doravirine/tenofovir DF/lamivudine (DOR/TDF/3TC)
Standard DoseOne tablet once daily without regard to food. Tablet contains 100 mg of the NNRTI doravirine plus 300 mg lamivudine and 300 mg tenofovir DF (TDF).
Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Dose cannot be adjusted for people with kidney problems; DOR/TDF/3TC should not be used in people with moderate or severe kidney impairment or severe liver impairment.
ManufacturerMerck and Co.
Potential Side Effects and Toxicity
See package insert. An analysis at 48 weeks showed that the most common drug-related side effects that occurred in more than 5% of participants taking either 100 mg of doravirine or 600 mg of efavirenz (brand name Sustiva) were diarrhea, nausea, dizziness, headache, abnormal dreams, insomnia, nightmares, and sleep disorder. All of the above side effects, except nausea and insomnia, occurred in a greater number of participants in the efavirenz group than in the doravirine group. Three participants taking doravirine and six participants taking efavirenz stopped treatment because of a side effect. In one study, side effects observed in 10% or more of 383 patients taking this doravirine regimen included nausea (11%), neuropsychiatric symptoms (such as depression, abnormal dreams, insomnia, and dizziness) (11%), diarrhea (14%), and headache (14%). In Phase 2b study, neuropsychiatric side effects with doravirine were significantly less than were seen with participants receiving efavirenz. In the Phase III study comparing doravirine to darunavir (brand name Prezista) plus ritonavir, an analysis at 48 weeks showed that participants in both groups experienced side effects related to the brain (including dizziness, depression, insomnia, and abnormal dreams), but no one dropped out of the study because of these side effects. Doravirine lowered cholesterol levels while darunavir + ritonavir increased them. Headache, diarrhea, and cold symptoms were the most frequently reported side effects in the group taking the fixed-dose tablet containing doravirine. Prior to initiation, people should be tested for hepatitis B (HBV) infection. Severe exacerbations of hepatitis B have been reported in people who are co-infected with hepatitis B and have discontinued the lamivudine and/or tenofovir components. Monitor liver enzymes closely in people co-infected with hepatitis B and, if appropriate, initiation of anti-hepatitis B therapy may be warranted.
Potential Drug Interactions
See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not. Do not take with any other HIV antiretroviral medication unless specifically instructed to do so by expert consultation. Therefore, do not take with the following HIV medications, since these are already in this drug or they have medication from similar drugs: Atripla, Biktarvy, Combivir, Complera, Descovy, Epivir, Emtriva, Epzicom, Genvoya, Juluca, Odefsey, Pifeltro, Stribild, Triumeq, Trizivir, Truvada, or Viread; also Epivir-HBV, Hepsera, or Vemlidy (TAF), all three used for hepatitis B.
Received FDA approval this year. A stand-alone version of doravirine (Pifeltro) was also approved; see Pifeltro page. Doravirine was found to be non-inferior to boosted darunavir (Prezista) at 48 weeks in the DRIVE-FORWARD study. Darunavir is one of two protease inhibitor medications recommended for first-time use in certain clinical situations by U.S. HIV treatment guidelines. Doravirine has not yet been compared to an integrase inhibitor (INSTI), almost all of which are DHHS recommended for most people taking HIV medication for the first time (one INSTI STR was approved as this issue went to press, and has not yet received a recommendation).
In the study mentioned above comparing doravirine to darunavir (DRIVE-FORWARD), the treatment-naïve individuals in the study were 80% (darunavir group) and 84% (doravirine group) undetectable (less than 50 copies viral load). That’s a lower success rate than is expected in HIV treatment today, but was thought to be affected by the number of people who quickly dropped out of the study when they saw how many pills they had to take. Those drop-outs were counted as virologic failures. Only 1 of 364 doravirine-treated patients developed drug resistance, a low number for an NNRTI; there was no resistance noted in the boosted darunavir group.
The doravirine STR is being studied in treatment-naïve individuals (first time on HIV therapy) who have virus that doesn’t respond well to other NNRTIs (the DRIVE BEYOND study). It is also being studied in people with undetectable viral loads on their current treatment who are switched to the doravirine STR (the Phase 3 DRIVE-SHIFT study).
See package insert for more complete information.
Dr. David Hardy says:
Doravirine is considered a “second generation” NNRTI because of its enhanced resistance profile compared to Sustiva and other older “first generation” NNRTIs. In fact, lab studies predict that it may be effective after a first generation NNRTI has failed and left HIV resistance mutations. To date, data from two large clinical trials comparing doravirine to Sustiva and to Prezista/Norvir have shown that doravirine has similar anti-HIV potency as those two known potent medications and with fewer side effects. Doravirine is also being dveloped as an STR, and as a stand-alone pill. The FDA has set a target action date of Oct. 23, 2018, for both applications for doravirine and doravirine/Viread/Epivir under the Prescription Drug User Fee Act (PDUFA).
Activist Moisés Agosto-Rosario says:
This new STR contains the investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) doravirine (DOR). This new drug is effective against NNRTI drug-resistant mutations. Individuals with resistance to other NNRTIs will benefit from regimens containing DOR. The potency of doravirine is comparable to efavirenz and boosted darunavir, when used in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-naïve individuals. Brain and central nervous system side effects are less common in individuals taking doravirine compared to those taking efavirenz. Doravirine has not yet been approved by the FDA. It will be available as a stand-alone NNRTI. This co-formulation with TDF and 3TC promises to be a safe and potent NNRTI-based STR.