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

Scott M. Hammer, Magdalena E. Sobieszczyk, Holly Janes, Shelly T. Karuna, Mark J. Mulligan, Doug Grove, Beryl A. Koblin, Susan P. Buchbinder, Michael C. Keefer, Georgia D. Tomaras, Nicole Frahm, John Hural, Chuka Anude, Barney S. Graham, Mary E. Enama, Elizabeth Adams, Edwin DeJesus, Richard M. Novak, Ian Frank, Carter BentleyShelly Ramirez, Rong Fu, Richard A. Koup, John R. Mascola, Gary J. Nabel, David C. Montefiori, James Kublin, M. Juliana McElrath, Lawrence Corey, Peter B. Gilbert

Research output: Contribution to journalArticle

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.)

Original languageEnglish (US)
Pages (from-to)2083-2092
Number of pages10
JournalNew England Journal of Medicine
Volume369
Issue number22
DOIs
StatePublished - 2013
Externally publishedYes

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HIV-1
Vaccines
DNA
gag-pol Fusion Proteins
Viral Load
env Gene Products
Placebos
Virus Diseases
National Institute of Allergy and Infectious Diseases (U.S.)
Clinical Trials Data Monitoring Committees
nef Gene Products
Infection
Transgender Persons
RNA
DNA Vaccines
Recombinant DNA
Adenoviridae
Vaccination
Plasmids
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hammer, S. M., Sobieszczyk, M. E., Janes, H., Karuna, S. T., Mulligan, M. J., Grove, D., ... Gilbert, P. B. (2013). Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. New England Journal of Medicine, 369(22), 2083-2092. https://doi.org/10.1056/NEJMoa1310566

Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. / Hammer, Scott M.; Sobieszczyk, Magdalena E.; Janes, Holly; Karuna, Shelly T.; Mulligan, Mark J.; Grove, Doug; Koblin, Beryl A.; Buchbinder, Susan P.; Keefer, Michael C.; Tomaras, Georgia D.; Frahm, Nicole; Hural, John; Anude, Chuka; Graham, Barney S.; Enama, Mary E.; Adams, Elizabeth; DeJesus, Edwin; Novak, Richard M.; Frank, Ian; Bentley, Carter; Ramirez, Shelly; Fu, Rong; Koup, Richard A.; Mascola, John R.; Nabel, Gary J.; Montefiori, David C.; Kublin, James; Juliana McElrath, M.; Corey, Lawrence; Gilbert, Peter B.

In: New England Journal of Medicine, Vol. 369, No. 22, 2013, p. 2083-2092.

Research output: Contribution to journalArticle

Hammer, SM, Sobieszczyk, ME, Janes, H, Karuna, ST, Mulligan, MJ, Grove, D, Koblin, BA, Buchbinder, SP, Keefer, MC, Tomaras, GD, Frahm, N, Hural, J, Anude, C, Graham, BS, Enama, ME, Adams, E, DeJesus, E, Novak, RM, Frank, I, Bentley, C, Ramirez, S, Fu, R, Koup, RA, Mascola, JR, Nabel, GJ, Montefiori, DC, Kublin, J, Juliana McElrath, M, Corey, L & Gilbert, PB 2013, 'Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine', New England Journal of Medicine, vol. 369, no. 22, pp. 2083-2092. https://doi.org/10.1056/NEJMoa1310566
Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. New England Journal of Medicine. 2013;369(22):2083-2092. https://doi.org/10.1056/NEJMoa1310566
Hammer, Scott M. ; Sobieszczyk, Magdalena E. ; Janes, Holly ; Karuna, Shelly T. ; Mulligan, Mark J. ; Grove, Doug ; Koblin, Beryl A. ; Buchbinder, Susan P. ; Keefer, Michael C. ; Tomaras, Georgia D. ; Frahm, Nicole ; Hural, John ; Anude, Chuka ; Graham, Barney S. ; Enama, Mary E. ; Adams, Elizabeth ; DeJesus, Edwin ; Novak, Richard M. ; Frank, Ian ; Bentley, Carter ; Ramirez, Shelly ; Fu, Rong ; Koup, Richard A. ; Mascola, John R. ; Nabel, Gary J. ; Montefiori, David C. ; Kublin, James ; Juliana McElrath, M. ; Corey, Lawrence ; Gilbert, Peter B. / Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. In: New England Journal of Medicine. 2013 ; Vol. 369, No. 22. pp. 2083-2092.
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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.)",
author = "Hammer, {Scott M.} and Sobieszczyk, {Magdalena E.} and Holly Janes and Karuna, {Shelly T.} and Mulligan, {Mark J.} and Doug Grove and Koblin, {Beryl A.} and Buchbinder, {Susan P.} and Keefer, {Michael C.} and Tomaras, {Georgia D.} and Nicole Frahm and John Hural and Chuka Anude and Graham, {Barney S.} and Enama, {Mary E.} and Elizabeth Adams and Edwin DeJesus and Novak, {Richard M.} and Ian Frank and Carter Bentley and Shelly Ramirez and Rong Fu and Koup, {Richard A.} and Mascola, {John R.} and Nabel, {Gary J.} and Montefiori, {David C.} and James Kublin and {Juliana McElrath}, M. and Lawrence Corey and Gilbert, {Peter B.}",
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T1 - Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine

AU - Hammer, Scott M.

AU - Sobieszczyk, Magdalena E.

AU - Janes, Holly

AU - Karuna, Shelly T.

AU - Mulligan, Mark J.

AU - Grove, Doug

AU - Koblin, Beryl A.

AU - Buchbinder, Susan P.

AU - Keefer, Michael C.

AU - Tomaras, Georgia D.

AU - Frahm, Nicole

AU - Hural, John

AU - Anude, Chuka

AU - Graham, Barney S.

AU - Enama, Mary E.

AU - Adams, Elizabeth

AU - DeJesus, Edwin

AU - Novak, Richard M.

AU - Frank, Ian

AU - Bentley, Carter

AU - Ramirez, Shelly

AU - Fu, Rong

AU - Koup, Richard A.

AU - Mascola, John R.

AU - Nabel, Gary J.

AU - Montefiori, David C.

AU - Kublin, James

AU - Juliana McElrath, M.

AU - Corey, Lawrence

AU - Gilbert, Peter B.

PY - 2013

Y1 - 2013

N2 - 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.)

AB - 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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