Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection.

TitleSafety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection.
Publication TypeJournal Article
Year of Publication2010
AuthorsRosenberg ES, Graham BS, Chan ES, Bosch RJ, Stocker V, Maenza J, Markowitz M, Little S, Sax PE, Collier AC, Nabel G, Saindon S, Flynn T, Kuritzkes D, Barouch DH
Corporate AuthorsAIDS Clinical Trials Group A5187 Team
JournalPLoS One
Volume5
Issue5
Paginatione10555
Date Published2010
ISSN1932-6203
KeywordsAcute Disease, Adult, AIDS Vaccines, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, HIV Infections, HIV-1, Humans, Interferon-gamma, Male, Middle Aged, RNA, Viral, Vaccination, Vaccines, DNA
Abstract

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 discontinuation.

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 log(10) HIV-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.

DOI10.1371/journal.pone.0010555
Alternate JournalPLoS ONE
PubMed ID20479938
PubMed Central IDPMC2866663
Grant ListAI 40873 / AI / NIAID NIH HHS / United States
AI038855 / AI / NIAID NIH HHS / United States
AI038858 / AI / NIAID NIH HHS / United States
AI058727 / AI / NIAID NIH HHS / United States
AI066305 / AI / NIAID NIH HHS / United States
AI066924 / AI / NIAID NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
AI068636 / AI / NIAID NIH HHS / United States
AI078526 / AI / NIAID NIH HHS / United States