Doravirine: Dose, Side Effects, and Key Studies
Learn about Doravirine (Pifeltro), a once-daily oral medication used as a non-nucleoside reverse transcriptase inhibitor (NNRTI) in the treatment of HIV. Discover its administration details, interactions, impact on renal and hepatic impairment, pregnancy considerations, common adverse effects, and key studies comparing it with other regimens like Darunavir.
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Doravirine (Pifeltro) Prepared by: Jehan Budak, MD David H. Spach, MD Last Updated: March 23, 2022 National HIVCurriculum www.hiv.uw.edu
Doravirine Basics Medication - Oral, once daily, non-nucleoside reverse transcriptase inhibitor (NNRTI) Administration - Few drug-drug interactions, can give with proton pump inhibitors, and no food requirements With Renal Impairment - No adjustment with mild, moderate, or severe renal impairment With Hepatic Impairment - No dose adjustment for Child-Pugh A or B; insufficient data for C Pregnancy - Inadequate data for use in pregnancy Common Adverse Effects ( 5%) - Nausea, dizziness, headache, fatigue, diarrhea, abdominal pain, abnormal dreams
Doravirine (Pifeltro) Doravirine 100 mg NNRTI Dose: 1 tablet once daily with or without food
Doravirine-Tenofovir DF-Lamivudine (Delstrigo) Doravirine is also available as a fixed dose combination Doravirine-Tenofovir DF-Lamivudine 100 mg 300 mg 300 mg NRTI NRTI NNRTI Dose: 1 tablet once daily with or without food
HIV Reverse Transcription NNRTI: Mechanism of Action Doravirine Polymerase Active Site NNRTI Binding Pocket HIV Reverse Transcriptase Illustration: Cognition Studio, Inc. and David H. Spach, MD
Doravirine + 2 NRTIs vs. Darunavir + Ritonavir + 2 NRTIs DRIVE FORWARD
Doravirine + 2 NRTIs vs. Darunavir + Ritonavir + 2 NRTIs DRIVE FORWARD: Design Design - Randomized, double-blind, phase 3 study comparing doravirine plus 2 NRTIs with darunavir, boosted with ritonavir, in combination with 2 NRTIs as initial antiretroviral therapy Doravirine + 2 NRTIs (n = 385) Inclusion Criteria - Antiretroviral-na ve adults - HIV RNA 1,000 copies/mL - No resistance to any study drug Darunavir + Ritonavir + 2 NRTIs (n = 384) Regimens (all once daily) - Doravirine (100 mg) + 2 NRTIs - Darunavir (800 mg) + Ritonavir (100 mg) + 2 NRTIs Source: Molina J-M, et al. Lancet HIV. 2018;5:e211-20.
Doravirine + 2 NRTIs vs. Darunavir + Ritonavir + 2 NRTIs DRIVE FORWARD: Results DRIVE FORWARD Baseline Characteristics DOR + 2 NRTIs (n = 383) DRV + RTV + 2 NRTIs (n = 383) Characteristic 34.8 35.7 Age (years), median 83.3 85.1 Male, % 73.1 73.1 White, % 432.6 411.9 CD4 count (cells/mm3), mean 4.4 4.4 HIV RNA, mean (log10) 24.3 24.5 HIV RNA >100,000 copies/mL, % 86.9 87.5 NRTI backbone TDF-FTC, % 13.1 12.5 NRTI backbone ABC-3TC, % Source: Molina J-M, et al. Lancet HIV. 2018;5:e211-20.
Doravirine + 2 NRTIs vs. Darunavir + Ritonavir + 2 NRTIs DRIVE FORWARD: 48 Week Results Week 48 Virologic Response (Intention-to-Treat Analysis) Doravirine + 2 NRTIs Darunavir + Ritonavir + 2 NRTIs 100 HIV RNA <50 copies/mL (%) 89.8 89.0 80 83.8 81.0 79.9 76.4 60 40 20 0 All >100,000 copies/mL 100,000 copies/mL Baseline HIV RNA Source: Molina J-M, et al. Lancet HIV. 2018;5:e211-20.
Doravirine + 2 NRTIs vs. Darunavir + Ritonavir + 2 NRTIs DRIVE FORWARD: Results DRIVE FORWARD: Treatment-Related Adverse Effects DOR + 2 NRTIs (n = 383) DRV + RTV + 2 NRTIs (n = 383) Adverse Effect Any adverse drug-related event % 31 32 Discontinued due to drug-related AE, % 1 2 Upper abdominal pain, % 2 1 Diarrhea, % 5 13 Nausea, % 7 8 Headache, % 6 3 Dizziness, % 3 2 Fatigue, % 5 2 Rash, % 2 3 Neuropsychiatric, % 6 5 Source: Molina J-M, et al. Lancet HIV. 2018;5:e211-20.
Doravirine + 2 NRTIs vs. Darunavir + Ritonavir + 2 NRTIs DRIVE FORWARD: Results Change in Baseline Fasting Lipids at Week 48 Doravirine + 2 NRTIs Darunavir + Ritonavir + 2 NRTIs 30 Change from Baseline, mg/dL 22.0 17.9 20 9.9 10 4.2 3.9 0 -1.4 -3.1 -4.5 -10 Cholesterol LDL Cholesterol HDL Cholesterol Triglycerides Source: Molina J-M, et al. Lancet HIV. 2018;5:e211-20.
Doravirine + 2 NRTIs vs. Darunavir + Ritonavir + 2 NRTIs DRIVE FORWARD: Conslusion Interpretation: In treatment-naive adults with HIV-1 infection, doravirine combined with two NRTIs might offer a valuable treatment option for adults with previously untreated HIV-1 infection. Source: Molina J-M, et al. Lancet HIV. 2018;5:e211-20.
Acknowledgments The National HIV Curriculum is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award totaling $1,021,448 with 0% financed with non-governmental sources. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by HRSA, HHS, or the U.S. Government. For more information, please visit HRSA.gov. This project is led by the University of Washington s Infectious Diseases Education and Assessment (IDEA) Program.
