Doravirine, Lamivudine, and Tenofovir Disoproxil (Monograph)
Drug class: HIV Nonnucleoside Reverse Transcriptase Inhibitors
Chemical name: 3-chloro-5-[1-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methyl]-2-oxo-4-(trifluoromethyl)pyridin-3-yl]oxybenzonitrile
Molecular formula: C17H11ClF3N5O3C8H11N3O3SC9H14N5O4P • H2O
CAS number: 1338225-97-0
Warning
- HBV Infection
-
Severe, acute exacerbations of HBV infection reported following discontinuance of lamivudine or tenofovir DF in patients coinfected with HIV and HBV.1 219 221 Monitor hepatic function closely with both clinical and laboratory follow-up for at least several months after doravirine/lamivudine/tenofovir DF is discontinued in patients coinfected with HIV and HBV.1 If appropriate, initiation of HBV treatment may be warranted.1 (See HIV-infected Individuals Coinfected with HBV under Cautions.)
Introduction
Antiretroviral; fixed combination of doravirine, lamivudine, and tenofovir disoproxil fumarate (doravirine/lamivudine/tenofovir DF).1 Doravirine is an HIV nonnucleoside reverse transcriptase inhibitor (NNRTI), lamivudine is an HIV nucleoside reverse transcriptase inhibitor (NRTI), and tenofovir DF is an HIV nucleotide reverse transcriptase inhibitor classified as an NRTI.1
Uses for Doravirine, Lamivudine, and Tenofovir Disoproxil
Treatment of HIV Infection
Treatment of HIV-1 infection in antiretroviral-naive (have not previously received antiretroviral therapy) or antiretroviral-experienced (previously treated) adults.1 2 3 30 200
Fixed combination of doravirine/lamivudine/tenofovir DF used alone as a complete regimen for treatment of HIV-1 infection;1 200 use with other antiretrovirals not recommended.1
For initial treatment in antiretroviral-naive adults, experts state that doravirine/lamivudine/tenofovir DF is a recommended NNRTI-based regimen in certain clinical situations.200
For antiretroviral-experienced adults, manufacturer states that doravirine/lamivudine/tenofovir DF can be used to replace the current antiretroviral regimen in those with plasma HIV-1 RNA levels <50 copies/mL on a stable antiretroviral regimen who have no history of treatment failure and are infected with HIV-1 with no known substitutions associated with resistance to doravirine, lamivudine, or tenofovir DF.1
Most appropriate antiretroviral regimen cannot be defined for every clinical scenario; select regimen based on information regarding antiretroviral potency, potential rate of resistance development, known toxicities, potential for pharmacokinetic interactions, and patient's virologic, immunologic, and clinical characteristics.200 201 202 Guidelines for the management of HIV infection, including specific recommendations for initial treatment in antiretroviral-naive patients and recommendations for changing antiretroviral regimens, are available at [Web].200 201 202
Related/similar drugs
Biktarvy, Descovy, Truvada, Atripla, Epzicom, Stribild, Complera
Doravirine, Lamivudine, and Tenofovir Disoproxil Dosage and Administration
General
-
Determine Scr, estimated Clcr, urine glucose, and urine protein prior to initiation of doravirine/lamivudine/tenofovir DF and routinely monitor during treatment in all patients as clinically appropriate.1 Also determine serum phosphorus in patients with chronic kidney disease.1 (See Renal Impairment under Cautions.)
-
Test for HBV infection prior to initiation.1 (See HIV-infected Individuals Coinfected with HBV under Cautions.)
Administration
Oral Administration
Administer orally once daily without regard to food.1
Doravirine/lamivudine/tenofovir DF is used alone as a complete antiretroviral regimen.1
Dosage
Each fixed-combination tablet of doravirine/lamivudine/tenofovir DF contains doravirine 100 mg, lamivudine 300 mg, and tenofovir DF 300 mg.1
Adults
Treatment of HIV Infection
Antiretroviral-naive or Antiretroviral-experienced Adults
Oral1 tablet of doravirine/lamivudine/tenofovir DF (doravirine 100 mg, lamivudine 300 mg, tenofovir DF 300 mg) once daily.1
Antiretroviral-naive or Antiretroviral-experienced Adults Receiving Rifabutin
Oral1 tablet of doravirine/lamivudine/tenofovir DF (doravirine 100 mg, lamivudine 300 mg, tenofovir DF 300 mg) once daily and one 100-mg tablet of single-entity doravirine once daily given approximately 12 hours after the fixed-combination tablet.1 (See Specific Drugs under Interactions.)
Special Populations
Hepatic Impairment
Mild or moderate hepatic impairment (Child-Pugh class A or B): Dosage adjustments not needed.1
Severe hepatic impairment (Child-Pugh class C): Not studied.1 (See Hepatic Impairment under Cautions.)
Renal Impairment
Estimated Clcr <50 mL/minute: Not recommended.1 (See Renal Impairment under Cautions.)
Geriatric Patients
No specific dosage recommendations;1 use with caution because of possible age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.1 (See Geriatric Use under Cautions.)
Cautions for Doravirine, Lamivudine, and Tenofovir Disoproxil
Contraindications
-
Concomitant use with potent CYP3A inducers (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, St. John’s wort [Hypericum perforatum]).1 (See Specific Drugs under Interactions.)
