Can immunotherapy be useful as a “functional cure” for infection with Human Immunodeficiency Virus-1?

Abstract

Immunotherapy aims to assist the natural immune system in achieving control over viral infection. Various immunotherapy formats have been evaluated in either therapy-naive or therapy-experienced HIV-infected patients over the last 20 years. These formats included non-antigen specific strategies such as cytokines that stimulate immunity or suppress the viral replication, as well as antibodies that block negative regulatory pathways. A number of HIV-specific therapeutic vaccinations have also been proposed, using in vivo injection of inactivated virus, plasmid DNA encoding HIV antigens, or recombinant viral vectors containing HIV genes. A specific format of therapeutic vaccines consists of ex vivo loading of autologous dendritic cells with one of the above mentioned antigenic formats or mRNA encoding HIV antigens.This review provides an extensive overview of the background and rationale of these different therapeutic attempts and discusses the results of trials in the SIV macaque model and in patients. To date success has been limited, which could be explained by insufficient quality or strength of the induced immune responses, incomplete coverage of HIV variability and/or inappropriate immune activation, with ensuing increased susceptibility of target cells.Future attempts at therapeutic vaccination should ideally be performed under the protection of highly active antiretroviral drugs in patients with a recovered immune system. Risks for immune escape should be limited by a better coverage of the HIV variability, using either conserved or mosaic sequences. Appropriate molecular adjuvants should be included to enhance the quality and strength of the responses, without inducing inappropriate immune activation. Finally, to achieve a long-lasting effect on viral control (i.e. a “functional cure”) it is likely that these immune interventions should be combined with anti-latency drugs and/or gene therapy.

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“…This would make this approach particularly interesting and a newly founded biotech, eTheRNA (Prof K. Thielemans, Free University of Brussels, Brussels, Belgium), strives to build on these results. DC-based vaccination approaches have also been suggested as a way to achieve functional cure of human immunodeficiency virus (HIV) when traditional treatment regimens have first largely reduced viral load [Vanham and Van Gulck, 2012]. The principle feasibility of this idea has already been demonstrated in humans .…”

HIV-1 Immunogen: an overview of almost 30 years of clinical testing of a candidate therapeutic vaccine

“…Furthermore, ART does not cure HIV infection since it cannot eliminate latent viral reservoirs [4,5,7,8]. A relatively inexpensive immunotherapy capable of inducing effective immunological control of both replicating and latent HIV would be invaluable, therefore, as it would replace ART for those currently taking it, as well as providing a feasible option for the majority of the world's HIV-infected individuals who do not have access to ART [4][5][6]9].…”

Novel Prospective Treatment Options

“…The immune based therapies involve in enhancing the potency of the immune system to counteract HIV by reducing inflammation, preventing immune activation by HIV-1 or promoting effective immune responses against HIV. The different modalities used to achieve this effect can be broadly classified into non-HIV antigen specific therapies and those which use the HIV antigens ( Table-6) [6,165].…”