par Bouchat, Sophie ;Delacourt, Nadège ;Kula, Anna ;Darcis, Gilles ;Van Driessche, Benoît ;Corazza, Francis ;Gatot, Jean-Stéphane ;Melard, Adeline;Vanhulle, Caroline ;Kabeya, Kabamba ;Pardons, Marion;Avettand-Fenoel, Veronique;Clumeck, Nathan ;De Wit, Stéphane ;Rohr, Olivier;Rouzioux, Christine;Van Lint, Carine
Référence EMBO molecular medicine, 8, 2, page (117-138)
Publication Publié, 2016-02
Référence EMBO molecular medicine, 8, 2, page (117-138)
Publication Publié, 2016-02
Article révisé par les pairs
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. |