Lipopeptide Immunisation With GTU-multiHIV Trial

ANRS, Emerging Infectious Diseases

Status and phase

Completed

Phase 2

Conditions

HIV-1 Infection

Treatments

Biological: Placebos of GTU-multiHIV B and LIPO-5 vaccines

Biological: GTU-multHIV B vaccine and LIPO-5 vaccine

Study type

Interventional

Funder types

Other

Identifiers

NCT01492985

ANRS 149 LIGHT (Other Identifier)

2009-018198-30

Details and patient eligibility

About

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.

Enrollment

103 patients

Sex

All

Ages

18 to 59 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria:

Documented HIV-1 infection (ELISA and Western blot)
Age ≥ 18 years and < 60 years
No history of CDC category C clinical events (1993), including cutaneous Kaposi's sarcoma
CD4 Nadir ≥ 300/mm3 Under antiretroviral treatment
CD4 ≥ 600/mm3 on all measurements within the previous 6 months* prior to W-3 screening visit (one single CD4 value between 550-600 cells/ mm3 is permitted)
CD4 value ≥ 600/ mm3 at W-3 screening visit
Plasma HIV1-RNA < 50 copies/mL on all measurements within the previous 6 months* (An occasional measurement of HIV-1 RNA (so-called " blip " between 50 and 200 copies/mL is permitted)
HIV1-RNA < 50 copies/mL at W-3 screening visit

* In the absence of measurement in the last 6 months, a measurement performed in the last 12 months is accepted
Treatment with a combination of antiviral drugs (cART) for at least 18 months regardless of the combination, under condition that :
- in the W24 visit the non-nucleoside inhibitors are replaced by a protease inhibitor potentiated by ritonavir
- no failure or resistance to the protease inhibitor was previously reported
With adequate method of contraception and negative pregnancy test (βHCG plasma) for women of childbearing potential
Laboratory parameters at W-3:
- polynuclear neutrophils ≥ 1,000/mm3
- haemoglobin ≥ 10 g/dl
- platelets ≥ 100,000/mm3
- creatinine ≤ 1.5 x N
- AST, ALT, bilirubin ≤ 2.5 x N
- proteinuria ≤ 1 g/L (++)
- anti-nuclear antibodies ≤ 1/320
- anticardiolipin antibodies ≤ 30 U
- no lupus anticoagulant
Participant agreeing to be treated and followed for at least 74 weeks according to the protocol
Participant agreeing to interrupt his/her cART treatment and, if applicable, to replace the non-nucleoside inhibitors by a protease inhibitor potentiated by ritonavir at W24
Participant agreeing to the use of condom, in particular during ART interruption period (between the visit S36 and the visite S48)
Participant covered by HealthInsurance (article L1121-11 of Code de la Santé Publique)
Written informed consent (at the latest the day of pre-inclusion and before all exams to be done in the context of the trial) (article L1122-1-1 of Code de la Santé Publique).

Exclusion criteria

Pregnancy or lactation,
HIV-2 infection (isolated or associated with HIV-1),
History of (experimental) vaccinations against HIV,
Treatment with chemotherapy or interferon alpha (IFN-α-2b), sargramostim (GM-CSF), IL-2 or IL-7 ongoing or in the previous12 weeks before inclusion (W0),
Treatment with corticoids or immunosuppressive agents ongoing or in the previous12 weeks before inclusion in the trial (W0),
Administration of a live vaccine within 60 days prior to inclusion in the trial (W0) or any other inactivated vaccine within 14 days before W0 visit
Planned administration, during the follow-up of participants, of a vaccine other than those recommended in France as part of the usual care of patients
History of cancer (except basal cellular skin carcinoma),
History of cardiovascular disease (angina, myocardial infarction, transient ischemic attack, stroke),
History of renal failure related to HIV,
History of thrombocytopenia related to HIV (<50,000/mm3),
Ongoing cardiac, pulmonary, thyroid, renal or neurological (peripheral or central) diseases,
Progressive infection,
Co-infection with hepatitis B (HBsAg + or isolated anti-HBc antibodies +) or hepatitis C (anti-HCV antibody and PCR +),
Known allergy to aminoglycosides,
Person placed under juridical protection (article L1122-2 of Code de la Santé Publique)
Person participating in another biomedical research with an exclusion period always ongoing at screening.