STATE OF THE ART
Despite current effective and life-prolonging cART, HIV-1 can still not be cured. Indeed, the persistence of latently-infected resting CD4+ T cells harboring transcriptionally silent but replication competent HIV-1 proviruses seriously challenge the hope of HIV-1 eradication from cART-treated HIV-1 infected patients. Reactivation of HIV-1 expression in reservoirs together with an efficient cART has been proposed as an adjuvant therapy aimed at reaching a functional cure.
Several studies have identified individual compounds that are capable of reversing HIV-1 latency and several clinical trials have started. However, these studies question the efficiency of these drugs used alone and underly the importance to further test other classes of HIV-1 inducers, alone or in combination, to reduce the HIV-1 reservoirs.
The combined use of two drugs to activate latent HIV could cause a synergistic reactivation of HIV-1 production. Indeed, a proof-of-concept has been demonstrated by inventors for the coadministration of two different types of therapeutically promising HIV-1 inducers [DNA methylation inhibitors in combination with histone deacethylase inhibitors (HDACis) or histone methyltransferase inhibitors (HMTis) in combination with HDACi or NF-kappaB inducers] together with efficient cART as a therapeutic perspective to decrease the pool of latent HIV-1 reservoirs.
As selected molecules are already promising candidates or accepted in human clinical trials or therapies for other diseases, a clinical phase Ib/II has been launched. The cART therapy is the only treatment currently available for AIDS and our current approach is innovative, no competition exists for the moment in this competitive market.
KEY ADVANTAGES OF THE TECHNOLOGY
Obtaining a regimen to eliminate the latent compartment of HIV-1 and stop cART therapies may:
limit exposure to the anti-AIDS molecules, thereby limiting side effects
the life quality of the patients would be greatly improved.
reduce the care costs for HIV+ patients.
MAIN PUBLICATIONS (related to this technology)
- Histone methyltransferase inhibitors induce HIV-1 recovery in resting CD4+ T cells from HIV-1+ HAART-treated patients. Bouchat S, Gatot JS, Kabeya K, Cardona C, Colin L, Herbein G, de Wit S, Clumeck N, Lambotte O, Rouzioux C, Rohr O, Van Lint C - Aids 2012, 26:1473-82. IF : 6,245
- HIV-1 transcription and latency: an update. Van Lint C, Bouchat S, Marcello A. Retrovirology 2013, 10: 67. IF: 5,660