Activation of latent human immunodeficiency virus by the histone deacetylase inhibitor panobinostat: a pilot study to assess effects on the central nervous system

Open Forum Infect Dis. 2015 Mar 30;2(1):ofv037. doi: 10.1093/ofid/ofv037. eCollection 2015 Jan.

Abstract

In a substudy of a clinical trial, we assessed whether activation of latent human immunodeficiency virus (HIV) by the histone deacetylase inhibitor panobinostat had detrimental effects on the central nervous system (CNS). Adults infected with HIV received oral panobinostat 20 mg 3 times per week every other week for 8 weeks. In cerebrospinal fluid (CSF), we assayed panobinostat concentration, HIV RNA, and the level of neuroinflammatory or degenerative biomarkers in 11 individuals before and during study therapy. Neither panobinostat nor HIV RNA was detected in CSF. In addition, there was no change from baseline in CSF biomarkers. Thus, panobinostat administration was not associated with CNS adverse effects as assessed by CSF biomarkers.

Keywords: central nervous system; cerebrospinal fluid; histone deacetylase inhibitors; human immunodeficiency virus; panobinostat.