Amplified antigen-specific immune responses in HIV-1 infected individuals in a double blind DNA immunization and therapy interruption trial |
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Authors: | Gudmundsdotter L Wahren B Haller B K Boberg A Edbäck U Bernasconi D Buttò S Gaines H Imami N Gotch F Lori F Lisziewicz J Sandström E Hejdeman B |
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Affiliation: | a Karolinska Institutet and Swedish Institute for Infectious Disease Control, Nobels väg 18, 171 82 Stockholm, Sweden b Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Solna, Sweden c National AIDS Center, Istituto Superiore di Sanità, Rome, Italy d Department of Immunology, Imperial College London, Chelsea & Westminster Hospital, London, UK e Virostatics srl., Sassari, Italy f Genetic Immunity Kft, Budapest, Hungary g Venhälsan, South Hospital, Stockholm, Sweden |
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Abstract: | Immunotherapy in patients with HIV-1 infection aims to restore and broaden immunological competence, reduce viral load and thereby permit longer periods without combined antiretroviral treatment (cART). Twelve HIV-1-infected patients on cART were immunized on the skin with DNA plasmids containing genes of several HIV-1 subtypes with or without the addition of hydroxyurea (HU), or with placebo. The mean net gain of HIV-specific CD8+ T cell responses were higher and broader in the HIV DNA vaccine groups compared to non-vaccinated individuals (p < 0.05). The vaccine-induced immune responses per se had no direct effect on viral replication. In all patients combined, including placebo, the viral set point after a final structured therapy interruption (STI) was lower than prior to initiation of cART (p = 0.003). Nadir CD4 levels appeared to strongly influence the post-STI viral titers. After the sixth immunization or placebo, patients could stay off cART for a median time of 15 months. The study shows that HIV DNA immunization induces broader and higher magnitudes of HIV-specific immune responses compared to structured therapy interruptions alone. Although compromised by small numbers of patients, the study also demonstrates that well-monitored STI may safely function as an immunological read out of HIV vaccine efficacy. |
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Keywords: | HIV-1 Transdermal therapeutic immunization DNA vaccine |
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