Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy

摘要: Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs) are important maintaining latency and deacetylase inhibitors (HDACi) may reverse by activating transcription from T-cells. We performed a single arm, open label, proof-of-concept study which vorinostat, pan-HDACi, was administered 400 mg orally once daily for 14 days 20 HIV-infected individuals on suppressive antiretroviral therapy (ART). The primary endpoint change cell associated unspliced (CA-US) RNA total blood at day 14. registered ClinicalTrials.gov (NCT01365065). Vorinostat safe well tolerated there were no dose modifications or drug discontinuations. CA-US increased significantly 18/20 patients (90%) with median fold baseline peak value of 7.4 (IQR 3.4, 9.1). elevated 8 hours post remained 70 after last dose. Significant early changes expression genes chromatin remodeling activation correlated magnitude RNA. There statistically significant plasma RNA, concentration DNA, integrated inducible markers T-cell activation. induced sustained increase majority patients. However, additional interventions will be needed efficiently induce production ultimately eliminate cells.