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

NCT ID: NCT01140139

Last Updated: 2010-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2009-12-31

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.

Conditions

HIV-1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

HIV DNA Vaccine

Intervention Type: BIOLOGICAL

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.

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.

Group Type: EXPERIMENTAL

HIV DNA Vaccine

Intervention Type: BIOLOGICAL

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

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.

Group Type: PLACEBO_COMPARATOR

HIV DNA Vaccine

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Union

OTHER

Sponsor Role: collaborator

The Swedish Research Council

OTHER_GOV

Sponsor Role: collaborator

Läkare mot AIDS Forskningsfond

UNKNOWN

Sponsor Role: collaborator

Swedish Institute for Infectious Disease Control

OTHER

Sponsor Role: lead

Responsible Party

Karolinska Institute and South Hospital, Stockholm

Locations

South Hospital

Stockholm, , Sweden

Countries

Sweden

Other Identifiers

DermHIVImm

Identifier Type: -

Identifier Source: org_study_id