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Randomized Controlled Trial

Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine

Scott M Hammer et al. N Engl J Med. .

Abstract

Background: A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States.

Methods: At 21 sites, we randomly assigned 2504 men or transgender women who have sex with men to receive the DNA/rAd5 vaccine (1253 participants) or placebo (1251 participants). We assessed HIV-1 acquisition from week 28 through month 24 (termed week 28+ infection), viral-load set point (mean plasma HIV-1 RNA level 10 to 20 weeks after diagnosis), and safety. The 6-plasmid DNA vaccine (expressing clade B Gag, Pol, and Nef and Env proteins from clades A, B, and C) was administered at weeks 0, 4, and 8. The rAd5 vector boost (expressing clade B Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C) was administered at week 24.

Results: In April 2013, the data and safety monitoring board recommended halting vaccinations for lack of efficacy. The primary analysis showed that week 28+ infection had been diagnosed in 27 participants in the vaccine group and 21 in the placebo group (vaccine efficacy, -25.0%; 95% confidence interval, -121.2 to 29.3; P=0.44), with mean viral-load set points of 4.46 and 4.47 HIV-1 RNA log10 copies per milliliter, respectively. Analysis of all infections during the study period (41 in the vaccine group and 31 in the placebo group) also showed lack of vaccine efficacy (P=0.28). The vaccine regimen had an acceptable side-effect profile.

Conclusions: The DNA/rAd5 vaccine regimen did not reduce either the rate of HIV-1 acquisition or the viral-load set point in the population studied. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00865566.).

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Figures

Figure 1
Figure 1. Enrollment and Outcomes
Participants could have more than one reason for ineligibility; only the four most common reasons are listed. Partic-ipants who were not included in the per-protocol cohort for multiple reasons are listed in the category in which thefirst protocol violation was reported.
Figure 2
Figure 2. Cumulative Incidence of HIV-1 Infection in Two Population Subgroups
Shown are the cumulative incidences of HIV-1 infection diagnosed from week 28 through month 24 (week 28+ infection) (Panel A) and HIV-1 infec-tion in the modified intention-to-treat population (Panel B). Insets showthe same data on an expanded y axis.
Figure 3
Figure 3. Viral-Load Set Points
Shown are viral-load set points (the mean plasma HIV-1 RNA level 10 to 20 weeks after diagnosis) among partici-pants with HIV-1 infection diagnosed from week 28 through month 24 (week 28+ infection) (Panel A) and HIV-1 in-fection in the modified intention-to-treat population (Panel B). The size of each data point reflects the number ofmeasurements used to compute the mean viral-load set point, which is indicated by the horizontal blue line, with amedian of 4 measurements (range, 1 to 5). The dashed line indicates the lower limit of quantification (LLOQ) of theviral-load assay (40 copies per milliliter). The I bars indicate 95% confidence intervals.

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References

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