Doravirine is a novel non-
nucleoside reverse transcriptase inhibitor (NNRTI) that has demonstrated good efficacy, tolerability, and safety for the treatment of patients with human immunodeficiency virus (HIV)-1
infection in phase III clinical trials.
Doravirine achieved non-inferiority when compared with
efavirenz- and
darunavir/
ritonavir-based regimens. Fewer adverse effects, including neuropsychiatric effects were observed with
doravirine compared with
efavirenz. Key pharmacodynamic and pharmacokinetic characteristics as well as
drug-drug interactions and the resistance profile were assessed in this clinical review.
Doravirine is a pyridinone NNRTI with potent
antiviral activity against wild-type HIV-1 virus and common NNRTI variants. Studies in healthy volunteers and HIV-infected individuals have shown that
doravirine has a favorable pharmacokinetic profile for once-daily dosing, with an elimination half-life of around 15 h, median time to maximum plasma concentrations of 1-4 h, and time to steady-state concentration of 7 days. The pharmacokinetics of
doravirine are not greatly influenced by sex, age, race, or hepatic impairment. Although no dose adjustment is required for
doravirine in renal impairment when given as a single
tablet, the fixed-dose combination
tablet of
doravirine/
lamivudine/
tenofovir disoproxil fumarate is not recommended in patients with a
creatinine clearance of < 50 mL/min.
Doravirine has a low potential for
drug-drug interactions and does not impact on the pharmacokinetics of other drugs. However, it is metabolized via
cytochrome P450 (CYP) 3A
enzymes and is thus susceptible to interactions with
CYP3A inhibitors and inducers. Strong
CYP3A inhibitors can significantly increase
doravirine exposure; however, this is not considered to be clinically relevant. Conversely, strong
CYP3A inducers, such as
rifampin, are contraindicated with
doravirine owing to a significant reduction in exposure with potential for impaired virological efficacy. Moderate
CYP3A inducers, such as
rifabutin, may be co-administered if the
doravirine dose is increased to 100 mg twice daily.
Doravirine has a unique resistance profile and has demonstrated in vitro activity against some of the most common, clinically relevant NNRTI-resistant mutations. Prevalence of baseline NNRTI resistance to
doravirine appears to be low in treatment-naïve cohorts. Further data on the efficacy of
doravirine in patients with previous treatment experience and/or transmitted NNRTI resistance are required to further inform its place in the current armamentarium of drugs for the treatment of
HIV infection.