title: Immunological and pharmacological strategies to reactivate HIV-1 from latently infected cells: a possibility for HIV-1 paediatric patients?
abstract: The limitations to establishing a viral reservoir facilitated by early cART in children could play a critical role in achieving natural control of viral replication upon discontinuation of cART, which could be defined as 'functional cure'. Viral reservoirs could provide a persistent source of recrudescent viraemia after withdrawal of cART, despite temporary remission of HIV-1 infection, as observed in the 'Mississippi baby'. Intensification of cART has been proposed as a strategy to control residual replication and to diminish the reservoirs. The effects of cART intensification with maraviroc persisted after discontinuation of the drug in HIV-1-infected adults. However, in HIV-1-infected children, the emergence of CXCR4-using variants occurs very early, and the use of CCR5 antagonists in these children as intensification therapy may not be the best alternative. New treatments to eradicate HIV-1 are focused on the activation of viral production from latently infected cells to purge and clear HIV-1 reservoirs. This strategy involves the use of a wide range of small molecules called latency-reversing agents (LRAs). Histone deacetylase inhibitors (HDACi) such as givinostat, belinostat and panobinostat, and class I-selective HDACis that include oxamflatin, NCH-51 and romidepsin, are the most advanced in clinical testing for HIV-1 LRAs. Panobinostat and romidepsin show an efficient reactivation profile in J89GFP cells, a lymphocyte HIV-1 latently infected cell line considered a relevant model to study post-integration HIV-1 latency and reactivation. Clinical trials with panobinostat and romidepsin have been performed in children with other pathologies and it could be reasonable to design a clinical trial using these drugs in combination with cART in HIV-1-infected children.
authors.affiliation: Servicio de Inmunología, Laboratorio InmunoBiología Molecular , Hospital General Universitario Gregorio Marañón , Madrid , Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martínez-Bonet
authors.affiliation: Servicio de Inmunología, Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Plataforma de Cultivos Celulares, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain.
authors.forename: M I
authors.initials: MI
authors.lastname: Clemente
authors.affiliation: Servicio de Inmunología, Laboratorio InmunoBiología Molecular , Hospital General Universitario Gregorio Marañón , Madrid , Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Serramía
authors.affiliation: Servicio de Enfermedades Infecciosas , Hospital Universitario Ramón y Cajal and IRYCIS , Madrid , Spain.
authors.forename: S
authors.initials: S
authors.lastname: Moreno
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigaciones Biomédicas de Córdoba (IMIBIC), Reina Sofia University Hospital , University of Córdoba , Córdoba , Spain.
authors.forename: E
authors.initials: E
authors.lastname: Muñoz
authors.affiliation: Servicio de Inmunología, Laboratorio InmunoBiología Molecular , Hospital General Universitario Gregorio Marañón , Madrid , Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Muñoz-Fernández
keywords: HIV-latency; HIV-reactivation; panobinostat; romidepsin; vertically acquired HIV-1 infection