Alexander J Stockdale1, Saye Khoo2. 1. Institute of Infection, Veterinary and Ecological Sciences. 2. Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Abstract
PURPOSE OF REVIEW: We reviewed evidence concerning the novel nonnucleoside reverse transcriptase inhibitor doravirine, aiming to identify situations where it may be selected in preference to integrase inhibitors. RECENT FINDINGS: Doravirine is licenced for the treatment of HIV-1 in North America and Europe. In two multicentre randomized controlled trials, noninferiority with comparator drugs efavirenz and darunavir/ritonavir was observed at 96 weeks. Doravirine is associated with a lower incidence of neuropsychiatric side effects relative to efavirenz, and favourable lipid changes relative to darunavir over 96 weeks. A lower incidence of weight gain, relative to indirect comparisons with integrase inhibitors, was observed. Doravirine has a high genetic barrier to resistance with retained activity in the presence of single NNRTI mutations K103N, Y181C and G190A. Primary drug resistance is infrequent and may be higher in South Africa relative to European populations. Doravirine may be used in renal or hepatic impairment and has a low potential for drug-drug interactions. SUMMARY: Doravirine is a well tolerated and effective agent in ART-naive patients. Direct comparison with integrase inhibitors, and evidence on the outcomes of treatment with doravirine in the presence of prior NNRTI experience are required to better elucidate which patients will benefit most from doravirine therapy.
PURPOSE OF REVIEW: We reviewed evidence concerning the novel nonnucleoside reverse transcriptase inhibitor doravirine, aiming to identify situations where it may be selected in preference to integrase inhibitors. RECENT FINDINGS: Doravirine is licenced for the treatment of HIV-1 in North America and Europe. In two multicentre randomized controlled trials, noninferiority with comparator drugs efavirenz and darunavir/ritonavir was observed at 96 weeks. Doravirine is associated with a lower incidence of neuropsychiatric side effects relative to efavirenz, and favourable lipid changes relative to darunavir over 96 weeks. A lower incidence of weight gain, relative to indirect comparisons with integrase inhibitors, was observed. Doravirine has a high genetic barrier to resistance with retained activity in the presence of single NNRTI mutations K103N, Y181C and G190A. Primary drug resistance is infrequent and may be higher in South Africa relative to European populations. Doravirine may be used in renal or hepatic impairment and has a low potential for drug-drug interactions. SUMMARY: Doravirine is a well tolerated and effective agent in ART-naive patients. Direct comparison with integrase inhibitors, and evidence on the outcomes of treatment with doravirine in the presence of prior NNRTI experience are required to better elucidate which patients will benefit most from doravirine therapy.
Authors: Maria Mazzitelli; Melania Degli Antoni; Francesco Castelli; Diego Ripamonti; Gianluca Zuglian; Giuseppe Lapadula; Massimiliano Fabbiani; Alice Ferraresi; Cristina Putaggio; Anna Maria Cattelan; Eugenia Quiros-Roldan Journal: Medicine (Baltimore) Date: 2022-07-29 Impact factor: 1.817