CD4 count nadir >200 Viral isolate pre ART available is preferable but not mandatory Willing to consider stopping HAART repeatedly. Willing to conform to a low alcohol intake (maximum of one glass per day) Able to tolerate didanosine and hydroxyurea Willing to change their HAART to exclude NNRTI and stavudine Able to give informed consent Availability for follow-up for planned duration of the study Exclusion Criteria: Patients with ongoing infection(s) other than HIV. Prior or current pancreatitis or history of alcohol abuse. Ongoing neuropathy and history of more than grade 1 neuropathy. History of mutations to more than one class of anti-retroviral drugs or switched drugs more than once due to failure. Sun or solarium exposure at the immunizing sites one month before or during the trial. Cortisone treatment, systemic or local at the immunizing sites, one month before or during the trial. Patients with signs of autoimmune diseases Patients with creatinine > 2mg/dl, Hb < 12g/dl, leukocytes < 3,000ul, platelets <150,000/ul and LFT > 5x upper limit of normal Patients on any immune modulating or investigational drug Anamnestic allergy to kanamycin, plasmid gene products

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV DNA + Hydroxyurea<br>0.4 mg of DNA plasmids encoding HIV env A, B, C and Rev B, gag A, B and RT mut formulated in PEI and glucose was applied topically with the DermaPrep procedure six times during cycles of 7 weeks of active HAART. Every immunization cycle was followed by four weeks of therapy interruption. The patients also received 500 mg of hydroxyurea daily. | Biological: HIV DNA Vaccine<br>* 0.4 mg of DNA plasmids encoding HIV env A, B, C and Rev B, gag A, B and RT mut formulated in PEI and glucose was applied topically with the DermaPrep procedure six times during cycles of 7 weeks of active HAART. Every immunization cycle was followed by four weeks of therapy interruption.<br>|
| Experimental: HIV DNA<br>0.4 mg of DNA plasmids encoding HIV env A, B, C and Rev B, gag A, B and RT mut formulated in PEI and glucose was applied topically with the DermaPrep procedure six times during cycles of 7 weeks of active HAART. Every immunization cycle was followed by four weeks of therapy interruption. | Biological: HIV DNA Vaccine<br>* 0.4 mg of DNA plasmids encoding HIV env A, B, C and Rev B, gag A, B and RT mut formulated in PEI and glucose was applied topically with the DermaPrep procedure six times during cycles of 7 weeks of active HAART. Every immunization cycle was followed by four weeks of therapy interruption.<br>|
| Placebo Comparator: Placebo<br>PEI and glucose was applied topically with the DermaPrep procedure six times during cycles of 7 weeks of active HAART. Every immunization cycle was followed by four weeks of therapy interruption. | Biological: HIV DNA Vaccine<br>* 0.4 mg of DNA plasmids encoding HIV env A, B, C and Rev B, gag A, B and RT mut formulated in PEI and glucose was applied topically with the DermaPrep procedure six times during cycles of 7 weeks of active HAART. Every immunization cycle was followed by four weeks of therapy interruption.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and feasibility | The safety and feasibility of dermal HIV-1 DNA vaccination will be evaluated by recording all medical events. They will be graded as to their seriousness, severity and relationship to the immunization. Plasma HIV-1 RNA levels and T-cell levels will be closely monitored. In addition to this the patient's individual experience and quality of life will be assessed. |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment effects | To evaluate whether dermal HIV-1 DNA vaccination can prolong periods without treatment in HIV-infected individuals. This will be evaluated by structured treatment interruption with close monitoring of HIV viral load and CD4+ T cell counts |  |