Clinical trial NCT01140139: Dermal HIV-1 Immunization During Anti-retroviral Therapy Followed by Repeated Treatment Interruptions
Official title: Active Immunotherapy Against HIV During Highly Active Anti-retroviral Therapy Followed by Repeated Treatment Interruptions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1
Lead sponsor: Swedish Institute for Infectious Disease Control
Sponsor class: OTHER
Collaborators: name: European Union
name: The Swedish Research Council
name: Läkare mot AIDS Forskningsfond
First posted: 2010-06-09
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety and feasibility
Secondary outcomes:
measure: Treatment effects
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: South Hospital
Study officials:
References: