doravirine/lamivudine/tenofovir DF (DOR/3TC/TDF)
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). Approved only for adults at this time.
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; Delstrigo is not recommended in people with estimated creatinine clearance less than 50 mL/min. 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 the individual drugs contained in Delstrigo: Pifeltro, Viread, and Epivir.
• See package insert for more complete information on potential side effects and interactions.
The most common adverse reactions observed with Delstrigo in clinical trials (in more than at least 5% of people taking it) were dizziness (7%), nausea (5%), abnormal dreams (5%), and increased lipase (5%). In one study (DRIVE-AHEAD), an in-depth analysis was conducted of the incidence of neuropsychiatric adverse events associated with Delstrigo compared to Atripla. Neuropsychiatric events, such as depression, sleep disturbances, dizziness, etc., are another common side effect of the NNRTI class. The proportion of subjects who reported one or more neuropsychiatric adverse events overall was 24% for the Delstrigo group compared to 57% for the Atripla group. The neuropsychiatric adverse events associated with depression and suicide/self-injury were reported in 4% of the Delstrigo group compared to 7% of the Atripla group. Overall, sleep disturbances (e.g., abnormal dreams, insomnia, nightmares, etc.) were associated with 12% of people in the Delstrigo group compared to 26% of people in the Atripla group. Dizziness was associated with 9% in the Delstrigo group compared to 37% of the Atripla group. Altered sensorium (e.g., lethargy, drowsiness, etc.) was associated with 4% of people in the Delstrigo group compared to 8% of people in the Atripla group. The doravirine component of Delstrigo did not appear to negatively affect cholesterol in studied populations. Decreases in bone mineral density (BMD) have been observed in patients on TDF-containing regimens. BMD monitoring should be considered in people who have a history of bone fracture due to bone disease or are at risk for osteopenia or osteoporosis. TDF may cause kidney toxicities. Creatinine clearance (CrCl) should be assessed before initiating treatment. In addition to CrCl, glucose and protein in the urine and serum phosphorus should be monitored more often in patients at risk for kidney problems. Tell your provider about any pain in extremities, persistent or worsening bone pain and fractures, with or without muscular pain or weakness, as well as any concerning changes in urinary habits, as these could be signs of kidney problems. If you have HIV and HBV, guidelines recommend treatment for both viruses. Delstrigo can be used to treat HIV and HBV simultaneously. If you are co-infected with HBV and HIV, you should not stop Delstrigo without medical supervision because it can cause your HBV to flare and cause you to experience signs and symptoms of acute hepatitis. HBV should be closely monitored by your provider.
Potential Drug Interactions
New interactions continue to be discovered after drug approval (doravirine is the new drug). Do not take with Epivir-HBV, Hepsera, or Vemlidy (TAF), all three used for hepatitis B. When using with the antibiotic drug rifabutin (used for TB and to prevent MAC in AIDS patients), increase the doravirine dose by adding a Pifeltro tablet approximately 12 hours later. The following medications may lower the blood levels of doravirine, and therefore may decrease its effectiveness, and should not be used with Delstrigo: the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent (cancer drug) mitotane; and the herbal St. John’s wort. Avoid use of sorbitol-containing medicines with lamivudine; there are many, such as acetaminophen liquid (Tylenol liquid and others). Epclusa and Harvoni each increase the concentration of TDF; monitor for adverse reactions. Not intended to be taken with other HIV medications, unless prescribed that way. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions which are not listed here.
Stand-alone versions of doravirine (Pifeltro) and lamivudine/tenofovir DF (Cimduo) were also approved; see those pages. Unfortunately, Delstrigo contains an older version of tenofovir, TDF. A safer version, TAF, is available and used in some STRs. TDF is still an effective and quite tolerable medication, but TAF has less toxicity to the kidneys and bones. Doravirine has not been directly compared to integrase inhibitor-based regimens in clinical trials yet. There is no data on the safety of Delstrigo use in pregnancy.
In the DRIVE-FORWARD study comparing doravirine to darunavir, results for the treatment-naïve individuals in the study were 80% (darunavir group) and 84% (doravirine group) undetectable (less than 50 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. See more data online. Delstrigo now has a switch indication, so that people with undetectable viral load on a stable HIV treatment can switch to it if they have no drug resistance to any of the medications in Delstrigo and no history of treatment failure.
Dr. David Hardy says:
Delstrigo was approved in August 2018 and is the twelfth STR and first “quasi-generic” STR approved by the FDA. The term “quasi-generic” means that two of the components of Delstrigo, tenofovir DF and lamivudine, are from a generic, non-branded manufacturer, and the Pifeltro (doravirine) is the branded drug made by the manufacturer, Merck. Doravirine is considered to be a “second generation” NNRTI due to its enhanced resistance profile compared to Sustiva and Viramune and similar to other NNRTIs such as Intelence and Edurant. In fact, lab studies predict that it may be effective after a first generation NNRTI has failed and caused HIV resistance mutations or in PLWH with transmitted NNRTI resistance. To test this laboratory finding, a clinical trial called the DRIVE BEYOND study, which enrolled ART treatment-naïve PLWH with transmitted HIV resistance (K103N, Y181C, or G190A mutations), completed its initial follow-up in late 2018. We look forward to hearing the outcome of this study in 2019. Data from two large clinical trials of treatment-naïve PLWH comparing Delstrigo to Sustiva (DRIVE AHEAD study) and to Prezista/Norvir (DRIVE FORWARD study) have shown that Delstrigo has similar anti-HIV potency as those two known potent medications with less treatment-limiting side effects and less cholesterol-elevating effects. Of note and what will hopefully be a growing trend which other newly approved STRs will follow, the 30-day wholesale acquisition cost (WAC) of Delstrigo is $2,100, compared to $2,950 for Biktarvy, $3,500 for Symtuza, $2,800 for Triumeq, $3,000 for Genvoya and Stribild, and $1,630 for Symfi and Symfi Lo.
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.
Activist Moisés Agosto-Rosario says:
Delstrigo was approved for patients who have not been treated with antiretrovirals before. In general, it is safe and well tolerated. If you have hepatitis B (HBV) and are taking Delstrigo, do not stop taking it and make sure you never run out of it. This is not only because you want to maintain HIV viral suppression, which is a good reason, but, if you stop the medicine, the HBV infection suddenly returns in a worse way than before. If for some reason you need to stop taking Delstrigo, your doctor will need to monitor your HBV infection by doing regular blood tests for a few months.