HIV Infection
Conditions
Keywords
HIV-1 infection, therapeutic vaccine, Treatment Experienced
Brief summary
Prior pilot studies have shown that four monthly injections of ALVAC-HIV (vCP1433) are immunogenic in 60% HIV-infected patients with a boosting effect obtained after 1 or 2 injections followed by a plateau or a decrease of these responses prior to interrupting therapy. The goal of the present study is to look for an improved vaccination schedule in terms of strength and duration of the HIV-specific immunity induced by the HIV-recombinant canary pox vector ALVAC-HIV (vCP1452) by testing a strategy of immunization involving a first series of two versus three monthly injections followed by a boost three months later.
Detailed description
Manon 02 is a phase II, multicentre, randomized, placebo-controlled study with 3 arms comprising 2 steps: Step I : Immunization phase from W0 to W24, on HAART The immunization will be administered by intramuscular injection : Arm A: one injection of vCP1452 at W0, W4, W8 and W20 + HAART, for a total of 4 injections Arm B: one injection of vCP1452 at W4, W8 and W20 + HAART, for a total of 3 injections Arm C: one injection of placebo at W0, W4, W8 and W20 + HAART, for a total of 4 injections or at W4, W8 and W20 + HAART, for a total of 3 injections Step II: Post immunization phase from W24 to W48, off HAART Discontinuation of antiretroviral therapy (ARV) from W24 to W48 : The ARV treatment interruption will be proposed at W24, 4 weeks after the last immunization, to patient who had completed their immunization phase and have CD4 cell counts \> 350 cells/mm3 and HIV plasma RNA \< 400 cp/ml. In order to be able to evaluate the capacity of the immune response to reduce the viral replication, a period of 16 weeks of interruption is recommended from W24 to W40. Resumption of antiretroviral therapy : From W24 to W40 : During this 16 weeks period, in case of a decline of CD4 cell counts below 250 cells/mm3 or of a loss of CD4 greater than 50% of the baseline value, HAART will be restarted. From W40 to W48 : HAART should be reintroduced if HIV-1 RNA levels \> 50 000 cp/ml on 2 consecutive measurements at two weeks interval even if the CD4 counts are above 250 cells/mm3.
Interventions
BIOLOGICALone injection of vCP1452 at W0, W4, W8 and W20
BIOLOGICALone injection of vCP1452 at W4, W8 and W20
BIOLOGICALone injection of placebo at W0, W4, W8, W20 or at W4, W8,W20
Sponsors
Objectif Recherche Vaccins SIDA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented HIV infection * under potent antiretroviral therapy for more than 6 months * with entry CD4+ counts \> 350 cells/mm3 for at least 1 year * plasma HIV RNA \< 400 cp/ml for at least the last 6 months * Contraception needed for women
Exclusion criteria
* Antiretroviral therapy started with CD4 cell count \> 400/mm3 * Patients treated at time of primary HIV infection * Patient with past AIDS defining event
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline of the frequency of HIV-specific PBMC (CD4/CD8) at W24 (4 weeks after the last immunization) | — |
Secondary
| Measure | Time frame |
|---|---|
| - Change from baseline of the frequency of HIV-specific PBMC and/or CD4 and/or CD8 T cells at week 4, 6, 8, 12, 20 and 24 in the study arms as measured by ELISpot IFNγ | — |
| - Evaluation of the magnitude of CD4 and CD8 T cell response at W4, W6, W8, W12, W20, W24 in the study arms | — |
| - Evaluation of the immune responses, HIV-specific PBMC and/or CD4 and/or CD8 T cells at W48 | — |
| - Percentage of patients who generate a primary immune response against the artificial pol/nef sequences present in the vaccine but not in the HIV strain | — |
| - Percentage of responders as defined by an increase of at least 0.7 log10 from baseline of the frequencies of HIV-specific PBMC and/or CD4 and/or CD8 T cells four weeks after the last immunization(W24) as measured by ELISpot IFNγ | — |
| - Percentage of patients who do not reach the restart therapy criteria from W24 to W48 | — |
| - Percentage of patients who remain off therapy at W48 | — |
| - Evaluation of the safety and tolerability of the vCP1452 | — |
| - Evaluation of the immune responses directed to vCP1452 in the study arms at all study point during the immunization phase | — |
Countries
France, Germany, Spain, United States
Outcome results
None listed