Viruses 2014, 6(11), 4581-4608; doi:10.3390/v6114581
HIV Eradication: Combinatorial Approaches to Activate Latent Viruses
Department of Biochemistry, Erasmus University Medical Center, Rotterdam 3015 CN, The Netherlands
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Received: 16 September 2014 / Revised: 1 November 2014 / Accepted: 13 November 2014 / Published: 21 November 2014
(This article belongs to the Special Issue HIV Latency)
Abstract
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. View Full-TextKeywords:
HIV latency; latency reversing agents; shock and kill strategy; HIV transcription regulators
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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MDPI and ACS Style
De Crignis, E.; Mahmoudi, T. HIV Eradication: Combinatorial Approaches to Activate Latent Viruses. Viruses 2014, 6, 4581-4608.