Background:  We have determined whether therapeutic immunization with an HIV-1 Immunogen (Remune; REM) during analytical treatment interruption maintain the HIV-1-specific responses in HIV⁺ patients previously sensitized with REM.

Methods:  All participants had taken part in a randomized, double-blind study (STIR-2102) and had received REM on open label for 24 additional months. We randomized 39 patients to receive, every 3 months, either REM (n = 21) or placebo (IFA) (n = 19) in combination with ART for 36 months and to undergo analytical treatment interruption for 48 weeks (REMIT-2102). Specific lymphoproliferative responses were determined by ³H-thymidine incorporation and by CFSE (5,6-carboxyfluorescein diacetate succinimidyl ester) assays, T-cell subsets were evaluated by flow cytometry and ELISpot assays were used to evaluate CD8⁺ HIV-specific responses, every 3 months throughout the study.

Results:  Patients included in REMIT varied with respect to the number of doses of REM received prior to initiation of ATI:  25% = 8 doses; 50% = 12 doses; 75% = 23 doses. Patients who received higher doses of REM (REM^high; n = 19 ) showed increased specific CD4⁺ and CD8⁺ T-cell proliferation during treatment interruption than those at lower doses (REM^low; n = 20) (%CD4⁺CFSE^low: REM^high = 5.5 vs. REM^low = 1; %CD8⁺CFSE^low:  REM = 11.8 vs IFA = 1.9; p = 0.02). Specific lymphoproliferative responses to HIV-1 antigens were higher at week 48 (20,973±4397 copies/mL) in REM^high group compared with REM^low (9252±2536; p = 0.03). There were no significant differences between REM^high and REM^low groups in CD4⁺ and CD8⁺ responses to HIV-1 antigens by ELISpot. However, patients who received REM during treatment interruption showed a significant increase of CD8⁺ Gag-specific interferon-gamma (IFN-γ) -producing cells (p = 0.027). Only patients randomized to REM arm showed a positive association between lymphoproliferative responses (p24 antigen), HIV-1-specific IFN-γ-producing cells (p = 0.017) and terminally differentiated effector CD8⁺ T cells (CD8⁺CD28^–CD57⁺) (p = 0.01). The REM arm had an increase in the percentage of central memory T cells (CD45RA^–CD62L⁺) from week 0 to week 48 (CD4⁺: 34±2 vs 42±2; p = 0.021; and CD8⁺:  10±1 vs 14±1; p = 0.048). By ANOVA Mixed Model analysis the mean adjusted difference between REM and IFA arms was 0.3 log HIV RNA (p <0.001).

Conclusions:  Therapeutic immunization with an HIV-1 Immunogen during analytical treatment interruption results in the expansion of pre-existing HIV-specific immune responses in patients previously sensitized to the Immunogen. The long-term maintenance of immunological responses was associated with a better viral load control.