Lipopeptide Immunisation With GTU-multiHIV Trial
The combination of GTU-MultiHIV B DNA and LIPO-5 vaccines in a prime-boost strategy is expected to induce strong and diverse HIV-specific immune responses in HIV-infected patients. The investigators will carry out the clinical therapeutic immunization "proof of concept" trial in HIV infected patients. The investigators propose a multi-center double blind randomized versus placebo phase II clinical trial in patients who are chronic asymptomatic HIV-infected patients, with undetectable viral load while treated with a potent combination of antiviral drugs. Patients will continue antiviral therapy combined with either therapeutic vaccination or placebo vaccination. Patients will undergo the procedure which includes a prime with the GTU-MultiHIV B DNA vaccine or placebo administered by IM injections via Biojector (a needle-free injection system) followed by a boost of LIPO-5 vaccine or placebo also given IM.
In total, 105 HIV-1 patients will be enrolled: 35 in the placebo arm and 70 in the vaccine arm. Patients will receive antiretroviral treatments and 3 administrations of DNA vaccine or its placebo at weeks 0, 4 and 12 (corresponding to prime vaccinations). They also receive 2 doses of LIPO-5 vaccines or its placebo at week 20 and 24 (corresponding to boost vaccinations). At week 36 antiretroviral treatments will be interrupted until week 48. Patients will be intensely monitored during the treatment interruption period. After start of cART treatment (at the latest in W48), a data collection from clinical car will be carried out. A blood sample with W74 will allow to study the persistence ot the immunizing responses, 1 year after the injection of the last vaccine/placebo.
The primary efficacy endpoint is a plasma HIV-1 RNA level at week 48 (e.g. 12 weeks after stopping all antiviral treatment).
The main hypothesis for conducting a phase II randomized trial is that immune responses in vaccinated patients may be associated with a better control of viral replication following c-ART interruption as compared to placebo-vaccinated patients.
|HIV-1 Infection||Biological: Placebos of GTU-multiHIV B and LIPO-5 vaccines Biological: GTU-multHIV B vaccine and LIPO-5 vaccine||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Evaluation of a Therapeutic Immunization Strategy Associating a DNA Vaccine (GTU-MultiHIV B) Followed by a Lipopeptide Vaccine (LIPO-5) in the Control of Viral Replication Following Antiretroviral Treatment Interruption in HIV-1 Infected Patients With a CD4 Cell Count ≥ 600/mm3|
- Plasma HIV-1 RNA level [ Time Frame: week 48 (W48) ]
- Plasma HIV-RNA after stopping antiviral treatment [ Time Frame: W40, W44, W48 and W74 ]
- Percentage of patients with plasma HIV-RNA below 10 000 copies/mL [ Time Frame: W48 ]
- Ultrasensitive proviral DNA [ Time Frame: W-3, W20, W32 and W44 ]
- CD4 T cell counts [ Time Frame: W40, W44 and W48 or prior HAART resumption and W74 ]
- Percentages of patients who resumed HAART [ Time Frame: between W36 and W48 ]
- Percentages of patients who reached CD4 cell counts < 350/mm3 confirmed two weeks apart [ Time Frame: between W36 and W48 ]
- Strength of HIV-specific CD4/CD8 responses [ Time Frame: W0, W16, W28, W48 or at the time of failure anw W74 ]
- Proportion of responders to at least one HIV peptide pool [ Time Frame: W0, W16, W28, W48 or at the time of failure and W74 ]
- Breadth of CD4/CD8+ HIV-specific responses defined as the number of HIV pools recognized among the 18 pools [ Time Frame: W0, W16, W28, W48 or at the time of failure and W74 ]
- Polyfunctionality of HIV specific T cell responses evaluated by the mean proportion of CD4/CD8+ T cells producing IL-2 and/or IFN-g following ex-vivo stimulation with HIV-1 peptide pools [ Time Frame: W0, W16, W28, W48 and W74 ]
- Adverse Events > grade 2 [ Time Frame: W0, W4, W12, W16, W20, W24, W28, W32, W36, W38, W40, W42, W44, W48 and W74 ]
- AIDS-defining events and serious non-AIDS events defined as cardiovascular diseases, kidney diseases, end stage liver diseases, non-AIDS defining malignancies except basal cellular skin cancer, and bacterial infections [ Time Frame: W0, W4, W12, W16, W20, W24, W28, W32, W36, W38, W40, W42, W44, W48 and W74 ]
- Analysis of predictive factors for plasma HIV-RNA [ Time Frame: W48 ]
|Study Start Date:||July 2013|
|Estimated Study Completion Date:||October 2017|
|Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Placebo Comparator: Vaccine placebos
Vaccine placebos corresponding to the dilutant of these vaccines
Biological: Placebos of GTU-multiHIV B and LIPO-5 vaccines
Placebos corresponds respectively to 1X PBS pH = 7.2 and glucose 5%
|Experimental: Vaccine arm||
Biological: GTU-multHIV B vaccine and LIPO-5 vaccine
Vaccines are respectively an HIV-DNA plasmid and a mixture of 5 HIV-lipopeptides.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01492985
|Service d'Immunologie clinique, Centre de vaccination anti-VIH ANRS Mondor Ile-de-France, Hôpital Henri Mondor|
|Créteil, France, 94010|
|Principal Investigator:||Yves Lévy, PU-PH||Hôpital Henri Mondor - Créteil - France|
|Study Director:||Geneviève Chêne, PU-PH||CMG-EC de l'INSERM U897 / ANRS|