-
History of hypersensitivity reaction to lamivudine.1
Warnings/Precautions
Warnings
HIV-infected Individuals Coinfected with HBV
Test all HIV-infected patients for presence of HBV before initiating antiretroviral therapy.1 200
In HIV-infected patients with HBV coinfection, severe acute exacerbations of HBV, including liver decompensation and liver failure, reported following discontinuance of lamivudine or tenofovir DF (components of doravirine/lamivudine/tenofovir DF).1 219 221 Such reactions could occur following discontinuance of doravirine/lamivudine/tenofovir DF.1
Closely monitor hepatic function (using both clinical and laboratory follow-up) for at least several months after doravirine/lamivudine/tenofovir DF is discontinued in patients coinfected with HIV and HBV.1 If appropriate, initiation of HBV treatment may be warranted, especially in patients with advanced liver disease or cirrhosis.1
Other Warnings and Precautions
Renal Toxicity
Renal impairment, including acute renal failure and Fanconi syndrome (renal tubular injury with hypophosphatemia), reported with tenofovir DF (a component of doravirine/lamivudine/tenofovir DF).1 221
Determine Scr, estimated Clcr, urine glucose, and urine protein prior to initiation of doravirine/lamivudine/tenofovir DF and routinely monitor as clinically appropriate during treatment in all patients.1 Also determine serum phosphorus in those with chronic kidney disease.1 (See Renal Impairment under Cautions.)
Discontinue doravirine/lamivudine/tenofovir DF if clinically important decreases in renal function or evidence of Fanconi syndrome occurs or if estimated Clcr decreases to <50 mL/minute.1
Because persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy, promptly evaluate renal function in patients at risk for renal dysfunction who present with such symptoms.1 (See Bone Effects under Cautions.)
Avoid doravirine/lamivudine/tenofovir DF in patients who are receiving or have recently received a nephrotoxic drug (e.g., high-dose or multiple NSAIAs).1 Acute renal failure reported after initiation of high-dose or multiple NSAIAs in HIV-infected patients at risk for renal dysfunction who appeared stable while receiving tenofovir DF; hospitalization and renal replacement therapy required in some patients.1 Consider alternatives to NSAIAs in patients at risk for renal dysfunction.1
Bone Effects
Decreases in bone mineral density (BMD) from baseline at lumbar spine and hip, increases in several biochemical markers of bone metabolism, and increased serum parathyroid hormone and 1,25 vitamin D levels reported in patients receiving tenofovir DF (a component of doravirine/lamivudine/tenofovir DF).1 221 Effects of tenofovir-associated changes in BMD on long-term bone health and future fracture risk unknown.1 221
Osteomalacia associated with proximal renal tubulopathy, which may contribute to fractures, reported in patients receiving tenofovir DF.1 221 Arthralgia and muscle pain or weakness also reported in cases of proximal renal tubulopathy.1 Consider hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving preparations containing tenofovir DF.1
Consider BMD monitoring in adults with history of pathologic bone fracture or other risk factors for osteoporosis or bone loss.1 Effect of calcium and vitamin D supplementation not studied, but may be beneficial for all patients.1 If bone abnormalities suspected, obtain appropriate consultation.1
Interactions
Concomitant use with certain drugs may result in known or potentially clinically important drug interactions, some of which may lead to loss of therapeutic effect of the antiretrovirals and possible development of resistance or may increase plasma concentrations of the antiretroviral agents and/or concomitant drugs leading to clinically important adverse reactions.1
Consider potential for drug interactions prior to and during doravirine/lamivudine/tenofovir DF therapy;1 review concomitant drugs during doravirine/lamivudine/tenofovir DF therapy and monitor for adverse effects.1 (See Interactions.)
Immune Reconstitution Syndrome
Immune reconstitution syndrome reported in HIV-infected patients receiving multiple-drug antiretroviral therapy.1 During the initial phase of treatment, HIV-infected patients whose immune systems respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii], tuberculosis);1 such responses may necessitate further evaluation and treatment.1
Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) also reported in the setting of immune reconstitution; however, time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1
Use of Fixed Combinations
Consider cautions, precautions, contraindications, and interactions associated with each component of doravirine/lamivudine/tenofovir DF.1 219 221 Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug in the fixed combination.1 219 221
Doravirine/lamivudine/tenofovir DF is used alone as a complete regimen;1 use in conjunction with other antiretrovirals not recommended.1
Specific Populations
Pregnancy
Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].1 202
Doravirine/lamivudine/tenofovir DF: Insufficient data in pregnant women to assess the risk of birth defects and miscarriage.1
Doravirine: Human data not available to establish whether or not doravirine poses a risk to pregnancy outcomes.1 202 255 In animal reproduction studies, no adverse developmental effects observed in rabbits or rats at exposures 8 or 9 times higher, respectively, than human exposures at recommended human dosage.255 In pregnant rabbits and rats, doravirine crossed the placenta resulting in fetal plasma concentrations up to 40 and 52%, respectively, of maternal concentrations observed on gestation day 20.1 202 255
Lamivudine: Available human data show no difference in the overall risk of major birth defects.1 202 In pregnant rabbits, oral administration during organogenesis resulted in embryolethality at systemic exposures similar to the recommended clinical dose;1 202 no adverse development effects observed in rats and rabbits with oral administration during organogenesis at peak plasma concentrations approximately 35 times higher than human exposure at the recommended clinical dose.1 202
Tenofovir DF: Available human data show no difference in the overall risk of major birth defects.1 202 No adverse developmental effects observed in pregnant rats and rabbits at doses up to 14 and 19 times higher, respectively, than recommended human dosage.1
Lactation
Doravirine: Not known whether distributed into human milk.1 Distributed into milk of lactating rats (milk concentrations approximately 1.5 times higher than maternal plasma concentrations at 2 hours after a dose on lactation day 14).1
Lamivudine and tenofovir DF: Distributed into human milk.1 202
Doravirine/lamivudine/tenofovir DF: Not known whether the fixed combination or individual drug components affect human milk production or affect the breast-fed infant.1
Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1 202
Pediatric Use
Safety and efficacy not established in pediatric patients <18 years of age.1
Geriatric Use
Experience in patients ≥65 years of age insufficient to determine whether they respond differently than younger adults.1
Use with caution in geriatric patients because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.1
Hepatic Impairment
Doravirine: No clinically important differences in doravirine pharmacokinetics in patients with moderate hepatic impairment (Child-Pugh class B).1 Not studied in those with severe hepatic impairment (Child-Pugh class C).1
Lamivudine: Pharmacokinetics not substantially affected by diminishing hepatic function.1 Safety and efficacy not established in patients with decompensated liver disease.1
Tenofovir: Pharmacokinetics not substantially affected by any degree of hepatic impairment.1
Renal Impairment
Not recommended in patients with estimated Clcr <50 mL/minute because dosage of lamivudine and tenofovir DF (components of doravirine/lamivudine/tenofovir DF) cannot be adjusted for renal impairment.1
Common Adverse Effects
Dizziness, nausea, abnormal dreams.1
Drug Interactions
The following drug interactions are based on studies using the individual components of doravirine/lamivudine/tenofovir DF.1 Consider interactions associated with each drug in the fixed combination.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Doravirine: Primarily metabolized by CYP3A.1 16 In vitro, does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4; not likely to induce CYP1A2, 2B6, or 3A4.1 16 Concomitant use of doravirine and CYP3A inducers may decrease doravirine plasma concentrations and may reduce efficacy of doravirine.1 Concomitant use of doravirine/lamivudine/tenofovir DF with CYP3A inhibitors may increase doravirine plasma concentrations.1 Not likely to have a clinically important effect on the exposure of drugs metabolized by CYP isoenzymes.1
Lamivudine: Not substantially metabolized by CYP isoenzymes;1 does not inhibit or induce CYP isoenzymes.1 Clinically important CYP-mediated drug interactions unlikely.1
Tenofovir DF: Not a substrate of CYP isoenzymes.1 In vitro, does not inhibit CYP isoenzymes 3A4, 2D6, 2C9, or 2E1; may have a slight inhibitory effect on CYP1A.1 Pharmacokinetic interactions with inhibitors or substrates of CYP isoenzymes unlikely.1
Drugs Affecting or Metabolized by UGT
Doravirine: In vitro, does not inhibit UGT1A1.1 16
Drugs Affecting or Affected by Other Transporters
Doravirine: Based on in vitro studies, not likely to inhibit P-glycoprotein (P-gp) transport system, organic anion transport polypeptide (OATP) 1B1, OATP1B3, bile salt export pump (BSEP), organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 2, multidrug and toxin extrusion transporter (MATE) 1, or MATE2K.1 7 16 Not a substrate of breast cancer resistance protein (BCRP); unlikely to be a substrate of OATP1B1 or 1B3.16
Lamivudine: Primarily eliminated in urine by active organic cationic secretion.219 Potential pharmacokinetic interactions with drugs that are primarily eliminated by active renal secretion via organic cationic transport.219
Drugs Affecting Renal Function
Drugs that reduce renal function or compete for active tubular secretion: Potential increased concentrations of lamivudine, tenofovir, and/or concomitant drug.1
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Adefovir dipivoxil |
Tenofovir DF: Data not available200 |
Tenofovir DF: Do not use concomitantly with adefovir dipivoxil200 |
α1-Adrenergic blocking agents |
Alfuzosin, doxazosin, silodosin, tamsulosin: No effect on α1-adrenergic blocking agent concentrations expected if used with doravirine200 |
Dosage adjustments not needed if used with doravirine200 |
Antacids |
Antacid containing aluminum hydroxide, magnesium hydroxide, and simethicone: No clinically important effect on doravirine concentrations1 11 |
Dosage adjustments not needed if used with doravirine200 |
Anticoagulants |
Apixaban, betrixaban, dabigatran, edoxaban, rivaroxaban: No effect on anticoagulant concentrations expected if used with doravirine200 Warfarin: No effect on warfarin concentrations expected if used with doravirine200 |
Apixaban, betrixaban, dabigatran, edoxaban, rivaroxaban: Experts state dosage adjustments not needed if used with doravirine200 Warfarin: Dosage adjustments not needed if used with doravirine200 |
Anticonvulsants |
Carbamazepine, oxcarbazepine, phenobarbital, phenytoin: Decreased doravirine concentrations expected; possible decreased doravirine efficacy1 200 Eslicarbazepine: Possible decreased doravirine concentrations200 Ethosuximide, lacosamide, lamotrigine, tiagabine, zonisamide: No effect on anticonvulsant concentrations expected if used with doravirine200 |
Carbamazepine, oxcarbazepine, phenobarbital, phenytoin: Concomitant use contraindicated;1 200 do not initiate doravirine/lamivudine/tenofovir DF until ≥4 weeks after anticonvulsant discontinued;1 experts state consider alternative anticonvulsant200 Eslicarbazepine: If used concomitantly, experts state monitor virologic outcomes and consider doravirine plasma concentration monitoring;200 alternatively, consider different antiretroviral or anticonvulsant200 Ethosuximide, lacosamide, lamotrigine, tiagabine, zonisamide: Dosage adjustments not needed if used with doravirine200 |
Antidiabetic agents |
Canagliflozin, dapagliflozin, empagliflozin: No effect on antidiabetic agent concentrations expected if used with doravirine200 Linagliptin, saxagliptin, sitagliptin: No effect on antidiabetic agent concentrations expected if used with doravirine200 Metformin: No clinically important effect on metformin concentrations when used with doravirine;1 9 possible decreased doravirine concentrations and AUC200 |
Canagliflozin, dapagliflozin, empagliflozin: Dosage adjustments not needed if used with doravirine200 Linagliptin, saxagliptin, sitagliptin: Dosage adjustments not needed if used with doravirine200 Metformin: Dosage adjustments not needed if used with doravirine9 200 |
Antifungals, azoles |
Fluconazole, isavuconazonium sulfate [prodrug of isavuconazole], itraconazole, voriconazole: Possible increased doravirine concentrations200 Ketoconazole: Increased doravirine exposures and peak plasma concentrations;1 15 not considered clinically important1 15 Posaconazole: Possible increased doravirine concentrations200 |
Fluconazole, isavuconazonium sulfate, itraconazole, voriconazole: Dosage adjustments not needed if used with doravirine200 Posaconazole: Experts state monitor for doravirine-associated toxicities200 |
Antimalarial and antiprotozoal agents |
Atovaquone: Data not available regarding use with doravirine200 Fixed combination of artemether and lumefantrine (artemether/lumefantrine): No effect on antimalarial agent concentrations expected if used with doravirine200 Fixed combination of atovaquone and proguanil (atovaquone/proguanil): Data not available regarding use with doravirine200 |
Atovaquone: Experts recommend monitoring for antiprotozoal efficacy if used with doravirine200 Artemether/lumefantrine: Dosage adjustments not needed if used with doravirine200 Atovaquone/proguanil: Experts recommend monitoring for antimalarial efficacy if used with doravirine200 |
Antimycobacterials (bedaquiline, rifamycins) |
Bedaquiline: No effect on bedaquiline concentrations expected if used with doravirine200 Rifabutin: Decreased doravirine AUC and trough plasma concentrations; peak plasma concentrations not affected1 13 Rifampin: Decreased doravirine AUC, peak plasma concentrations, and trough plasma concentrations; possible decreased doravirine efficacy1 8 200 Rifapentine: Decreased doravirine concentrations expected; possible decreased efficacy of doravirine1 200 |
Bedaquiline: Dosage adjustments not needed if used with doravirine200 Rifabutin: Increase doravirine dosage by using doravirine/lamivudine/tenofovir DF in conjunction with single-entity doravirine (see Antiretroviral-naive or Antiretroviral-experienced Adults Receiving Rifabutin under Dosage and Administration)1 Rifampin, rifapentine: Concomitant use contraindicated;1 200 do not initiate doravirine/lamivudine/tenofovir DF until ≥4 weeks after rifampin or rifapentine discontinued1 |
Antiplatelet agents |
Ticagrelor, vorapaxar: No effect on antiplatelet agent concentrations expected if used with doravirine200 |
Ticagrelor, vorapaxar: Dosage adjustments not needed if used with doravirine200 |
Antipsychotic agents |
Aripiprazole, brexpiprazole, cariprazine, lurasidone, pimavanserin, pimozide, quetiapine: No effect on antipsychotic agent concentrations expected200 |
Aripiprazole, brexpiprazole, cariprazine, lurasidone, pimavanserin, pimozide, quetiapine: Dosage adjustments not needed if used with doravirine200 |
Benzodiazepines |
Alprazolam, diazepam, lorazepam, triazolam: No effect on benzodiazepine concentrations expected if used with doravirine200 Midazolam: No clinically important pharmacokinetic interactions with doravirine1 |
Alprazolam, diazepam, lorazepam, midazolam, triazolam: Dosage adjustments not needed if used with doravirine200 |
Buprenorphine |
Doravirine: No effect on buprenorphine concentrations expected if used with doravirine200 Lamivudine or tenofovir DF: No clinically important pharmacokinetic interactions200 |
Doravirine: Dosage adjustments not needed200 Lamivudine or tenofovir DF: Dosage adjustments not needed200 |
Bupropion |
No effect on bupropion concentrations expected if used with doravirine200 |
Dosage adjustments not needed if used with doravirine200 |
Calcium-channel blocking agents |
Dihydropyridine calcium-channel blocking agents: No effect on concentrations of these calcium-channel blocking agents expected if used with doravirine200 Diltiazem, verapamil: Possible increased doravirine concentrations;200 no effect on diltiazem or verapamil concentrations expected if used with doravirine200 |
Dihydropyridine calcium-channel blocking agents, diltiazem, verapamil: Dosage adjustments not needed if used with doravirine200 |
Co-trimoxazole |
Lamivudine: Increased lamivudine AUC and decreased lamivudine oral clearance; no effect on pharmacokinetics of trimethoprim or sulfamethoxazole1 219 |
|
Dasabuvir |
Dasabuvir used with the fixed combination of ombitasvir, paritaprevir, and ritonavir (ombitasvir/paritaprevir/ritonavir): Possible increased doravirine concentrations200 |
Dasabuvir used with ombitasvir/paritaprevir/ritonavir: Dosage adjustments not needed if used with doravirine200 |
Dexamethasone |
Doravirine: Possible decreased doravirine concentrations200 |
Doravirine: Experts state consider an alternative corticosteroid for long-term use;200 if used concomitantly, monitor virologic response200 |
Dutasteride |
Doravirine: Pharmacokinetic interactions not expected10 |
|
Elbasvir and grazoprevir |
Elbasvir and grazoprevir: No clinically important pharmacokinetic interactions with doravirine1 14 200 |
Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): Dosage adjustments not needed if used with doravirine14 200 |
Entecavir |
Tenofovir DF: No clinically important pharmacokinetic interactions1 221 |
|
Enzalutamide |
