Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial.

ABSTRACT: Disulfiram (DSF) was well tolerated and activated viral transcription (cell-associated unspliced (CA-US) and plasma human immunodeficiency virus (HIV) RNA) in a phase II dose-escalation trial in HIV+ antiretroviral therapy (ART)-suppressed participants. Here, we investigated whether exposure to DSF and its metabolites predicted these changes in HIV transcription. Participants were administered 500 (N = 10), 1,000 (N = 10), or 2,000 (N = 10) mg of DSF for 3 consecutive days. DSF and four metabolites were measured by ultraperformance liquid chromatography-tandem mass spectrometry. Changes in CA-US and plasma HIV RNA were quantified by polymerase chain reaction (PCR) and analyzed in NONMEM. A seven-compartment pharmacokinetic (PK) model demonstrated nonlinear elimination kinetics. The fitted

SUBMITTER: Lee SA 

PROVIDER: S-EPMC6379104 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature