Article

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

ABSTRACT 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)
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.
Clinicaltrials.gov NCT00125099.

0 Followers
 · 
121 Views
  • Source
    • "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). "
    HIV and AIDS - Updates on Biology, Immunology, Epidemiology and Treatment Strategies, 10/2011; , ISBN: 978-953-307-665-2
  • Value in Health 11/2006; 9(6). DOI:10.1016/S1098-3015(10)63251-2 · 2.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: HIV infection can persist in spite of efficacious antiretroviral therapies. Although incomplete inhibition of viral replication may contribute to this phenomenon, this is largely due to the early establishment of a stable reservoir of latently infected cells. Thus, life-long antiviral therapy may be needed to control HIV. Such therapy is prone to drug resistance and cumulative side effects and is an unbearable financial burden for regions of the world hit hardest by the epidemic. This review discusses our current understanding of HIV persistence and the limitations of potential approaches to eradicate the virus and accordingly pleads for a joint multidisciplinary effort toward two highly related goals: the development of an HIV prophylactic vaccine and the achievement of long-term drug-free remissions in HIV-infected individuals.
    Science 07/2010; 329(5988):174-80. DOI:10.1126/science.1191047 · 31.48 Impact Factor
Show more

Preview (2 Sources)

Download
0 Downloads
Available from