Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial

A Study to Evaluate Doravirine Pharmacokinetics When Coadministered With Acid‐Reducing Agents

“…Doravirine is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral therapy (ART). 1,2 Phase 3 trials in ART-naive adults with HIV-1 infection demonstrated noninferior antiretroviral efficacy in week 48 for doravirine compared with ritonavir-boosted darunavir, both in combination with 2 nucleoside reverse transcriptase inhibitors 3 and for doravirine/lamivudine/tenofovir disoproxil fumarate compared with efavirenz/emtricitabine/tenofovir disoproxil fumarate. 4 Doravirine combinations were generally well tolerated, with demonstration of superior lipid profiles in both studies and fewer neuropsychiatric events compared with efavirenz.…”

“…4 Doravirine combinations were generally well tolerated, with demonstration of superior lipid profiles in both studies and fewer neuropsychiatric events compared with efavirenz. 3,4 Many patients with HIV-1 infection require treatment with gastric acid-reducing agents to alleviate gastrointestinal comorbidities, 5-7 but significant drug interactions have been documented between these agents and ART. For example, plasma drug concentrations of the NNRTI rilpivirine, the HIV integrase strand transferase inhibitor, dolutegravir, and some protease inhibitors are reduced with coadministration of acid-reducing agents, and in many instances, coadministration is restricted or contraindicated.…”

Evaluation of the Pharmacokinetic Interaction Between Doravirine and Methadone

“…12 The stereoselective nature of methadone's metabolism appears to result in different plasma half-life for the R-and Senantiomers. [14][15][16][17] In the United States, doravirine is indicated for administration once daily at a dose of 100 mg, in combination with other antiretroviral agents, for the treatment of HIV-1 infection. 13 Doravirine is a novel nonnucleoside reverse transcriptase inhibitor designed to overcome the limitations of other drugs within the same class.…”

“…10 In one study, the half-life of the R-and S-forms of methadone was reported to be 37.5 and 28.6 hours, respectively. 14,15 To date, preclinical and clinical data suggest that doravirine has minimal drug-drug interactions (DDIs) [18][19][20][21][22] as doravirine is not expected to either induce or inhibit any of the major CYP enzymes or transporters. 14,15 Phase 2 and 3 trials in treatment-naïve HIV-1-infected adults have shown that doravirine in combination with other antiretroviral agents is noninferior in terms of efficacy, but also demonstrates a more favorable safety profile compared with other treatment regimens.…”

“…13 Doravirine is a novel nonnucleoside reverse transcriptase inhibitor designed to overcome the limitations of other drugs within the same class. 14,15 Phase 2 and 3 trials in treatment-naïve HIV-1-infected adults have shown that doravirine in combination with other antiretroviral agents is noninferior in terms of efficacy, but also demonstrates a more favorable safety profile compared with other treatment regimens. [14][15][16][17] In the United States, doravirine is indicated for administration once daily at a dose of 100 mg, in combination with other antiretroviral agents, for the treatment of HIV-1 infection.…”