Doravirine (Pifeltro) is an anti-HIV drug that reduces the amount of virus in the body. It belongs to the class of drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Pifeltro contains 100mg of doravirine.
Doravirine is also available in a combination pill with lamivudine and tenofovir disoproxil fumarate (TDF), marketed as Delstrigo.
Doravirine was developed by Merck. It was approved in the European Union and United States in 2018 for treatment of HIV infection in combination with other antiretroviral drugs for people with no evidence of resistance to any drug in the NNRTI class.
Doravirine was approved based on findings from the phase 3 DRIVE-FORWARD and DRIVE-AHEAD clinical trials in previously untreated people.
The DRIVE-FORWARD study included 766 HIV-positive participants with no prior treatment experience. They were randomly assigned to receive once-daily doravirine or boosted darunavir (Prezista), each in combination with TDF/emtricitabine (Truvada) or abacavir/lamivudine (Kivexa).
After 48 weeks on treatment, 84% of people taking doravirine and 80% of those taking boosted darunavir had undetectable viral load (< 50 copies/ml), showing that doravirine was non-inferior. (Molina 2018)
DRIVE-AHEAD included 728 previously untreated participants. They were randomised to receive a fixed-dose co-formulation of doravirine, TDF and lamivudine – the same as the approved Delstrigo pill – or a single-tablet regimen containing efavirenz, TDF and emtricitabine (the drugs in Atripla).
After 48 weeks on treatment, 84% of people on the Delstrigo combo and 81% of those taking Atripla had undetectable viral load at 48 weeks, again showing that doravirine was non-inferior. Viral suppression rates were similar in the two treatment arms for people who started with either low or high (> 100,000 copies/ml) viral load at baseline. (Squires)
Doravirine was also investigated as a switch option for people with undetectable viral load. In the DRIVE-SHIFT study, 90% of participants randomised to switch to the fixed-dose combination of Delstrigo maintained an undetectable viral load compared to 94% of participants who continued treatment with a three-drug combination containing two NRTIs. (Kumar)
Doravirine is being investigated as part of a two-drug combination with islatravir, a first-in-class nucleoside reverse transcriptase translocation inhibitor developed by Merck. 96-week results of a phase 2 study of the combination show that people who switched from Delstrigo to doravirine and one of three doses of islatravir had a similar rate of viral suppression to people who continued taking Delstrigo. The two-drug regimen was well tolerated but vitamin D deficiency was three times more common in the islatravir arms. (Molina 2020)
Doravirine is taken once daily in combination with other drugs or as part of the fixed-dose combination Delstrigo. Doravirine can be taken with or without food.
Common side effects of doravirine include abnormal dreams, difficulty in sleeping, nightmare, depression, headache, dizziness, drowsiness, nausea, diarrhoea, abdominal pain, vomiting, rash, tiredness.
You should not take doravirine if you are currently taking the following medicines:
- carbamazepine, oxcarbazepine, phenobarbital, phenytoin (drugs used to treat epilepsy and seizures)
- rifampicin, rifapentine (treatment for tuberculosis)
- St John's wort (Hypericum perforatum) (a herbal remedy used for depression and anxiety)
- mitotane (a cancer treatment)
- enzalutamide (a treatment for prostate cancer)
- lumacaftor (treatment for cystic fibrosis).
Doravirine retains its activity against viruses with the most common NNRTI-associated resistance mutations (K103N, Y181C). (Feng)
Doravirine is not recommended for use by pregnant women due to lack of evidence on its effects during pregnancy.
Doravirine is not licensed for use in children.
Molina JM et al. 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. The Lancet HIV, 5: e211-e220, 2018.
Squires KE et al. Fixed-dose combination of doravirine/lamivudine/TDF is non-inferior to efavirenz/emtricitabine/TDF in treatment-naive adults with HIV-1 infection: week 48 results of the Phase 3 DRIVE-AHEAD study. 9th IAS Conference on HIV Science, Paris, abstract TUAB0104LB, July 23-26, 2017.
Kumar P et al. Switch to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) maintains virologic suppression through 48 weeks: results of the DRIVE-SHIFT trial. ID Week 2018, San Francisco, abstract LB-2, 3-7 October 2018.
Feng M et al. Doravirine suppresses common nonnucleoside reverse transcriptase inhibitor-associated mutants at clinically relevant concentrations. Antimicrobial Agents and Chemotherapy, 60: 2241-7, 2016.