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.
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 log(10) HIV-1 RNA load at the ATI set point and the time-averaged area under the curve served as co-primary 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 P < or = 25. The estimated 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) log(10) copies lower, respectively, in the vaccine arm than in the placebo arm. HIV-1 gag-specific CD4(+) cells producing interferon-gamma were an immunologic correlate of viral control.


CONCLUSIONS
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.
Schooley
Robert T
RT
Div. of Infectious Diseases,University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. arsexton@ucsd.edu
Spritzler
John
J
Wang
Hongying
H
Lederman
Michael M
MM
Havlir
Diane
D
Kuritzkes
Daniel R
DR
Pollard
Richard
R
Battaglia
Cathy
C
Robertson
Michael
M
Mehrotra
Devan
D
Casimiro
Danilo
D
Cox
Kara
K
Schock
Barbara
B
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D014779:Virus Replication
D016915:AIDS Vaccines; D015683:Gene Products, gag; D019444:Vaccines, DNA; D007371:Interferon-gamma