AEGiS-14IAC: 3-year evaluation of a therapeutic vaccine (HIV-1 Immunogen) administred with antiretrovirals versus antiretroviral therapy alone in patients with HIV chronic infection.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

3-year evaluation of a therapeutic vaccine (HIV-1 Immunogen) administred with antiretrovirals versus antiretroviral therapy alone in patients with HIV chronic infection.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1482)

Fernandez-Cruz E, Navarro J, Abad ML, Diaz L, Canto-Nogues C, Rodriguez-Sainz MC, Carbone J, Munoz-Fernandez MA, Moreno S, Perez-Molina J, Clotet B, Gatell JM, Podzamczer D, Gonzalez-Lahoz J
Hospital General Univ Gregorio Maranon, Madrid, Spain

BACKGROUND: We evaluated the efficacy of therapeutic vaccine with an inactivated gp120-depleted HIV-1 immunogen in IFA (REMUNETM) in 243 HIV+ chronically infected subjects while receiving either ART or HAART (ARTs) in a three year, double-blind, placebo (IFA) controlled trial. We determined the impact on viral rebound or CD4 cell decline.

RESULTS: REMUNE impacted significantly on virologic failure in patients on ARTs (Fisher's Exact test, p<0.05). Also, there was a significant delay in the time to reach virologic failure that was impacted by baseline viral load and CD4 in-patients on ARTs (Cox Regression Model, p<0.05). REMUNE also improved the maintenance of virologic suppression in patients on ARTs (Gompertz model, p<0.001). In a pre-specified subgroup of 54 subjects a significant lymphoproliferative response (LPR) was also observed in REMUNE-patients as compared with IFA group. (stimulation index=29.6 vs 5.8, p<0.005). An increase of CD8 memory T cells (CD8+CD45RO+) was observed in REMUNE-Group (n=27) vs IFA-Group (n=27) (p<0.05). Also, high levels of HIV-1 Gag/pol-specific CTL precursors were observed in REMUNE group vs IFA-Group (mean: 3.224 CTLp vs 169 CTLp/106 PBMC; P<0.05). CTL precursors correlated negatively with viral load in the REMUNE group (R= -0.58; P<0.05) but not in the IFA group. LPR correlated positively with CTL precursors (R=0.498, p<0.05) and with Lytic Units (R=0.686, p<0.005). We found a positive correlation between CD38+DR+ (R=0.60, p<0.05) and CD45RO+DR+ (R=0.44, p<0.05) CD4+ T cells with viral load in IFA-Group, but not in REMUNE-Group. Increased CD11b+ (p<0.05) and decreased HLADR+ (p<0.005) CD8+- T-cells was only found in REMUNE-treated patients who developed high HIV-specific CTLs.

CONCLUSIONS: Therapeutic vaccination induces a decrease of immune system activation, an increase of HIV-specific helper and CTL immune responses, and induces a positive impact on the control of viral load in immunocompetent HIV-1 infected patients on ARTs.

Keywords: AEGIS, HIV-1, HIV Infections, AIDS Vaccines, Viral Load, HIV Seropositivity, CD4-Positive T-Lymphocytes, Antigens, CD4, remune, Human, therapy, immunology

020707
ThOrA1482