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HIV Eradication: Combinatorial Approaches to Activate Latent Viruses

The concept of eradication of the Human Immune Deficiency Virus (HIV) from infected patients has gained much attention in the last few years. While combination Anti-Retroviral Therapy (c-ART) has been extremely effective in suppressing viral replication, it is not curative. This is due to the presen...

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Autores principales: De Crignis, Elisa, Mahmoudi, Tokameh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246239/
https://www.ncbi.nlm.nih.gov/pubmed/25421889
http://dx.doi.org/10.3390/v6114581
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author De Crignis, Elisa
Mahmoudi, Tokameh
author_facet De Crignis, Elisa
Mahmoudi, Tokameh
author_sort De Crignis, Elisa
collection PubMed
description The concept of eradication of the Human Immune Deficiency Virus (HIV) from infected patients has gained much attention in the last few years. While combination Anti-Retroviral Therapy (c-ART) has been extremely effective in suppressing viral replication, it is not curative. This is due to the presence of a reservoir of latent HIV infected cells, which persist in the presence of c-ART. Recently, pharmaceutical approaches have focused on the development of molecules able to induce HIV-1 replication from latently infected cells in order to render them susceptible to viral cytopathic effects and host immune responses. Alternative pathways and transcription complexes function to regulate the activity of the HIV promoter and might serve as molecular targets for compounds to activate latent HIV. A combined therapy coupling various depressors and activators will likely be the most effective in promoting HIV replication while avoiding pleiotropic effects at the cellular level. Moreover, in light of differences among HIV subtypes and variability in integration sites, the combination of multiple agents targeting multiple pathways will increase likelihood of therapeutic effectiveness and prevent mutational escape. This review provides an overview of the mechanisms that can be targeted to induce HIV activation focusing on potential combinatorial approaches.
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spelling pubmed-42462392014-12-01 HIV Eradication: Combinatorial Approaches to Activate Latent Viruses De Crignis, Elisa Mahmoudi, Tokameh Viruses Review The concept of eradication of the Human Immune Deficiency Virus (HIV) from infected patients has gained much attention in the last few years. While combination Anti-Retroviral Therapy (c-ART) has been extremely effective in suppressing viral replication, it is not curative. This is due to the presence of a reservoir of latent HIV infected cells, which persist in the presence of c-ART. Recently, pharmaceutical approaches have focused on the development of molecules able to induce HIV-1 replication from latently infected cells in order to render them susceptible to viral cytopathic effects and host immune responses. Alternative pathways and transcription complexes function to regulate the activity of the HIV promoter and might serve as molecular targets for compounds to activate latent HIV. A combined therapy coupling various depressors and activators will likely be the most effective in promoting HIV replication while avoiding pleiotropic effects at the cellular level. Moreover, in light of differences among HIV subtypes and variability in integration sites, the combination of multiple agents targeting multiple pathways will increase likelihood of therapeutic effectiveness and prevent mutational escape. This review provides an overview of the mechanisms that can be targeted to induce HIV activation focusing on potential combinatorial approaches. MDPI 2014-11-21 /pmc/articles/PMC4246239/ /pubmed/25421889 http://dx.doi.org/10.3390/v6114581 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
De Crignis, Elisa
Mahmoudi, Tokameh
HIV Eradication: Combinatorial Approaches to Activate Latent Viruses
title HIV Eradication: Combinatorial Approaches to Activate Latent Viruses
title_full HIV Eradication: Combinatorial Approaches to Activate Latent Viruses
title_fullStr HIV Eradication: Combinatorial Approaches to Activate Latent Viruses
title_full_unstemmed HIV Eradication: Combinatorial Approaches to Activate Latent Viruses
title_short HIV Eradication: Combinatorial Approaches to Activate Latent Viruses
title_sort hiv eradication: combinatorial approaches to activate latent viruses
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4246239/
https://www.ncbi.nlm.nih.gov/pubmed/25421889
http://dx.doi.org/10.3390/v6114581
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