Session Day and Time: Wednesday 1:30 - 3:30 pm
Room: Hall A
Background: We have shown previously that an anti-HIV lipopeptide vaccine using large peptides injected to HIV-uninfected volunteers is well tolerated and is able to induce specific CD4+ and CD8+ T-cell responses (ANRS, VAC 04 Trial). The same mixture of HIV-1 lipopeptide vaccine was injected in chronically-infected patients controlled by HAART to evaluate the immunogenicity and its impact on HIV replication after HAART interruption.
Methods: In an open pilot trial, 24 HIV-1 chronically infected patients (pts) treated at least 1 yr with HAART, with undetectable HIV-RNA and a CD4+ T-cell count > 350/mm3 were immunized 3 times with the mixture of the 6 lipopeptides (3 Nef, 2 Gag, and 1 Env) at 0, 3 and 6 wks. At wk 24, pts with HIV-RNA < 50 cp/ml were proposed to stop HAART. We studied CD4+ T-cell proliferative responses. An IFN-g ELISpot method was used to characterize the anti-HIV-1 CD8+ T-cell responses. After HAART interruption viral load was measured. Re-initialization of HAART was decided if viral load was > 30,000 cp/mL 1 month after HAART interruption.
Results : At wk 0, anti-HIV CD4+ and CD8+ T-cell responses to Gag, Nef and Env large peptides were detected in few pts. After immunization only pts with new specific T-cell responses were classified to be responders to the vaccine. After 3 injections 16/24 (67%) pts have induced a specific CD4+ T-cell response to at least 1 peptide and PBMCs from 8 of these pts proliferated to at least 2 of the 6 peptides included in the vaccine. The proliferative response was mainly directed to Gag 253-284. Thus, proliferation to this large peptide was obtained with PBMCs from 10/19 (53%) vaccinated pts and 7 of them have a sustained response. Preliminary data show that CD8+ T-cell responses were induced in 14/20 vaccinated pts. The impact of the vaccine on HIV replication was evaluated in only 17 pts. One (1) yr after HAART interruption 7/17 (41%) vaccinated pts were off HAART and 5 of them have a viral load < 10,000 cp/mL. Six (6) of these 7 pts have induced new CD4+ or CD8+ T-cell responses after vaccination.
Conclusion : Lipopeptides are able to induce new anti-HIV immune responses in HIV-infected pts after vaccination. Some vaccinated pts were able to better control their viral replication after HAART interruption.