Abstract
Background. Human immunodeficiency virus type 1 (HIV-1)-specific cellular immunity contributes to the control of HIV-1 replication. HIV-1-infected volunteers who were receiving antiretroviral therapy were given a replication-defective adenovirus type 5 HIV-1 gag vaccine in a randomized, blinded therapeutic vaccination study. Methods. HIV-1-infected vaccine or placebo recipients underwent analytical treatment interruption (ATI) for 16 weeks. The log10 HIV-1 RNA load at the ATI set point and the time-averaged area under the curve served as coprimary end points. Immune responses were measured by intracellular cytokine staining and carboxyfluorescein succinimidyl ester dye dilution. Results. Vaccine benefit trends were seen for both primary end points, but they did not reach a prespecified significance level of . The estimated P ≤.025 shifts in the time-averaged area under the curve and the ATI set point were 0.24 (P=.04 , unadjusted) and 0.26 ( P=.07, unadjusted) log10 Pp.04 Pp.07 copies lower, respectively, in the vaccine arm than in the placebo arm. HIV-1 gag-specific CD4+ cells producing interferon-γ were an immunologic correlate of viral control. Conclusion. The vaccine was generally safe and well tolerated. Despite a trend favoring viral suppression among vaccine recipients, differences in HIV-1 RNA levels did not meet the prespecified level of significance. Induction of HIV-1 gag-specific CD4 cells correlated with control of viral replication in vivo. Future immunogenicity studies should require a substantially higher immunogenicity threshold before an ATI is contemplated.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 705-716 |
| Number of pages | 12 |
| Journal | Journal of Infectious Diseases |
| Volume | 202 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 1 2010 |
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ASJC Scopus subject areas
- Infectious Diseases
- Immunology and Allergy
Cite this
AIDS clinical trials group 5197 : A placebo-controlled trial of immunization of HIV-1-infected persons with a replication-deficient adenovirus type 5 vaccine expressing the HIV-1 core protein. / Schooley, Robert T.; Spritzler, John; Wang, Hongying; Lederman, Michael M.; Havlir, Diane; Kuritzkes, Daniel R.; Pollard, Richard B; Battaglia, Cathy; Robertson, Michael; Mehrotra, Devan; Casimiro, Danilo; Cox, Kara; Schock, Barbara.
In: Journal of Infectious Diseases, Vol. 202, No. 5, 01.09.2010, p. 705-716.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - AIDS clinical trials group 5197
T2 - A placebo-controlled trial of immunization of HIV-1-infected persons with a replication-deficient adenovirus type 5 vaccine expressing the HIV-1 core protein
AU - Schooley, Robert T.
AU - Spritzler, John
AU - Wang, Hongying
AU - Lederman, Michael M.
AU - Havlir, Diane
AU - Kuritzkes, Daniel R.
AU - Pollard, Richard B
AU - Battaglia, Cathy
AU - Robertson, Michael
AU - Mehrotra, Devan
AU - Casimiro, Danilo
AU - Cox, Kara
AU - Schock, Barbara
PY - 2010/9/1
Y1 - 2010/9/1
N2 - Background. Human immunodeficiency virus type 1 (HIV-1)-specific cellular immunity contributes to the control of HIV-1 replication. HIV-1-infected volunteers who were receiving antiretroviral therapy were given a replication-defective adenovirus type 5 HIV-1 gag vaccine in a randomized, blinded therapeutic vaccination study. Methods. HIV-1-infected vaccine or placebo recipients underwent analytical treatment interruption (ATI) for 16 weeks. The log10 HIV-1 RNA load at the ATI set point and the time-averaged area under the curve served as coprimary end points. Immune responses were measured by intracellular cytokine staining and carboxyfluorescein succinimidyl ester dye dilution. Results. Vaccine benefit trends were seen for both primary end points, but they did not reach a prespecified significance level of . The estimated P ≤.025 shifts in the time-averaged area under the curve and the ATI set point were 0.24 (P=.04 , unadjusted) and 0.26 ( P=.07, unadjusted) log10 Pp.04 Pp.07 copies lower, respectively, in the vaccine arm than in the placebo arm. HIV-1 gag-specific CD4+ cells producing interferon-γ were an immunologic correlate of viral control. Conclusion. The vaccine was generally safe and well tolerated. Despite a trend favoring viral suppression among vaccine recipients, differences in HIV-1 RNA levels did not meet the prespecified level of significance. Induction of HIV-1 gag-specific CD4 cells correlated with control of viral replication in vivo. Future immunogenicity studies should require a substantially higher immunogenicity threshold before an ATI is contemplated.
AB - Background. Human immunodeficiency virus type 1 (HIV-1)-specific cellular immunity contributes to the control of HIV-1 replication. HIV-1-infected volunteers who were receiving antiretroviral therapy were given a replication-defective adenovirus type 5 HIV-1 gag vaccine in a randomized, blinded therapeutic vaccination study. Methods. HIV-1-infected vaccine or placebo recipients underwent analytical treatment interruption (ATI) for 16 weeks. The log10 HIV-1 RNA load at the ATI set point and the time-averaged area under the curve served as coprimary end points. Immune responses were measured by intracellular cytokine staining and carboxyfluorescein succinimidyl ester dye dilution. Results. Vaccine benefit trends were seen for both primary end points, but they did not reach a prespecified significance level of . The estimated P ≤.025 shifts in the time-averaged area under the curve and the ATI set point were 0.24 (P=.04 , unadjusted) and 0.26 ( P=.07, unadjusted) log10 Pp.04 Pp.07 copies lower, respectively, in the vaccine arm than in the placebo arm. HIV-1 gag-specific CD4+ cells producing interferon-γ were an immunologic correlate of viral control. Conclusion. The vaccine was generally safe and well tolerated. Despite a trend favoring viral suppression among vaccine recipients, differences in HIV-1 RNA levels did not meet the prespecified level of significance. Induction of HIV-1 gag-specific CD4 cells correlated with control of viral replication in vivo. Future immunogenicity studies should require a substantially higher immunogenicity threshold before an ATI is contemplated.
UR - http://www.scopus.com/inward/record.url?scp=77955671541&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955671541&partnerID=8YFLogxK
U2 - 10.1086/655468
DO - 10.1086/655468
M3 - Article
C2 - 20662716
AN - SCOPUS:77955671541
VL - 202
SP - 705
EP - 716
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 5
ER -