Immunogenicity and Safety of 2 Schedules of ALVAC-HIV vCP1452 in Chronically HIV-Infected Patients (MANON 02)

• Change from baseline of the frequency of HIV-specific PBMC (CD4/CD8) at W24 (4 weeks after the last immunization)
  

• - 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
  
• - 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
  
• - Evaluation of the immune responses directed to vCP1452 in the study arms at all study point during the immunization phase
  
• - 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
  

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.