Decreased doravirine concentrations expected; possible decreased doravirine efficacy1 200 |
Concomitant use contraindicated;1 200 do not initiate doravirine/lamivudine/tenofovir DF until ≥4 weeks after enzalutamide discontinued1 |
Estrogens and progestins |
Contraceptives containing ethinyl estradiol or levonorgestrel (oral): No effect on ethinyl estradiol or levonorgestrel concentrations expected if used with doravirine or tenofovir DF1 15 200 Contraceptives containing etonogestrel or levonorgestrel (transdermal systems) and contraceptives containing ethinyl estradiol and etonogestrel or segesterone (vaginal rings): No effect on concentrations of these hormones expected if used with doravirine200 Medroxyprogesterone: No effect on concentrations of the hormone expected if used with doravirine200 |
Contraceptives containing ethinyl estradiol and levonorgestrel (oral): Dosage adjustments not needed if used with doravirine15 200 Contraceptives containing etonogestrel or levonorgestrel (transdermal systems) and contraceptives containing ethinyl estradiol and etonogestrel or segesterone (vaginal rings): Dosage adjustments not needed if used with doravirine200 Medroxyprogesterone: Dosage adjustments not needed if used with doravirine200 |
Ganciclovir and valganciclovir |
Tenofovir DF: Concomitant use with ganciclovir or valganciclovir may result in increased tenofovir and/or ganciclovir concentrations1 221 |
Tenofovir DF: Monitor for dose-related toxicities of tenofovir and/or ganciclovir200 |
Glecaprevir and pibrentasvir |
Fixed combination of glecaprevir and pibrentasvir (glecaprevir/pibrentasvir): Possible increased doravirine concentrations;200 no clinically important effect on tenofovir concentrations200 |
Glecaprevir/pibrentasvir: Dosage adjustments not needed if used with doravirine or tenofovir DF200 |
Histamine H2-receptor antagonists |
No effect on doravirine concentrations expected200 |
Dosage adjustments not needed if used with doravirine200 |
HMG-CoA reductase inhibitors (statins) |
Atorvastatin: No clinically important effect on atorvastatin concentrations when used with doravirine1 7 200 Fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin: No effect on statin concentrations expected if used with doravirine200 |
Atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin: Dosage adjustments not needed if used with doravirine200 |
Immunosuppressive agents |
Cyclosporine: Possible increased doravirine concentrations; no effect on cyclosporine concentrations expected if used with doravirine200 Everolimus, sirolimus, tacrolimus: No effect on immunosuppressive agent concentrations expected if used with doravirine200 Tenofovir DF: No clinically important pharmacokinetic interactions with tacrolimus1 221 |
Cyclosporine, everolimus, sirolimus, tacrolimus: Dosage adjustments not needed if used with doravirine200 |
Lamivudine |
No clinically important pharmacokinetic interactions between doravirine, lamivudine, and tenofovir DF1 No in vitro evidence of antagonistic antiretroviral effects between doravirine and lamivudine or tenofovir DF1 |
|
Ledipasvir and sofosbuvir |
Fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir): No clinically important pharmacokinetic interactions with doravirine;1 14 increased tenofovir exposures1 200 |
Ledipasvir/sofosbuvir: Dosage adjustments not needed if used with doravirine/lamivudine/tenofovir DF;14 200 monitor for tenofovir-associated adverse effects1 200 |
Lofexidine |
No effect on lofexidine concentrations expected if used with doravirine200 |
Dosage adjustments not needed if used with doravirine200 |
Macrolides |
Azithromycin: No effect on azithromycin concentrations expected if used with doravirine200 Clarithromycin: Possible increased doravirine concentrations; no effect on clarithromycin concentrations expected if used with doravirine200 Erythromycin: Possible increased doravirine concentrations200 |
Azithromycin: Dosage adjustments not needed if used with doravirine200 Clarithromycin: Experts state consider alternative (e.g., azithromycin) for prophylaxis or treatment of M. avium complex (MAC) infections in patients receiving doravirine200 Erythromycin: Experts state monitor for doravirine tolerability200 |
Methadone |
Doravirine and tenofovir DF: No clinically important effects on pharmacokinetics of methadone or either antiretroviral1 12 200 |
Dosage adjustments not needed if used with doravirine200 |
Mitotane |
Decreased doravirine concentrations expected; possible decreased doravirine efficacy1 200 |
Concomitant use contraindicated;1 200 do not initiate doravirine/lamivudine/tenofovir DF until ≥4 weeks after mitotane discontinued1 |
Nefazodone |
Doravirine: Possible increased doravirine concentrations200 |
Doravirine: Experts state monitor for doravirine-associated adverse effects200 |
NSAIAs |
High-dose or multiple NSAIAs: Possible increased concentrations of lamivudine, tenofovir, and/or the NSAIAs1 221 |
Avoid doravirine/lamivudine/tenofovir DF in patients who are receiving or have recently received a nephrotoxic drug (e.g., high-dose or multiple NSAIAs)1 |
Olanzapine |
Doravirine: No clinically important effect on olanzapine concentrations expected200 |
Doravirine: Experts state dosage adjustments not needed200 |
Phosphodiesterase type 5 (PDE5) inhibitors |
Avanafil, sildenafil, tadalafil, vardenafil: No effect on PDE5 inhibitor concentrations expected10 200 |
Avanafil, sildenafil, tadalafil, vardenafil: Dosage adjustments not needed if used with doravirine200 |
Platelet-aggregation inhibitors |
Clopidogrel, prasugrel: No effect on platelet-aggregation inhibitor concentrations expected if used with doravirine200 |
Clopidogrel, prasugrel: Dosage adjustments not needed if used with doravirine200 |
Proton-pump inhibitors |
Pantoprazole: No clinically important effect on doravirine concentrations1 11 Other proton-pump inhibitors: No effect on doravirine concentrations expected200 |
Pantoprazole and other proton-pump inhibitors: Dosage adjustments not needed if used with doravirine200 |
Ribavirin |
