Session 14Oral Abstract Presentations Immune-Based Therapy Session Day and Time: Wednesday 10 - 11:15 am Presentation Time: 10:30 Room: Auditorium
61 Therapeutic Vaccination with ALVAC-HIV vCP1433: A Recombinant Canarypox Vaccine in Chronically HIV-1 Infected Patients Treated with HAART: VACCITER (ANRS 094) R. Tubiana*1, G. Carcelain1, M. Vray1, K. Gourlain1, S.Hilpert1, C. Dalban1, A. Chermak1, R. El Habib2, M. Klein2, D. Costagliola1, V. Calvez1, B. Autran1, C. Katlama1, Vacciter Study Group3 1Pitié-Salpêtrière Hosp, Paris, France; 2Aventis Pasteur, Lyon, France; and 3Agence Natl de Res sur le SIDA, Paris, France
Background: To evaluate safety, immunogenicity, and ability of ALVAC HIV vCP1433 a recombinant canarypox carrying HIV-1 genes (env, gag, epitopes of pol, nef), to control viral replication in chronically HIV-infected patients (pts).
Methods: In this pilot, open, prospective non comparative study HIV-infected pts (nadir of CD4 > 200 cells/µl) stable under HAART (< 200 HIV-RNA copies/ml, CD4 > 400 cells/µl) for at least 12 months were eligible. While on antiretroviral (ARV) therapy, pts received 4 IM injections (D0, W4, 8, 12) of Vcp1433. At W16 (A0) ARV were interrupted and pts were monitored every 2 wks. Criteria for resuming ARV were: plasma HIV-RNA > 50.000 cp/ml within or > 10.000 cp/ml after 8 wks of interruption or CD4 < 250 cells/µl. End-points included the percentage of pts with a PVL < 10,000 cp/ml after 20 wks of interruption, the delay to ARV re-initiation, the immunogenicity of ALVAC/vCP1433 evaluated by p24 CD4 LPA, and quantification of anti-HIV CD8 T cells by IFNg-ELISpot using pools of peptides of gag in a subset of 19 pts.
Results: Forty-eight (48) pts (median CD4: 747/µl (415-1,597)) started the study. All received the 4 scheduled injections and no significant adverse effects were observed. Twelve (12) out of 48 pts were p24 LPA positive before vaccination. Among the 36 other pts, 22 (61%) developed their first positive response during the immunization. These responses occurred after 1 (n = 10), 2 (n = 3) or 3 (n = 7) injections in 20/22 (91%). In responders the median SI increased from 3.3 (0.3-31.7) at baseline to 13.1 (1.8-63.1) after 2 injections but decrease to 6.8 (1.3-24.9) at A0. Overall 38/48 (79%) pts restarted ARV in a median delay of 6.6 weeks (3.7-44), 10/48 pts (21%) are still in interruption at W44 of follow-up. Median time to restart ARV was higher for p24 LPA positive pts at A0 (n = 10) as compared to those with no response at this time point (n = 36): 9.71 vs 6.3 weeks (p = 0.02, log rank). A > 3-fold expansion of HIV-gag specific CD8+ T-cells was observed in 7/19 (37%) pts during the vaccination phase without correlation with delay to restart ARV.
Conclusions: These preliminary results show that immunization with vCP1433 in chronic infection is safe and able to boost specific immune response. Four (4) repeated vCP injections might over stimulate the immune system of pre-sensitized HIV-infected pts and limit vaccine efficacy. However, viral replication is better controlled in pts with positive p24 LPA at time of interruption.