[HTML][HTML] Immunotherapy with canarypox vaccine and interleukin-2 for HIV-1 infection: termination of a randomized trial
KA Smith, S Andjelic, Z Popmihajlov… - PLoS Clinical …, 2007 - journals.plos.org
KA Smith, S Andjelic, Z Popmihajlov, L Kelly-Rossini, A Sass, M Lesser, S Benkert, C Waters…
PLoS Clinical Trials, 2007•journals.plos.orgObjectives To determine whether immunotherapy of chronic HIV-1 infection can prevent or
attenuate viremia upon antiviral discontinuation. Design This was a Phase II randomized,
partially double blinded, 2× 2 factorial study of three steps of 12 wk/step. Step I involved four
groups:(1) vaccine placebo,(2) vaccine (ALVAC, vCP1452),(3) placebo+ interleukin 2 (IL-2),
and (4) vaccine+ IL-2. Step II involved a 12-wk diagnostic treatment interruption (DTI). Step
III involved an extension of the DTI for an additional 12 wk. Setting The Weill-Cornell …
attenuate viremia upon antiviral discontinuation. Design This was a Phase II randomized,
partially double blinded, 2× 2 factorial study of three steps of 12 wk/step. Step I involved four
groups:(1) vaccine placebo,(2) vaccine (ALVAC, vCP1452),(3) placebo+ interleukin 2 (IL-2),
and (4) vaccine+ IL-2. Step II involved a 12-wk diagnostic treatment interruption (DTI). Step
III involved an extension of the DTI for an additional 12 wk. Setting The Weill-Cornell …
Objectives
To determine whether immunotherapy of chronic HIV-1 infection can prevent or attenuate viremia upon antiviral discontinuation.
Design
This was a Phase II randomized, partially double blinded, 2×2 factorial study of three steps of 12 wk/step. Step I involved four groups: (1) vaccine placebo, (2) vaccine (ALVAC, vCP1452), (3) placebo + interleukin 2 (IL-2), and (4) vaccine + IL-2. Step II involved a 12-wk diagnostic treatment interruption (DTI). Step III involved an extension of the DTI for an additional 12 wk.
Setting
The Weill-Cornell General Clinical Research Center.
Participants
Chronically infected HIV-1 positive adults with undetectable HIV-1 levels and > 400 CD4+ T cells/μl.
Interventions
An HIV canarypox vaccine (vCP1452) and vaccine placebo, administered every 4 wk for four doses, and low-dose IL-2 administered daily for 12–24 wk.
Outcome measures
Primary endpoints: (1) Proportion of participants with undetectable plasma HIV RNA during trial Step II, (2) mean log10 HIV RNA copies/ml ([HIV]) from weeks 21–25, and (3) proportion of individuals eligible for trial Step III.
Results
44 participants were randomized, but 16 withdrew or were withdrawn before completing Step II. As all participants underwent viral relapse in Step II, the study was terminated after 28 participants completed Step II. Among the four groups, there was no difference in mean [HIV] or the proportion of individuals with < log10 4.48 HIV; no difference between the mean [HIV] of the two groups that received ALVAC (n = 17) versus placebo (n = 11); and no significant difference between the mean [HIV] of the two groups that received IL-2 (n = 11) versus placebo (n = 17).
Conclusions
Neither ALVAC (vCP1452) nor low-dose daily IL-2 nor their combination prevented the relapse of viremia upon discontinuation of antiviral therapy.
Trial Registration
ClinicalTrials.gov NCT00056797
PLOS