Objective: Evaluate immunogenicity and clinical efficacy of two immunization strategies with the ALVAC-HIV-recombinant canarypox vaccine (vCP1452) in treated HIV-infected patients.
Design: Randomized, double-blind, placebo-controlled, phase II study of vCP1452 immunization in chronically HIV-infected patients on therapy with CD4 T-cell count more than 350 cells/μl, CD4 nadir less than 400 cells/μl and pHIV-RNA less than 400 copies/ml. Patients were equally randomized to four injections at weeks 0, 4, 8, 20; three injections at weeks 4, 8, 20; and placebo. The primary endpoint was vaccine immunogenicity at week 24 measured by enzyme-linked immunospot-interferon-γ against the HIV-gag-reverse transcriptase-nef vaccine sequences. Secondary endpoints included time to treatment resumption and viral quantitation following treatment interruption at week 24. Criteria to resume therapy included CD4 T-cell count decline less than 250 cells/μl or 50% decrease from baseline or pHIV-RNA more than 50 000 copies/ml.
Results: Sixty-five patients enrolled. Changes from baseline in HIV-specific T cells in the four injection arms (+480 spot-forming cells/M-peripheral blood mononuclear cell) were significant compared to placebo (+8; P = 0.014), but not in the three injection arms (+322). The week 36 pHIV-RNA (log10 copies/ml) after treatment interruption was higher in the four (4.71; P = 0.023) and three (4.82; P = 0.009) injection arms compared to placebo (4.40). Percentages of patients reaching treatment resumption criteria by week 48 were 74, 55 and 23% in the three respective arms (P = 0.013). Two independent factors influenced time to therapy resumption: immunization (hazards ratio = 2.7, P = 0.048 for three injections; hazards ratio = 4.1, P = 0.003 for four injections) and CD4 nadir (hazards ratio = 0.4, P = 0.002).
Conclusions: Significant immunogenicity was induced by vCP1452; however, this strategy was independently associated with a shorter time to resume therapy and higher viral rebound.
From the aUPMC Univ Paris 06, UMR_543, France
bAP-HP, Pitié-Salpétrière Hospital, France
cINSERM, UMR_ 543, Cellular Immunology Laboratory, France
dAP-HP, Infectious and Tropical Diseases Department, Pitié-Salpétrière Hospital, France
eUPMC Univ Paris 06, UMR_720, Clinical and Therapeutic Epidémiology of HIV Infection, Paris, France
fNorthwestern University, Chicago, Illinois, USA
gINSERM, UMR_720, Clinical and Therapeutic Epidémiology of HIV Infection, Paris, France
hIrsi Caixa, Foundation, Spain
iInfectious Diseases Department, Hospital y Clinic Provincial, Barcelona, Spain
jJ. W. Goethe-University, Frankfurt, Germany
kORVACS, F-75013, Paris
lSanofi-Pasteur, Marcy l'Etoile, France
mAP-HP, Virology Laboratory, Pitié-Salpétrière Hospital, France
nUPMC Univ Paris 06,Paris, France
oPartners AIDS Research Center, General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachussets, USA.
Received 19 November, 2007
Revised 18 February, 2008
Accepted 19 February, 2008
Correspondence to Professor Brigitte Autran, Laboratoire d'Immunologie Cellulaire et Tissulaire, Hôpital Pitié Salpétrière, 83 Blvd de l'Hôpital, 75013 Paris, France. E-mail: email@example.com