Tenofovir DF: No clinically important pharmacokinetic interactions200 |
Tenofovir DF: Dosage adjustment not needed200 |
St. John's wort (Hypericum perforatum) |
Decreased doravirine concentrations expected; possible decreased doravirine efficacy1 200 |
Concomitant use contraindicated;1 200 do not initiate doravirine/lamivudine/tenofovir DF until ≥4 weeks after St. John's wort discontinued1 |
Sofosbuvir |
Tenofovir DF: No clinically important pharmacokinetic interactions1 221 |
|
Sofosbuvir and velpatasvir |
Fixed combination of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir): Possible increased tenofovir concentrations and AUC;1 200 221 no clinically important pharmacokinetic interactions with doravirine expected200 |
Sofosbuvir/velpatasvir: Monitor for tenofovir-associated adverse effects1 200 221 |
Sofosbuvir, velpatasvir, and voxilaprevir |
Fixed combination of sofosbuvir, velpatasvir, and voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir): Possible increased tenofovir concentrations and AUC;1 200 221 no clinically important pharmacokinetic interactions with doravirine expected200 |
Sofosbuvir/velpatasvir/voxilaprevir: Monitor for tenofovir-associated adverse effects1 200 221 |
Sorbitol |
Lamivudine: Decreased lamivudine AUC and peak plasma concentrations1 219 |
Avoid concomitant use of doravirine/lamivudine/tenofovir DF and sorbitol-containing drugs1 |
SSRIs |
Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline: No effect on SSRI concentrations expected if used with doravirine200 |
Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline: Dosage adjustments not needed if used with doravirine200 |
Tenofovir |
No clinically important pharmacokinetic interactions between doravirine, lamivudine, and tenofovir DF1 No in vitro evidence of antagonistic antiretroviral effects between doravirine and lamivudine or tenofovir DF1 |
|
Trazodone |
No effect on trazodone concentrations expected if used with doravirine200 |
Dosage adjustments not needed if used with doravirine200 |
Doravirine, Lamivudine, and Tenofovir Disoproxil Pharmacokinetics
Absorption
Bioavailability
Doravirine: 64%.1
Lamivudine: 86%.1
Tenofovir DF: 25%.1
Food
Relative to fasting state, administration of doravirine, lamivudine, and tenofovir DF with high-fat meal increases AUC of doravirine and tenofovir by 10 and 25%, respectively, and decreases lamivudine AUC by 7%.1
Effect of food not considered clinically important.1
Plasma Concentrations
A fixed-combination tablet containing doravirine 100 mg, lamivudine 300 mg, and tenofovir DF 300 mg is bioequivalent to a 100-mg tablet of doravirine, 300-mg tablet of lamivudine, and 300-mg tablet of tenofovir DF given simultaneously.1
Peak plasma concentrations of doravirine and tenofovir occur 2 hours and 1 hour, respectively, after oral administration.1
Distribution
Extent
Doravirine: Distributed into milk in rats;1 not known whether distributed into human milk.1
Lamivudine and tenofovir DF: Distributed into human milk.1 202
Plasma Protein Binding
Doravirine: 76%.1
Lamivudine: <35%.1
Tenofovir: <0.7%.1
Elimination
Metabolism
Doravirine: Primarily metabolized by CYP3A.1
Lamivudine: Metabolized by CYP isoenzymes only to a minor extent.1 219
Tenofovir DF: Does not undergo hepatic metabolism.1 221
Elimination Route
Doravirine: Approximately 6% of oral dose eliminated in urine as unchanged doravirine;1 24 255 unchanged drug also eliminated to a minor extent by biliary and/or fecal routes.1 255
Lamivudine: Eliminated by glomerular filtration and active tubular secretion;1 219 following an IV dose, approximately 71% eliminated in urine.219 221
Tenofovir: Eliminated by glomerular filtration and active tubular secretion;1 221 following an IV dose, 70–80% eliminated in urine.221
Half-life
Doravirine: 15 hours.1
Lamivudine: 5–7 hours.1
Tenofovir: 17 hours.1
Special Populations
Hepatic impairment: Doravirine pharmacokinetics not substantially affected by moderate hepatic impairment (Child-Pugh class B).1 27 Lamivudine pharmacokinetics not substantially affected by diminishing hepatic function.1 Tenofovir pharmacokinetics not substantially affected by any degree of hepatic impairment.1
Renal impairment: Doravirine exposures 43% higher in individuals with severe renal impairment compared with those without renal impairment.1 28 Based on population pharmacokinetic analysis, renal function does not have a clinically important effect on doravirine pharmacokinetics;1 25 insufficient data in patients with end-stage renal disease and not studied in patients receiving dialysis.1 Lamivudine exposures, peak plasma concentrations, and half-life increased and clearance decreased to a clinically important extent with diminishing renal function (Clcr 111 to < 10 mL/minute).1 Tenofovir exposures and peak plasma concentrations substantially increased in those with Clcr <50 mL/minute or with end-stage renal disease requiring dialysis.1
No clinically important differences in pharmacokinetics based on age in adults (doravirine), race (doravirine, lamivudine), body mass index (BMI) (doravirine), or sex (doravirine, lamivudine, tenofovir DF).1 25 29 255
Stability
Storage
Oral
Tablets
20–25°C (may be exposed to 15–30°C).1
Store in original bottle.1 Protect from moisture;1 do not remove desiccant and keep bottle tightly closed.1
Actions and Spectrum
-
Doravirine/lamivudine/tenofovir DF is a fixed-combination antiretroviral containing doravirine, lamivudine, and tenofovir DF.1
-
Doravirine is a pyridinone HIV NNRTI antiretroviral.1 255 Inhibits replication of HIV-1 by interfering with viral polymerase activities of reverse transcriptase.1 17 18 19 Inhibits polymerization reaction by noncompetitive, non-active site binding to reverse transcriptase causing conformational changes within active site that result in an inactive conformation.17 19 Active against HIV-1, including certain strains resistant to some other NNRTIs.1 17 18 19 21 22 23
-
