Dermal HIV-1 Immunization During Anti-retroviral Therapy Followed by Repeated Treatment Interruptions (Vac09)

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1
• Intervention / Treatment: Biological: HIV DNA Vaccine

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 1188
    • South Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged between 18 and 60 years
2. 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.
3. HIV infection detected by two serological and/or HIV plasma RNA tests
4. On HAART for at least 6 months with less than 50 copies/ml of plasma HIV-1 RNA at two determinations over 3 months
5. Current CD4 count above 400
6. CD4 count nadir >200
7. Viral isolate pre ART available is preferable but not mandatory
8. Willing to consider stopping HAART repeatedly.
9. Willing to conform to a low alcohol intake (maximum of one glass per day)
10. Able to tolerate didanosine and hydroxyurea
11. Willing to change their HAART to exclude NNRTI and stavudine
12. Able to give informed consent
13. Availability for follow-up for planned duration of the study

Exclusion Criteria:

1. Patients with ongoing infection(s) other than HIV.
2. Prior or current pancreatitis or history of alcohol abuse.
3. Ongoing neuropathy and history of more than grade 1 neuropathy.
4. History of mutations to more than one class of anti-retroviral drugs or switched drugs more than once due to failure.
5. Sun or solarium exposure at the immunizing sites one month before or during the trial.
6. Cortisone treatment, systemic or local at the immunizing sites, one month before or during the trial.
7. Patients with signs of autoimmune diseases
8. Patients with creatinine > 2mg/dl, Hb < 12g/dl, leukocytes < 3,000ul, platelets <150,000/ul and LFT > 5x upper limit of normal
9. Patients on any immune modulating or investigational drug
10. Anamnestic allergy to kanamycin, plasmid gene products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIV DNA + Hydroxyurea; 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; 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.
Experimental: HIV DNA; 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; 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.
Placebo Comparator: Placebo; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description
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
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

Collaborators and Investigators

• Sponsor: Swedish Institute for Infectious Disease Control
• Collaborators: The Swedish Research Council; European Union; Läkare mot AIDS Forskningsfond

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: June 7, 2010
• First Submitted That Met QC Criteria: June 8, 2010
• First Posted (Estimate): June 9, 2010

Study Record Updates

• Last Update Posted (Estimate): June 9, 2010
• Last Update Submitted That Met QC Criteria: June 8, 2010
• Last Verified: February 1, 2006

More Information

Terms related to this study

• Other Study ID Numbers: DermHIVImm

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No