Giuseppe
Emeritus
[Source: The New England Journal of Medicine, full page: (LINK). Abstract, edited.]
Original Article
Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine
Scott M. Hammer, M.D., Magdalena E. Sobieszczyk, M.D., M.P.H., Holly Janes, Ph.D., Shelly T. Karuna, M.D., Mark J. Mulligan, M.D., Doug Grove, M.S., Beryl A. Koblin, Ph.D., Susan P. Buchbinder, M.D., Michael C. Keefer, M.D., Georgia D. Tomaras, Ph.D., Nicole Frahm, Ph.D., John Hural, Ph.D., Chuka Anude, M.D., Ph.D., Barney S. Graham, M.D., Ph.D., Mary E. Enama, M.A., P.A.-C., Elizabeth Adams, M.D., Edwin DeJesus, M.D., Richard M. Novak, M.D., Ian Frank, M.D., Carter Bentley, Ph.D., Shelly Ramirez, M.A., Rong Fu, M.S., Richard A. Koup, M.D., John R. Mascola, M.D., Gary J. Nabel, M.D., Ph.D., David C. Montefiori, Ph.D., James Kublin, M.D., M.P.H., M. Juliana McElrath, M.D., Ph.D., Lawrence Corey, M.D., and Peter B. Gilbert, Ph.D. for the HVTN 505 Study Team
N Engl J Med 2013; 369:2083-2092 / November 28, 2013 / DOI: 10.1056/NEJMoa1310566
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 log<SUB>10</SUB> 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.)
________
Supported by grants from the National Institute of Allergy and Infectious Diseases of the NIH (UM1AI68614, UM1AI068618, UM1AI68635, UM1AI069496, UM1AI69452, UM1AI069412, UM1AI069470, UM1AI069481, UM1AI069439, UM1AI069534, UM1AI069511, UM1AI069554, UM1AI069418, UM1Al069532, UM1AI069424, UM1AI069501, and UM1AI036219 and contract HHSN272200800014C), Columbia University's Clinical and Translational Science Award from the National Center for Advancing Translational Sciences, NIH (UL1TR000040), the NIH Intramural Research Program, Emory Center for AIDS Research (P30AI50409), the Harvard Center for AIDS Research (P30AI06354), the Baylor?University of Texas Houston Center for AIDS Research (UM1AI036211), the Colorado Clinical Translational Science Institute (TR000154), and the National Center for Advancing Translational Science, NIH (UL1TR000451).
The views expressed in this article are those of the authors and do not necessarily represent the official views of the National Institutes of Health (NIH).
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article was published on October 7, 2013, at NEJM.org.
Source Information
The authors' affiliations are listed in the Appendix.
Address reprint requests to Dr. Hammer at the Division of Infectious Diseases, Columbia University Medical Center, 630 W. 168th St., New York, NY 10032, or at smh48@cumc.columbia.edu.
Additional members of the HIV Vaccine Trials Network (HVTN) 505 study team are listed in the Supplementary Appendix, available at NEJM.org.
Appendix
The authors' affiliations are as follows: the Department of Medicine, Columbia University (S.M.H., M.E.S.), and the New York Blood Center (B.A.K.) ? both in New York; Statistical Center for HIV/AIDS Research and Prevention (H.J., D.G., S.R., P.B.G.), Vaccine and Infectious Disease Division (S.T.K., N.F., J.H., C.B., J.K., M.J. McElrath, L.C.), and Program in Biostatistics and Biomathematics (R.F.), Fred Hutchinson Cancer Research Center, Seattle; the Department of Medicine, Emory University, Atlanta (M.J. Mulligan); San Francisco Department of Public Health, San Francisco (S.P.B.); University of Rochester School of Medicine, Rochester, NY (M.C.K.); Duke University, Durham, NC (G.D.T., D.C.M.); the Division of AIDS (DAIDS) (E.A.), Henry M. Jackson Foundation (HJF-DAIDS) (C.A.), and Vaccine Research Center (B.S.G., M.E.E., R.A.K., J.R.M.), National Institute of Allergy and Infectious Diseases, Bethesda, MD; Orlando Immunology Center, Orlando, FL (E.D.); University of Illinois at Chicago, Chicago (R.M.N.); the Department of Medicine, University of Pennsylvania, Philadelphia (I.F.); and Sanofi, Cambridge, MA (G.J.N.).
