Sequential treatment with 5-aza-2'-deoxycytidine and deacetylase inhibitors reactivates HIV-1 - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue EMBO Molecular Medicine Année : 2015

Sequential treatment with 5-aza-2'-deoxycytidine and deacetylase inhibitors reactivates HIV-1

Résumé

Reactivation of HIV gene expression in latently infected cells together with an efficient cART has been proposed as an adjuvant therapy aimed at eliminating/decreasing the reservoir size. Results from HIV clinical trials using deacetylase inhibitors (HDACIs) question the efficiency of these latency-reversing agents (LRAs) used alone and underline the need to evaluate other LRAs in combination with HDACIs. Here, we evaluated the therapeutic potential of a demethylating agent (5-AzadC) in combination with clinically tolerable HDACIs in reactivating HIV-1 from latency first in vitro and next ex vivo. We showed that a sequential treatment with 5-AzadC and HDACIs was more effective than the corresponding simultaneous treatment both in vitro and ex vivo. Interestingly, only two of the sequential LRA combinatory treatments tested induced HIV-1 particle recovery in a higher manner than the drugs alone ex vivo and at concentrations lower than the human tolerable plasmatic concentrations. Taken together, our data reveal the benefit of using combinations of 5-AzadC with an HDACI and, for the first time, the importance of treatment time schedule for LRA combinations in order to reactivate HIV.
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Dates et versions

hal-02270152 , version 1 (23-08-2019)

Identifiants

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Sophie Bouchat, Nadège Delacourt, Anna Kula, Gilles Darcis, Benoit van Driessche, et al.. Sequential treatment with 5-aza-2'-deoxycytidine and deacetylase inhibitors reactivates HIV-1. EMBO Molecular Medicine, 2015, 8 (2), pp.117-138. ⟨10.15252/emmm.201505557⟩. ⟨hal-02270152⟩

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