M A J O R A R T I C L E
An Ad5-Vectored HIV-1 Vaccine Elicits
Cell-mediated Immunity but does not Affect
Disease Progression in HIV-1–infected Male
Subjects: Results From a Randomized
Placebo-Controlled Trial (The Step Study)
D. W. Fitzgerald,1H. Janes,2M. Robertson,3R. Coombs,4I. Frank,5P. Gilbert,2M. Loufty,6D. Mehrotra,3and A. Duerr,2for
the Step Study Protocol Teama
1Center for Global Health, Weill Cornell Medical College, New York, New York;2Fred Hutchinson Cancer Research Center, Seattle, Washington;3Merck
Research Laboratories, North Wales, Pennsylvania;4Departments of Laboratory Medicine & Medicine, University of Washington, Seattle;
5Department of Medicine, University of Pennsylvania, Philadelphia; and6Mona Loufty, Department of Medicine, University of Toronto, Canada
(See the editorial commentary by Altfeld and Goulder, on pages 753–5.)
vaccine, which elicits T cell immunity, can lead to control of human immunodeficiency virus (HIV) replication in
participants who became HIV-infected after vaccination.
Methods.We evaluated the effect of the vaccine on trends in HIV viral load, CD41 T cell counts, time to
initiation of antiretroviral therapy (ART), and AIDS-free survival in 87 male participants who became infected with
HIV during the Step study and who had a median of 24 months of post-infection follow-up.
Results. There was no overall effect of vaccine on mean log10 viral load (estimated difference between
groups, -0.11; P 5 .47). In a subset of subjects with protective HLA types (B27, B57, B58), mean HIV-1 RNA level over
time was lower among vaccine recipients. There was no significant difference in CD41 T cell counts, time to ART
initiation, or in AIDS-free survival between HIV-1–infected subjects who received vaccine versus those who received
Conclusions. HIV RNA levels, CD41 T cell counts, time to initiation of ART, and AIDS-free survival were
similar in vaccine and placebo recipients. There may have been a favorable effect of vaccine on HIV-1 RNA levels in
participants with HLA types associated with better control of HIV-1.
The Step study was a randomized trial to determine whether an adenovirus type 5 (Ad5) vector
Cell-mediated immunity in human immunodefi-
ciency virus (HIV)–infected patients may control viral
replication and slow HIV disease progression [1–8]. In
preclinical primate models, most vaccines that elicit
cell-mediated immunity do not prevent infection,
but they do lower post-infection viral loads and
slow retroviral disease progression [9–11]. Therefore,
a number of HIV-1 vaccine candidates have been
developed that aim to elicit cell-mediated immunity.
The goal of these vaccines is to improve immune
control of viral replication after infection, to decrease
HIV-1 RNA levels, and to thereby slow HIV-1 disease
progression and reduce sexual transmission to others.
The Step study was a randomized trial of the Merck
adenovirus type 5 (Ad5) trivalent HIV-1 vaccine that
was designed to elicit cell-mediated immunity. Three
thousand adults in North America, the Caribbean,
Received 19 May 2010; accepted 17 September 2010.
Potential conflicts of interest: D.M. and M.N.R. are paid employees of Merck,
own Merck stock, and have Merck stock options. All other authors: no conflicts.
Presented in part: Late Breaker Session, Vaccine Effects on HIV-1 Progression in
the Step Study, AIDS Vaccine Conference 2008, Cape Town, South Africa, 13–16
October 2008; Abstract SS01-02, AIDS Vaccine 2009, Paris, France, 19–22 October
aMembers of the study group are listed at the end of the text.
Reprints or correspondence: Daniel Fitzgerald, MD, Center for Global Health,
Weill Cornell Medical College, Rm A-421, 1300 York Ave, New York, NY 10021
The Journal of Infectious Diseases
? The Author 2011. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please
AD5/HIV Vaccine Effect on HIV Progression
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