Background:  The first phase of the randomized trial ANRS 093 demonstrated that therapeutic immunization enhances cellular HIV-specific responses and resulted in the control of viremia following HAART interruption in a higher proportion of patients as compared with non-vaccinated controls. A second phase of the study was scheduled until week 100.

Methods:  HAART treated patients with CD4 > 350 cells/µL, HIV RNA (plasma viral load) < 50 copies/mL, were randomized to HAART alone (n = 37) or combined with ALVAC vCP1433 and HIV-Lipo-6T administered at week 0, 4, 8, 12 followed by 3 cycles of SC IL-2 (4.5 MIU, twice daily for 5 days) at week 16, 24, 32 (n = 33). At week 40, HAART was interrupted and not resumed as long as plasma viral load remained < 50,000 copies/mL 4 weeks later and < 10,000 at subsequent determinations every 4 weeks. The latter criterion defined time off HAART indication. During the second phase of the trial (> week 52), patients who had resumed HAART and exhibited plasma viral load < 50 copies/mL underwent subsequent treatment interruption and follow-up with the same definition of time off HAART indication as in the first phase. Analyses of the total cumulative time off HAART indication, clinical and virological outcomes following treatment interruption, correlations between immunological parameters (LPR to HIV peptides, IFN-g ELISpot responses to 15-mer HIV pools) and time off HAART were performed.

Results:  All patients, but 1, completed the study. In an intent-to-treat analysis, the median cumulative time (days) off treatment indication was greater in the vaccine group (177) than in the control group (89) (p = 0.01). The mean (SE) per-patient time off HAART indication was 42.8% (5.1) and 26.5% (4.2) in the vaccine and control groups, respectively (p = 0.005). At week 100, 38% of vaccinated and 19% of control patients were off HAART indication (p = 0.085). Viremia (median log₁₀ copies/mL), 4 weeks following the first, second, and third treatment interruption, was higher in control patients (4.81, 4.44, 4.53) as compared with vaccinated patients (4.48, 4.00, 3.66) (p = 0.42, 0.015, and 0.024, respectively). During treatment interruption, 5 control patients and no vaccinated patients developed an AIDS-defining event (p = 0.05). HIV-specific LPR at week 16, but not at entry, and therapeutic immunization were strongly correlated with the total time off HAART (p = 0.0027 and 0.016, respectively).

Conclusions:  These results provide evidence that a sustained control of viremia correlated with enhanced viral-specific cellular responses may be achieved through therapeutic immunization in chronic HIV-1 infection. These effects translated into a significant reduction in exposure to HAART.

Keywords: therapeutic vaccine; IL-2