Lamivudine is an HIV NRTI.1 219 Prodrug that is inactive until converted intracellularly to an active 5′-triphosphate metabolite (lamivudine triphosphate).1 219 After conversion, acts as a reverse transcriptase inhibitor via DNA chain termination after incorporation of the nucleotide analogue.1 219 Active against HIV-1;1 also active against HBV.200
-
Tenofovir DF is a nucleotide reverse transcriptase inhibitor antiretroviral classified as an HIV NRTI.1 221 Prodrug that is inactive until it undergoes diester hydrolysis in vivo to tenofovir and is subsequently metabolized to the active metabolite (tenofovir diphosphate).1 221 Active against HIV-1 and has some in vitro activity against HIV-2;1 221 also active against HBV.200 221
-
HIV-1 strains resistant to doravirine, lamivudine, or tenofovir produced in vitro and have emerged during doravirine/lamivudine/tenofovir DF therapy.1 One or more primary mutations associated with resistance to doravirine identified in HIV-1 isolates from patients who received doravirine/lamivudine/tenofovir DF and were included in the resistance analysis subset (i.e., those with plasma HIV-1 RNA levels exceeding 400 copies/mL at virologic failure or early study discontinuation with resistance data);1 genotypic resistance against lamivudine and tenofovir DF also identified.1
-
Cross-resistance occurs among HIV NNRTIs (e.g., efavirenz, etravirine, nevirapine, rilpivirine).1 Treatment-emergent doravirine resistance-associated substitutions can confer cross-resistance to other NNRTIs;1 however, treatment-emergent doravirine resistance-associated substitution Y318F does not appear to confer reduced susceptibility to efavirenz, etravirine, or rilpivirine.1 Cross-resistance also occurs among HIV NRTIs.1
Advice to Patients
-
Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.200 Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.1 200
-
Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.200
-
Advise patients that early initiation of antiretroviral therapy and sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to acquired immunodeficiency syndrome (AIDS) and death.200
-
Advise patients that effective antiretroviral regimens can decrease HIV levels in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.200 Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids) and reducing high-risk behaviors (e.g., reusing or sharing needles).200
-
Importance of reading patient information provided by the manufacturer.1
-
Advise patients to take doravirine/lamivudine/tenofovir DF once every day at a regularly scheduled time with or without food.1
-
Advise patients not to miss or skip doses since this can result in development of resistance.1 If a patient forgets to take doravirine/lamivudine/tenofovir DF, tell the patient to take the missed dose right away, unless it is almost time for the next dose.1 Advise the patient not to take 2 doses at one time and to take the next dose at the regularly scheduled time.1
-
Inform patients that testing for HBV infection is recommended before antiretroviral therapy is initiated.1 Also advise patients that severe acute exacerbations of HBV infection have been reported following discontinuance of lamivudine or tenofovir DF (components of doravirine/lamivudine/tenofovir DF) in HIV-infected patients coinfected with HBV.1 Importance of not discontinuing doravirine/lamivudine/tenofovir DF without consulting a clinician.1
-
Inform patients that renal impairment, including cases of acute renal failure or Fanconi syndrome, has occurred in association with use of tenofovir DF (a component of doravirine/lamivudine/tenofovir DF).1 Importance of not using doravirine/lamivudine/tenofovir DF concomitantly with or shortly after nephrotoxic agents (e.g., high-dose or multiple NSAIAs).1
-
Inform patients that decreased BMD has occurred with the use of tenofovir DF (a component of doravirine/lamivudine/tenofovir DF) and that assessment of BMD should be considered in those with a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss.1
-
Advise patients that doravirine/lamivudine/tenofovir DF may interact with certain other drugs.1 For patients receiving rifabutin, importance of taking one 100-mg tablet of single-entity doravirine once daily approximately 12 hours after taking doravirine/lamivudine/tenofovir DF.1
-
Inform patients that signs and symptoms of inflammation from other previous infections may occur soon after initiation of antiretroviral therapy in some patients with advanced HIV infection (AIDS).1 These symptoms may be due to an improvement in immune response, enabling the body to fight infections that may have been present with no obvious symptoms.1 Importance of immediately informing a clinician if any symptoms of infection occur.1
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements (e.g., St. John’s wort), as well as any concomitant illnesses.1
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise HIV-infected women not to breast-feed.1 202
-
Importance of advising patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Tablets, film-coated |
Doravirine 100 mg, Lamivudine 300 mg, and Tenofovir Disoproxil Fumarate 300 mg |
Delstrigo |
Merck |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions March 30, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
References
1. Merck & Co. Delstrigo (doravirine, lamivudine, and tenofovir disoproxil fumarate) tablets prescribing information. Whitehouse Station, NJ; 2019 Oct.
2. Orkin C, Molina JM, Lombaard J et al. Once-Daily Doravirine in HIV-1-Infected, Antiretroviral-Naive Adults: An Integrated Efficacy Analysis. Clin Infect Dis. 2019; http://www.ncbi.nlm.nih.gov/pubmed/31121015?dopt=AbstractPlus
3. Orkin C, Squires KE, Molina JM et al. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial. Clin Infect Dis. 2019; 68:535-544. http://www.ncbi.nlm.nih.gov/pubmed/30184165?dopt=AbstractPlus
7. Khalilieh S, Yee KL, Sanchez RI et al. Results of a Doravirine-Atorvastatin Drug-Drug Interaction Study. Antimicrob Agents Chemother. 2017; 61 http://www.ncbi.nlm.nih.gov/pubmed/27872071?dopt=AbstractPlus
