Dermal HIV-1 Immunization During Anti-retroviral Therapy Followed by Repeated Treatment Interruptions
- Conditions
- HIV-1
- Registration Number
- NCT01140139
- Lead Sponsor
- Swedish Institute for Infectious Disease Control
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
Trial Locations
- Locations (1)
South Hospital
🇸🇪Stockholm, Sweden
South Hospital🇸🇪Stockholm, Sweden