Safety and Immunogenicity of Therapeutic DNA Vaccination in Individuals Treated with Antiretroviral Therapy during Acute/Early HIV-1 Infection

University of Toronto, Canada
PLoS ONE (Impact Factor: 3.23). 05/2010; 5(5):e10555. DOI: 10.1371/journal.pone.0010555
Source: PubMed


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. ( NCT00125099)
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.
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.
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. NCT00125099.

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    • "Therefore, an alternative goal is a functional cure, in which virus is not eliminated but is controlled sufficiently by antiviral immune responses so that drug treatment can be withdrawn for prolonged periods of time [4]. Because withdrawal of ART generally leads to a rapid viral rebound, a variety of interventions have been explored to boost immunological control prior to ART withdrawal; these strategies include structured treatment interruptions, active immunization and immune reconstitution strategies [5-8]. While many of these strategies showed some modest efficacy, the benefits were often variable or transient, or the strategy was technically challenging. "
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    • "viral proteins used for immunotherapy include the viral envelope protein, core protein (Gag), reverse transcriptase, tat, nef, polymerase, as well as the whole killed virus (Tsoukas, Raboud et al. 1998; Gorse, Simionescu et al. 2006; Ensoli, Bellino et al. 2010). Viral proteins have been delivered as recombinant proteins, DNA vaccines, on virus-like-particles or in viral vectors (Buonaguro, Tornesello et al. 2009; Rosenberg, Graham et al. 2010). CD8+ T cells with cytolytic activity appeared to control viral titers in both non-human primate models, as well as infected individuals with HIV (O'Connell, Bailey et al. 2009). "
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