Abstract
BackgroundAn 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)MethodsTwenty 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.ResultsTwenty 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 log10 HIV-1 RNA copies/mL, respectively.ConclusionsThe 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 RegistrationClinicaltrials.gov NCT00125099
Highlights
Despite the striking decline in morbidity and mortality in persons receiving antiretroviral therapy [1], the short- and longterm toxicities, increasing drug resistance, challenges with adherence, and cost make the prospect of long-term therapy difficult for many HIV-1 infected individuals
The vaccine induced significant cellular and humoral immune responses. Because this vaccine appeared safe and immunogenic in HIV-1-uninfected adults, we assessed the potential utility of this vaccine in healthy HIV-1-infected individuals
Participant Selection Twenty healthy HIV-1 infected adults, aged 26–47, who were treated with antiretroviral therapy during acute or early HIV-1 infection participated in this study
Summary
Despite the striking decline in morbidity and mortality in persons receiving antiretroviral therapy [1], the short- and longterm toxicities, increasing drug resistance, challenges with adherence, and cost make the prospect of long-term therapy difficult for many HIV-1 infected individuals. An effective therapeutic vaccine that could induce or augment HIV-1-specific immune responses may potentially delay or reduce the need for antiretroviral therapy. The DNA vaccine VRC-HIVDNA009-00-VP is a 4 plasmid mixture encoding a subtype B Gag-Pol-Nef fusion protein and modified envelope (Env) constructs from HIV-1 subtypes A, B and C. This multiclade DNA vaccine has previously been evaluated in a phase I dose escalation study in healthy, HIV-1-uninfected adults and was found to be safe and well tolerated[2]. The vaccine induced significant cellular and humoral immune responses Because this vaccine appeared safe and immunogenic in HIV-1-uninfected adults, we assessed the potential utility of this vaccine in healthy HIV-1-infected individuals. AIDS Clinical Trials Group (ACTG) A5187 was a phase I/II, randomized, placebocontrolled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00VP) in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099)
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