8. Yee KL, Khalilieh SG, Sanchez RI et al. The Effect of Single and Multiple Doses of Rifampin on the Pharmacokinetics of Doravirine in Healthy Subjects. Clin Drug Investig. 2017; 37:659-667. http://www.ncbi.nlm.nih.gov/pubmed/28353169?dopt=AbstractPlus
9. Sanchez RI, Yee KL, Fan L et al. Evaluation of the Pharmacokinetics of Metformin Following Coadministration With Doravirine in Healthy Volunteers. Clin Pharmacol Drug Dev. 2019; http://www.ncbi.nlm.nih.gov/pubmed/30973682?dopt=AbstractPlus
10. Kreutzwiser D, Tseng A. Drug interactions between antiretrovirals and drugs used to treat benign prostatic hyperplasia/lower urinary tract symptoms. Expert Opin Drug Metab Toxicol. 2016; 12:1211-24. http://www.ncbi.nlm.nih.gov/pubmed/27376653?dopt=AbstractPlus
11. Khalilieh SG, Yee KL, Sanchez RI et al. A Study to Evaluate Doravirine Pharmacokinetics When Coadministered With Acid-Reducing Agents. J Clin Pharmacol. 2019; http://www.ncbi.nlm.nih.gov/pubmed/30817001?dopt=AbstractPlus
12. Khalilieh S, Yee KL, Sanchez RI et al. Evaluation of the Pharmacokinetic Interaction Between Doravirine and Methadone. Clin Pharmacol Drug Dev. 2019; http://www.ncbi.nlm.nih.gov/pubmed/31120195?dopt=AbstractPlus
13. Khalilieh SG, Yee KL, Sanchez RI et al. Multiple Doses of Rifabutin Reduce Exposure of Doravirine in Healthy Subjects. J Clin Pharmacol. 2018; http://www.ncbi.nlm.nih.gov/pubmed/29723418?dopt=AbstractPlus
14. Ankrom W, Sanchez RI, Yee KL et al. Investigation of Pharmacokinetic Interactions between Doravirine and Elbasvir-Grazoprevir and Ledipasvir-Sofosbuvir. Antimicrob Agents Chemother. 2019; 63 http://www.ncbi.nlm.nih.gov/pubmed/30782982?dopt=AbstractPlus
15. Khalilieh SG, Yee KL, Sanchez RI et al. Doravirine and the Potential for CYP3A-Mediated Drug-Drug Interactions. Antimicrob Agents Chemother. 2019; 63 http://www.ncbi.nlm.nih.gov/pubmed/30783000?dopt=AbstractPlus
16. Bleasby K, Fillgrove KL, Houle R et al. In Vitro Evaluation of the Drug Interaction Potential of Doravirine. Antimicrob Agents Chemother. 2019; 63 http://www.ncbi.nlm.nih.gov/pubmed/30745395?dopt=AbstractPlus
17. Lai MT, Feng M, Falgueyret JP et al. In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother. 2014; 58:1652-63. http://www.ncbi.nlm.nih.gov/pubmed/24379202?dopt=AbstractPlus
18. Côté B, Burch JD, Asante-Appiah E et al. Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses. Bioorg Med Chem Lett. 2014; 24:917-22. http://www.ncbi.nlm.nih.gov/pubmed/24412110?dopt=AbstractPlus
19. Namasivayam V, Vanangamudi M, Kramer VG et al. The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic. J Med Chem. 2019; 62:4851-4883. http://www.ncbi.nlm.nih.gov/pubmed/30516990?dopt=AbstractPlus
21. Feng M, Wang D, Grobler JA et al. In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways. Antimicrob Agents Chemother. 2015; 59:590-8. http://www.ncbi.nlm.nih.gov/pubmed/25385110?dopt=AbstractPlus
22. Feng M, Sachs NA, Xu M et al. Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor-Associated Mutants at Clinically Relevant Concentrations. Antimicrob Agents Chemother. 2016; 60:2241-7. http://www.ncbi.nlm.nih.gov/pubmed/26833152?dopt=AbstractPlus
23. Sterrantino G, Borghi V, Callegaro AP et al. Prevalence of predicted resistance to doravirine in HIV-1-positive patients after exposure to non-nucleoside reverse transcriptase inhibitors. Int J Antimicrob Agents. 2019; 53:515-519. http://www.ncbi.nlm.nih.gov/pubmed/30769200?dopt=AbstractPlus
24. Anderson MS, Gilmartin J, Cilissen C et al. Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects. Antivir Ther. 2015; 20:397-405. http://www.ncbi.nlm.nih.gov/pubmed/25470746?dopt=AbstractPlus
25. Yee KL, Ouerdani A, Claussen A et al. Population Pharmacokinetics of Doravirine and Exposure-Response Analysis in Individuals with HIV-1. Antimicrob Agents Chemother. 2019; 63 http://www.ncbi.nlm.nih.gov/pubmed/30745394?dopt=AbstractPlus
26. Behm MO, Yee KL, Liu R et al. The Effect of Food on Doravirine Bioavailability: Results from Two Pharmacokinetic Studies in Healthy Subjects. Clin Drug Investig. 2017; 37:571-579. http://www.ncbi.nlm.nih.gov/pubmed/28349328?dopt=AbstractPlus
27. Khalilieh S, Yee KL, Liu R et al. Moderate Hepatic Impairment Does Not Affect Doravirine Pharmacokinetics. J Clin Pharmacol. 2017; 57:777-783. http://www.ncbi.nlm.nih.gov/pubmed/28026013?dopt=AbstractPlus
28. Ankrom W, Yee KL, Sanchez RI et al. Severe Renal Impairment Has Minimal Impact on Doravirine Pharmacokinetics. Antimicrob Agents Chemother. 2018; 62 http://www.ncbi.nlm.nih.gov/pubmed/29891610?dopt=AbstractPlus
29. Behm MO, Yee KL, Fan L et al. Effect of gender and age on the relative bioavailability of doravirine: results of a Phase I trial in healthy subjects. Antivir Ther. 2017; 22:337-344. http://www.ncbi.nlm.nih.gov/pubmed/28206979?dopt=AbstractPlus
30. Johnson M, Kumar P, Molina JM et al. Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial. J Acquir Immune Defic Syndr. 2019; 81:463-472. http://www.ncbi.nlm.nih.gov/pubmed/30985556?dopt=AbstractPlus
200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Accessed January 2, 2020. Updates may be available at HHS AIDS Information (AIDSinfo) website. https://aidsinfo.nih.gov/
201. Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection. Accessed January 2, 2020. Updates may be available at HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov
202. Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for the use of antiretroviral drugs in pregnant women with HIV infection and interventions to reduce perinatal HIV transmission in the United States. Accessed January 2, 2020. Updates may be available at HHS AIDS Information (AIDSinfo) website. https://aidsinfo.nih.gov/
219. ViiV Healthcare. Epivir (lamivudine) tablet, film coated and solution prescribing information. Research Triangle Park, NC; 2019 May.
221. Gilead Sciences. Viread (tenofovir disoproxil fumarate) tablets and powder for oral use prescribing information. Foster City, CA; 2019 Apr.
255. Merck & Co. Pifeltro (doravirine) tablets prescribing information. Whitehouse Station, NJ. 2019 Oct.
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