Therapeutic Vaccine for HIV

The advent of combination antiretroviral therapy (cART) has dramatically improved the clinical outcome in human immunodeficiency virus (HIV)-infected individuals through sustained reduction in viral replication. However, it has become clear that cART alone cannot eradicate HIV in infected individuals, likely in part due to the persistence of viral reservoirs in peripheral blood and various tissue compartments. Consequently, a major thrust of HIV research over the past several years has been to develop therapeutic strategies that can eliminate persistent viral reservoirs and boost host immunity to control viral replication upon discontinuation of cART. Therapeutic HIV vaccination is one approach that could potentially achieve these goals through vaccine-induced improvement in HIV-specific immune responses and/or by direct reactivation of HIV-specific CD4+ memory T cells that harbor latent HIV. An effective therapeutic vaccine could augment immunologic control of HIV infection and potentially obviate the need for chronic cART. The current study is an exploratory randomized, 2-arm (1:1), double-blind, placebo-controlled trial evaluating the safety and efficacy of an HIV-1 multiantigen plasmid DNA (HIV-MAG pDNA) vaccine prime in combination with an interleukin-12 plasmid DNA (IL-12 pDNA) adjuvant delivered by in vivo electroporation followed by a recombinant vesicular stomatitis virus vector containing the HIV-1 gag gene (rVSV HIV gag) booster vaccine in subjects on cART who started therapy during acute or early HIV infection. Subjects will be randomized to receive placebo or the HIV-MAG pDNA (3000 g) vaccine prime and IL-12 pDNA adjuvant (1000 g) at week 0, 4, 12, and 36, and the rVSV HIV gag booster vaccine (1x107 plaque-forming units) at week 24 and 48. The HIV-MAG pDNA vaccine prime and IL-12 pDNA adjuvant will be administered as 2 IM injections, 1 into each deltoid, with electroporation using the Ichor TDS device, while the rVSV HIV gag booster vaccine will be administered as 2 conventional IM injections, 1 into each deltoid. After the week 56 visit, all subjects will undergo an analytical treatment interruption to determine if the vaccination strategy results in an improved immune control of viral replication, as evidenced by a blunted or absent rebound in HIV plasma viremia. All subjects will be followed through week 96 for safety and efficacy parameters. The study population includes HIV-infected adults who began cART during acute or early infection. Subjects must be receiving an effective cART regimen, with a CD4 cell count of \>450 cells/mm3 at screening, and they must have documented viral suppression below the limit of detection for greater than1 year. The rationale for testing the study vaccine regimen in this subject population is because these individuals may have a relatively preserved immune function, which could be augmented by therapeutic vaccination.