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Original Article
Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine
Scott M. Hammer, M.D., Magdalena E. Sobieszczyk, M.D., M.P.H., Holly Janes, Ph.D., Shelly T. Karuna, M.D., Mark J. Mulligan, M.D., Doug Grove, M.S., Beryl A. Koblin, Ph.D., Susan P. Buchbinder, M.D., Michael C. Keefer, M.D., Georgia D. Tomaras, Ph.D., Nicole Frahm, Ph.D., John Hural, Ph.D., Chuka Anude, M.D., Ph.D., Barney S. Graham, M.D., Ph.D., Mary E. Enama, M.A., P.A.-C., Elizabeth Adams, M.D., Edwin DeJesus, M.D., Richard M. Novak, M.D., Ian Frank, M.D., Carter Bentley, Ph.D., Shelly Ramirez, M.A., Rong Fu, M.S., Richard A. Koup, M.D., John R. Mascola, M.D., Gary J. Nabel, M.D., Ph.D., David C. Montefiori, Ph.D., James Kublin, M.D., M.P.H., M. Juliana McElrath, M.D., Ph.D., Lawrence Corey, M.D., and Peter B. Gilbert, Ph.D. for the HVTN 505 Study Team
N Engl J Med 2013; 369:2083-2092 / November 28, 2013 / DOI: 10.1056/NEJMoa1310566
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 log<SUB>10</SUB> 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.)
________
Supported by grants from the National Institute of Allergy and Infectious Diseases of the NIH (UM1AI68614, UM1AI068618, UM1AI68635, UM1AI069496, UM1AI69452, UM1AI069412, UM1AI069470, UM1AI069481, UM1AI069439, UM1AI069534, UM1AI069511, UM1AI069554, UM1AI069418, UM1Al069532, UM1AI069424, UM1AI069501, and UM1AI036219 and contract HHSN272200800014C), Columbia University's Clinical and Translational Science Award from the National Center for Advancing Translational Sciences, NIH (UL1TR000040), the NIH Intramural Research Program, Emory Center for AIDS Research (P30AI50409), the Harvard Center for AIDS Research (P30AI06354), the Baylor?University of Texas Houston Center for AIDS Research (UM1AI036211), the Colorado Clinical Translational Science Institute (TR000154), and the National Center for Advancing Translational Science, NIH (UL1TR000451).
The views expressed in this article are those of the authors and do not necessarily represent the official views of the National Institutes of Health (NIH).
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article was published on October 7, 2013, at NEJM.org.
Source Information
The authors' affiliations are listed in the Appendix.
Address reprint requests to Dr. Hammer at the Division of Infectious Diseases, Columbia University Medical Center, 630 W. 168th St., New York, NY 10032, or at smh48@cumc.columbia.edu.
Additional members of the HIV Vaccine Trials Network (HVTN) 505 study team are listed in the Supplementary Appendix, available at NEJM.org.
Appendix
The authors' affiliations are as follows: the Department of Medicine, Columbia University (S.M.H., M.E.S.), and the New York Blood Center (B.A.K.) ? both in New York; Statistical Center for HIV/AIDS Research and Prevention (H.J., D.G., S.R., P.B.G.), Vaccine and Infectious Disease Division (S.T.K., N.F., J.H., C.B., J.K., M.J. McElrath, L.C.), and Program in Biostatistics and Biomathematics (R.F.), Fred Hutchinson Cancer Research Center, Seattle; the Department of Medicine, Emory University, Atlanta (M.J. Mulligan); San Francisco Department of Public Health, San Francisco (S.P.B.); University of Rochester School of Medicine, Rochester, NY (M.C.K.); Duke University, Durham, NC (G.D.T., D.C.M.); the Division of AIDS (DAIDS) (E.A.), Henry M. Jackson Foundation (HJF-DAIDS) (C.A.), and Vaccine Research Center (B.S.G., M.E.E., R.A.K., J.R.M.), National Institute of Allergy and Infectious Diseases, Bethesda, MD; Orlando Immunology Center, Orlando, FL (E.D.); University of Illinois at Chicago, Chicago (R.M.N.); the Department of Medicine, University of Pennsylvania, Philadelphia (I.F.); and Sanofi, Cambridge, MA (G.J.N.).
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