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Time to ART Resumption following Treatment Interruption Is Shorter for Individuals Immunized with HIV-Recombinant Canarypox Vaccine (Vcp1452) Compared to Placebo: The Manon-02 Trial
Brigitte Autran*1, D Costagliola2, R Murphy3, N Wincker4, B Clotet5, J Gatell6, R Tubiana7, S Staszewski8, B Walker9, C Katlama7, and ORVACS Study Group
1Hosp Pitie Salpetriere, INSERM U543, ORVACS, Univ Pierre et Marie Curie, Paris VI, France; 2INSERM U720, Univ Pierre et Marie Curie Paris VI, France; 3Northwestern University Medical School, Chicago, USA; 4ORVACS, Hôpital Pitié Salpêtrière, Paris, France; 5Fndn irsiCaixa, Hosp Univ Germans Trias i Pujol, Badalona, Spain; 6Hosp y Clin Provincial, Barcelona, Spain; 7Hosp Pitie Salpetriere, ORVACS, INSERM U720, Univ Pierre et Marie Curie, Paris VI, France; 8Klinikum der Johann Wolfgang Goethe Univ, Frankfurt, Germany; and 9Harvard Med Sch, Charlestown, MA, US
Background: We wanted to evaluate whether the immunogenicity of the
HIV-recombinant canarypox vaccine (vCP1452) can be influenced by the number and
schedule of immunizations in ART-treated HIV-infected patients, and to measure
clinical efficacy by determining the time to ART resumption following treatment
interruption post vaccination.
Methods: This was a randomized, international, double-blind,
dose-ranging, placebo-controlled, phase II study in patients with chronic HIV
infection on ART therapy with a median CD4 count of >350 cells/mm3,
a pre-ART CD4 count <400 cells/mm3, and a plasma HIV RNA <400
copies/mL. Patients were randomized to 3 arms: arm A (n = 21) receiving 4 vCP1452 vaccine injections at weeks 0, 4, 8,
and 20; arm B (n = 22): 3 injections at weeks 4, 8, and 20; and arm C
(n = 22) receiving placebo. Patients
were asked to stop ART from week 24 to week 48. Criteria to resume ART included: either, from week
24 to week 48 a CD4 decline <250/mm3 or a CD4 cell count loss
>50% baseline values; or, from week 40 to week 48 a plasma viral load
>50,000 copies/mL. The primary end-point analysis (abstract H-113), showed a significant increase from baseline in
interferon-g (IFN-) -producing T-cell numbers at week 24 post
immunization in the 4-injection arm only, compared to placebo (p = 0.014). Main secondary endpoints
included plasma viral load during treatment interruption and time to resume
ART.
Results: Of the 65 patients enrolled, 54 stopped ART at week 24.
Patients’ characteristics were similar for median pre-ART CD4 nadir of 257
cells/mm3 (IQR 194 to 301) and baseline CD4 counts of 624 cells /mm3
(IQR 553 to 741). Overall, the mean viral load during treatment interruption
was higher in Arm A (4.88, p=0.023), but not in arm B (4.69, p=0.096), compared
to placebo (4.40). A total of 14, 10 and 3 patients reached criteria to resume
ART in arms A (9 for viral load), B (7 for viral load), and C (0 for viral
load). By Kaplan-Meier analysis, the percentage of patients reaching resumption
criteria at week 48 were estimated as 74%, 55%, and 23% in the 3 arms,
respectively (p = 0.013). By
multivariate Cox model, the independent factors influencing time to ART
resumption independently were the 4-injection arm (HR 10.1, 95%CI 2.3 to 44.1)
and the 3-injection arm (HR 6.7, 1.4 to 30.9) compared to placebo, and log2
CD4 nadir (HR 0.3, 0.1 to 0.6).
Conclusions: The significant immunogenicity of the HIV-recombinant
canarypox vaccine in fully suppressed ART-treated, chronically infected
patients is associated with an increased virus production during the
post-immunization treatment interruption and therefore to a shortened delay to
ART resumption.
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