Safety and Immunogenicity of Therapeutic DNA
Vaccination in Individuals Treated with Antiretroviral
Therapy during Acute/Early HIV-1 Infection
Eric S. Rosenberg1*, Barney S. Graham2, Ellen S. Chan3, Ronald J. Bosch3, Vicki Stocker4, Janine Maenza5,
Martin Markowitz6, Susan Little7, Paul E. Sax8, Ann C. Collier5, Gary Nabel2, Suzanne Saindon1, Theresa
Flynn1, Daniel Kuritzkes8, Dan H. Barouch9, for the ACTG A5187 Team
1Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 2Vaccine Research Center, National Institute of Allergy
and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 3Harvard School of Public Health, Boston, Massachusetts, United
States of America, 4Social and Scientific Systems, Silver Spring, Maryland, United States of America, 5University of Washington, Seattle, Washington, United States of
America, 6Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York, United States of America, 7University of California San Diego, San Diego,
California, United States of America, 8Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 9Beth Israel
Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America
Background: An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or
delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG) A5187 was a phase I/II, randomized, placebo-
controlled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00-
VP) in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099)
Methods: Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1
infection and had HIV-1 RNA,50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this
study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted
antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17–23 weeks after treatment
Results: Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject
met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine
versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following
treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo
recipients were 3.5 and 3.7 log10HIV-1 RNA copies/mL, respectively.
Conclusions: The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP) was safe but poorly immunogenic in subjects treated with
antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo
recipients following treatment interruption. However, median viral load set-points in both groups were lower than in
historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and
supporting the safety of discontinuing treatment in this group.
Trial Registration: Clinicaltrials.gov NCT00125099
Citation: Rosenberg ES, Graham BS, Chan ES, Bosch RJ, Stocker V, et al. (2010) Safety and Immunogenicity of Therapeutic DNA Vaccination in Individuals Treated
with Antiretroviral Therapy during Acute/Early HIV-1 Infection. PLoS ONE 5(5): e10555. doi:10.1371/journal.pone.0010555
Editor: Mario A. Ostrowski, University of Toronto, Canada
Received December 16, 2009; Accepted April 1, 2010; Published May 10, 2010
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public
domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Funding: NIH AIDS Clinical Trials Group (ACTG, AI068636, AI068634, AI038858, AI038855), Doris Duke Clinical Scientist Development Award (D.H.B.), and NIH
grants AI058727, AI066305, AI066924, AI078526 (D.H.B.) and AI 40873 (E.S.R). The funders had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: firstname.lastname@example.org
Despite the striking decline in morbidity and mortality in
persons receiving antiretroviral therapy , the short- and long-
term toxicities, increasing drug resistance, challenges with
adherence, and cost make the prospect of long-term therapy
difficult for many HIV-1 infected individuals. More importantly,
the majority of HIV-1 infected individuals live in developing
countries with limited access to antiretroviral therapy. An effective
therapeutic vaccine that could induce or augment HIV-1-specific
immune responses may potentially delay or reduce the need for
One approach to inducing HIV-1-specific immunity is through
the delivery of multiple viral antigens by DNA plasmids. The DNA
PLoS ONE | www.plosone.org1 May 2010 | Volume 5 | Issue 5 | e10555
suggest a possible role of antiretroviral therapy in persons with
acute and early HIV-1 infection and indicate that further studies
should be performed to determine if such therapy is beneficial.
Therapeutic vaccine studies utilizing more potent HIV-1 vaccine
candidates should also be considered.
Found at: doi:10.1371/journal.pone.0010555.s001 (0.60 MB
Found at: doi:10.1371/journal.pone.0010555.s002 (0.19 MB
We thank the study volunteers and thank and acknowledge:
Amy Sbrolla, RN -Massachusetts General Hospital (Site 101)
Ann C. Collier, M.D.- University of Washington Primary Infection Clinic
Paul Edward Sax, M.D. and Jon Gothing, A.C.R.N., B.S.N., R.N.-
Brigham and Women’s Hospital (Site 107)
Paula Potter, R.N. and Tari Gilbert, F.N.P.-USCD (Site 701)
Aaron Diamond AIDS Research Center (Site AI-401)
Michael Kishko, Kara O’Brien, Beth Israel Deaconess Medical Center
AIDS Clinical Trials Network
AIDS Clinical Trials Statistical and Data Analysis Center
Conceived and designed the experiments: ESR BSG ESC RJB VS MM SL
GJN DRK DHB. Performed the experiments: ESR BSG JM MM PS AC
SS DHB. Analyzed the data: ESR ESC RJB. Contributed reagents/
materials/analysis tools: BSG GJN DHB. Wrote the paper: ESR. Served as
clinical trial specialist: VS. Site PI: JM SL PS AC. Contributed vaccine:
GJN. Clinical specialist/Field representative: TF. PI of HARVARD
ACTU: DRK. Co-Chair of study: DHB.
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Figure 5. Lymphocyte proliferation responses (Stimulation Index) by antigen and treatment arm. Antiretroviral therapy was
discontinued at study week 30. The symbol V indicates when vaccine or placebo was administered. The shaded area indicates the time period when
subjects were off antiretroviral therapy.
Vaccination in HIV-1 Infection
PLoS ONE | www.plosone.org7May 2010 | Volume 5 | Issue 5 | e10555