title: Targeting the Brain Reservoirs: Toward an HIV Cure.
abstract: One of the top research priorities of the international AIDS society by the action "Towards an HIV Cure" is the purge or the decrease of the pool of all latently infected cells. This strategy is based on reactivation of latently reservoirs (the shock) followed by an intensifying combination antiretroviral therapy (cART) to kill them (the kill). The central nervous system (CNS) has potential latently infected cells, i.e., perivascular macrophages, microglial cells, and astrocytes that will need to be eliminated. However, the CNS has several characteristics that may preclude the achievement of a cure. In this review, we discuss several limitations to the eradication of brain reservoirs and how we could circumvent these limitations by making it efforts in four directions: (i) designing efficient latency-reversal agents for CNS-cell types, (ii) improving cART by targeting HIV transcription, (iii) improving delivery of HIV drugs in the CNS and in the CNS-cell types, and (iv) developing therapeutic immunization. As a prerequisite to these efforts, we also believe that a better comprehension of molecular mechanisms involved in establishment and persistence of HIV latency in brain reservoirs are essential to design new molecules for strategies aiming to achieve a cure for instance the "shock and kill" strategy.
authors.affiliation: INSERM UMR 1121 Faculté de Chirurgie Dentaire, Université de Strasbourg , Strasbourg , France.
authors.forename: Céline
authors.initials: C
authors.lastname: Marban
authors.affiliation: EA7292, DHPI, Université de Strasbourg , Strasbourg , France.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Forouzanfar
authors.affiliation: EA7292, DHPI, Université de Strasbourg , Strasbourg , France.
authors.forename: Amina
authors.initials: A
authors.lastname: Ait-Ammar
authors.affiliation: EA7292, DHPI, Université de Strasbourg , Strasbourg , France.
authors.forename: Faiza
authors.initials: F
authors.lastname: Fahmi
authors.affiliation: EA7292, DHPI, Université de Strasbourg, Strasbourg, France; IUT Louis Pasteur de Schiltigheim, Université de Strasbourg, Schiltigheim, France.
authors.forename: Hala
authors.initials: H
authors.lastname: El Mekdad
authors.affiliation: EA7292, DHPI, Université de Strasbourg , Strasbourg , France.
authors.forename: Fadoua
authors.initials: F
authors.lastname: Daouad
authors.affiliation: EA7292, DHPI, Université de Strasbourg, Strasbourg, France; IUT Louis Pasteur de Schiltigheim, Université de Strasbourg, Schiltigheim, France; Institut Universitaire de France, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rohr
authors.affiliation: EA7292, DHPI, Université de Strasbourg, Strasbourg, France; IUT Louis Pasteur de Schiltigheim, Université de Strasbourg, Schiltigheim, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Schwartz
keywords: HIV transcription; brain; cART; cure; latency; reservoirs