Resolution of Neuropsychiatric Adverse Events After Switching to a Doravirine-Based Regimen in the Open-Label Extensions of the DRIVE-AHEAD and DRIVE-FORWARD Trials.

Abstract

Background: Neuropsychiatric adverse events (NPAEs) are associated with several antiretrovirals. Doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor indicated for HIV-1 treatment, does not interact significantly with known neurotransmitter receptors in vitro. First-line therapy with DOR-based regimens resulted in significantly fewer NPAEs than efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) and similar rates to those of ritonavir-boosted darunavir (DRV/r) with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) through Week 96 of the phase 3 DRIVE-AHEAD and DRIVE-FORWARD studies, respectively.

Methods: In DRIVE-AHEAD (NCT02403674) and DRIVE-FORWARD (NCT02275780), treatment-naive adults randomly received DOR/lamivudine/TDF or EFV/FTC/TDF and DOR + 2 NRTIs or DRV/r + 2 NRTIs, respectively, for a 96-week double-blind phase; afterward, participants could continue or switch to a DOR-based regimen for a 96-week open-label extension.

Results: Overall, 269 and 233 participants in DRIVE-AHEAD and DRIVE-FORWARD, respectively, switched to a DOR-based regimen. At Week 96, 26 and 15 participants randomized to EFV/FTC/TDF and DRV/r + 2 NRTIs, respectively, had ongoing NPAEs, resolving by Week 192 in 73% (19/26) and 40% (6/15) of participants switching to a DOR-based regimen. New-onset NPAEs were reported by 9% (25/269) and 8% (18/233) of participants; by Week 192, new-onset NPAEs were resolved and/or resolving in 60% (15/25) and 61% (11/18) of participants.

Conclusions: In both trial extensions, NPAEs persisted in 3-4% of participants 96 weeks after switching to a DOR-based regimen, possibly representing the background rate for these events. This suggests DOR-based therapy may be a good option for adults with baseline neuropsychiatric symptoms or those experiencing NPAEs with other antiretrovirals.