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. 2007 Jan 26;2(1):e5.
doi: 10.1371/journal.pctr.0020005.

Immunotherapy with canarypox vaccine and interleukin-2 for HIV-1 infection: termination of a randomized trial

Kendall A Smith  1 , Sofija Andjelic, Zoran Popmihajlov, Liza Kelly-Rossini, Aquanette Sass, Martin Lesser, Steven Benkert, Cory Waters, Joyce Ruitenberg, Paul Bellman
Affiliations

Immunotherapy with canarypox vaccine and interleukin-2 for HIV-1 infection: termination of a randomized trial

Kendall A Smith et al. PLoS Clin Trials. .

Abstract

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, 2x2 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/microl.

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Results: 44 participants were randomized, but 16 withdrew or were withdrawn before completing Step II.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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Participant Flow
Each box represents the flow of participants through the study, from screening to enrollment to randomization and analysis. AE, adverse event necessitating withdrawal from study; WD, individual withdrew from study (see text).
Figure 2
Figure 2. Plasma [HIV] during Steps II and III of Individuals According to Immunotherapy Treatment Group
Red vertical line in center of each figure depicts the demarcation between Step II and Step III. Fractions in upper right corner of each figure portray the number of participants who were eligible to enter Step III in each group.
Figure 3
Figure 3. Results from Interim Analysis
This was a 2×2 factorial study with participants randomized to receive vaccine (+) or not (−), and IL-2 (+) or no-IL-2 (−). The numbers listed in each block are the mean plasma [HIV] log10 RNA copies/ml for each participant from the last 5 weeks of Step II (i.e., weeks 21–25). There was no significant difference between the means of each group based on a 2×2 ANOVA.
Figure 4
Figure 4. Mean CD8+ and CD4+ T cell Concentrations of the Four Immunotherapy Groups during Step II
(A) CD8+ T cells. (B) CD4+ T cells. Blue diamonds = group A, placebo; red squares = group B, vaccine; green triangles = group C, IL-2; black circles = group D, IL-2 + vaccine. Brackets depict SEM.
Figure 5
Figure 5. Mean HIV p55 gag-Specific T Cells Capable of Producing IFN-γ According to Treatment Group
(A) [CD8+ T cell]. (B) [CD4+ T cell]. Brackets depict SEM. Bkg, background.
Figure 6
Figure 6. Mean HIV p55 gag-Specific T Cells Capable of Producing TNF-α According to Treatment Group
(A) [CD8+ T cell]. (B) [CD4+ T cell]. Brackets depict SEM. Bkg, background.
Figure 7
Figure 7. Mean HIV p55 gag-Specific T Cells Capable of Producing IL-2 According to Treatment Group
(A) [CD8+ T cell]. (B) [CD4+ T cell]. Brackets depict SEM. Bkg, background.
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