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 (log 10 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.