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

NCT01140139 | Completed Phase 1 DMC

• 1 other identifier: DermHIVImm
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Treatment effects

Study Arms (3)

HIV DNA + Hydroxyurea

EXPERIMENTAL

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

HIV DNA

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

HIV DNA Vaccine 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; HIV DNA + Hydroxyurea; Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Swedish Institute for Infectious Disease Control: lead
• European Union: collaborator
• The Swedish Research Council: collaborator
• Läkare mot AIDS Forskningsfond: collaborator

Study Sites (1)

South Hospital

Stockholm, 1188, Sweden

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 7, 2010
• First Posted: June 9, 2010
• Study Start: September 1, 2006
• Primary Completion: October 1, 2009
• Study Completion: December 1, 2009
• Last Updated: June 9, 2010

Record last verified: 2006-02

Locations

SE (1)