Session 14Oral Abstract Presentations Immune-Based Therapy Session Day and Time: Wednesday 10 - 11:15 am Presentation Time: 10:45 Room: Auditorium
62 Immunological and Virological Efficacy of ALVAC-VIH 1433 and HIV Lipopeptides (Lipo-6T) Combined with SC IL-2 in Chronically HIV-infected Patients-Results of the ANRS 093 Randomized Study Y Levy*1, H Gahery-Segard2, C Durier3, A-S Lascaux1, V Meiffrédy3, C Goujard4, J-P Cassuto5, C Rouzioux6, R Elhabib7, J-G Guillet8, J-P Aboulker3, J-F Delfraissy4, ANRS 093 Study Group9 1Hosp Henri Mondor, Créteil; 2INSERM, U445, Paris; 3INSERM, SC10, Villejuif; 4Hosp Bicêtre, Kremlin-Bicêtre, France; 5Hosp Archet, Nice, France; 6Hosp Necker, Paris, France; 7Aventis Pasteur, Lyon, France; 8Hosp Cochin, Paris, France; and 9Agence Natl de Res sur le SIDA, Paris, France Paris, France
Background: To evaluate the immunogenicity of the vaccine strategy and its impact on HIV replication after HAART discontinuation.
Methods: Seventy (70) patients (pts) with CD4 > 350 cells/ml and HIV RNA < 50 cp/ml, treated for at least 1 yr with HAART alone (n = 55) or combined with IL-2 (n = 15), were randomized to continue either HAART alone (control, n = 37) or combined with ALVAC and Lipo-6T administered at wk 0, 4, 8 and 12 followed by 3 cycles of IL-2 (4.5 MIU, bid, 5 d) at wk 16, 24, 32 (Vac-IL-2, n = 33). Pts whose plasma HIV RNA was < 50 cp/ml at wk 36 were proposed to stop HAART at wk 40. Intent-to-treat analysis of: 1) proportion of pts with virological failure at wk 52 defined by re-initiation of HAART if viral load > 50,000 at wk 44 or after wk 48 if >10,000 cp/ml; 2) LPR to p24 and 11 peptides from gag, pol, nef, and env, was done.
Results: At wk 40, 63/69 (91%) pts stopped HAART. At wk 52, 2/37 (5%) controls and 8/33 (24%) vaccinated were off HAART (p = 0.027). Time (median, d) to peak of HIV RNA and to virological failure was delayed in Vac-IL-2 arm (41.5 and 42) compared to controls (34 and 29) (p = 0.02 and 0.009, respectively). Prior IL-2 therapy (trend, p = 0.13) and lower proviral DNA at wk 0 (p < 0.001) were associated with HIV control at wk 52, but the comparison between vaccinated pts and controls remains significant after adjustment on these baseline factors (p = 0.032). In Vac-IL-2 arm, number of pts with a sustained p24 LPR at wks 16 and 36 (15/32) and with LPR = 1 peptide (19/33) was significantly higher than controls (8/33 and 9/36) (p = 0.049 and 0.006, respectively). Logistic-regression analysis demonstrated that these 2 parameters were predictive of HIV control at wk 52 (p = 0.046 and 0.014).
Conclusions: Vaccinated pts experienced a better control of HIV replication after stopping HAART. This effect is associated to the stimulation of a sustained and a polyepitopic HIV immune response.
