Genetic Implications: Genetic Implications


Trade Name(s)

  • Triumeq

Ther. Class.
antiretrovirals (combination)

Pharm. Class.
integrase strand transfer inhibitors (dolutegravir)
nucleoside reverse transcriptase inhibitors (abacavir, lamivudine)


Treatment of HIV-1 infection.


  •  Abacavir– Converted inside cells to carbovir triphosphate, its active metabolite. Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase, which in turn terminates viral DNA growth.
  •  Dolutegravir– Inhibits HIV-1 integrase, which is required for viral replication.
  •  Lamivudine– After intracellular conversion to its active form (lamivudine-5-triphosphate), inhibits viral DNA synthesis by inhibiting the enzyme reverse transcriptase.

Therapeutic Effect(s):

Evidence of decreased viral replication and reduced viral load with slowed progression of HIV and its sequelae.



Absorption: Rapidly and extensively (83%) absorbed.

Distribution: Distributes into extravascular space and readily distributes into erythrocytes.

Metabolism and Excretion: Mostly metabolized by the liver; 1.2% excreted unchanged in urine.

Half-life: 1.5 hr.


Absorption: Absorption follows oral administration; bioavailability is unknown.

Distribution: Enters CSF.

Protein Binding: >98.9%.

Metabolism and Excretion: Metabolized primarily by the UGT1A1 enzyme system with some metabolism by CYP3A4. 53% excreted unchanged in feces. Metabolites are renally excreted, minimal renal elimination of unchanged drug. Genetic implication Poor metabolizers of dolutegravir have ↑ levels and ↓ clearance.

Half-life: 14 hr.


Absorption: Well absorbed after oral administration (86% in adults, 66% in infants and children).

Distribution: Distributes into the extravascular space. Some penetration into CSF; remainder of distribution unknown.

Metabolism and Excretion: Mostly excreted unchanged in urine; <5% metabolized by the liver.

Half-life:  Adults– 3.7 hr;  children– 2 hr.

TIME/ACTION PROFILE (blood levels)

POunknownunknown24 hr


Contraindicated in:

  • Hypersensitivity to any component (especially abacavir, rechallenge may be fatal);
  • Resistance to any component;
  • Genetic implication Presence of HLA-B*5701 allele;
  • Concurrent use of dofetilide;
  • Concurrent administration of lamivudine or abacavir alone or in other combination antiretroviral dose forms;
  • Moderate to severe liver impairment;
  • CCr <50 mL/min;
  • Lactation: Breast feeding not recommended for HIV-infected patients.

Use Cautiously in:

  • Underlying hepatitis B or C (may worsen liver function);
  • Patients with HIV-1/HCV coinfection receiving interferon alfa with/without ribavirin (may be at risk for hepatic decompensation, dose alteration or discontinuation of interferon and/or ribavirin may be necessary);
  • Mild hepatic impairment (if dose ↓ of abacavir is necessary, combination should be given as individual components);
  • Women and obesity (↑ risk of lactic acidosis and severe hepatomegaly with steatosis);
  • Underlying cardiovascular disease, including history of hypertension, hyperlipidema, smoking history, or diabetes mellitus;
  • OB:  Use only if potential benefit justifies potential risk to the fetus;
  • Pedi:   Children <40 kg (safety and effectiveness not established).

Adverse Reactions/Side Effects


CNS: fatigue, headache, insomnia




Misc: HYPERSENSITIVITY REACTIONS, immune reconstitution syndrome

* CAPITALS indicate life-threatening.
Underline indicate most frequent.



  • Abacavir:  Alcohol  ↑ blood levels.
  • May ↑  methadone  metabolism in some patients; slight ↑ in  methadone  dosing may be needed.
  • Dolutegravir: May ↑ blood levels and toxicity from  dofetilide ; concurrent use contraindicated.
  • Blood levels and effectiveness are ↓ by  etravirine  (should not be used concurrently without atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir).
  • Blood levels and effectiveness are ↓ by efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, and  rifampin ; ↑ dosage of dolutegravir recommended.
  • Blood levels and effectiveness may be ↓ by  nevirapine ; avoid concurrent use
  • May ↑ blood levels and toxicity from  metformin ; do not exceed metformin dose of 1000 mg/day.
  • Blood levels and effectiveness may be ↓ by other  metabolic inducers  including oxcarbazepine, phenobarbital, and  phenytoin ; avoid concurrent use.
  • Absorption and effectiveness may be ↓ by cation-containing antacids, buffered medications, oral calcium supplements, oral iron supplements, laxatives, or  sucralfate ; dolutegravir should be taken 2 hr before or 6 hr after; may also take dolutegravir and calcium or iron supplements with food.
  • Lamivudine:  Trimethoprim/sulfamethoxazole  ↑ levels (dose alteration may be necessary in renal impairment).
  • ↑ risk of pancreatitis with concurrent use of other  drugs causing pancreatitis.
  • ↑ risk of neuropathy with concurrent use of other  drugs causing neuropathy.
  • Combination therapy with  tenofovir  and  abacavir  may lead to virologic nonresponse; avoid use.
  •  Sorbitol  may ↓ levels; avoid concurrent use.

Drug-Natural Products:

Levels and effectiveness may be ↓  St. John's wort ; avoid concurrent use.


PO (Adults and Children ≥40 kg): One tablet (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg) once daily;  Concurrent efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, carbamazepine, or rifampin– additional 50–mg dose of dolutegravir is required separated by 12 hr.


Tablets: abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg


  • Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections throughout therapy.
  • Assess for signs of hypersensitivity reactions (fever; rash; gastrointestinal–nausea, vomiting, diarrhea, abdominal pain; constitutional–malaise, fatigue, achiness; respiratory–dyspnea, cough, pharyngitis). May also cause elevated liver function tests, increased creatine phosphokinase or serum creatinine, and lymphopenia. Genetic implication Patients who carry the HLA-B*5701 allele are at high risk for hypersensitivity reaction. Discontinue promptly if hypersensitivity reaction is suspected. Regardless of HLA-B*5701 status, permanently discontinue if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Following a hypersensitivity reaction, never restart abacavir-containing products. More severe symptoms may occur within hr and may include life-threatening hypotension and death. Symptoms usually resolve upon discontinuation.
  • May cause lactic acidosis and severe hepatomegaly with steatosis. Monitor patient for signs (↑ serum lactate levels, ↑ liver enzymes, liver enlargement on palpation). Therapy should be suspended if clinical or laboratory signs occur.
  • Assess patient, especially pediatric patients, for signs of pancreatitis (nausea, vomiting, abdominal pain) periodically during therapy. May require discontinuation of therapy.
  • Monitor patient for signs and symptoms of peripheral neuropathy (tingling, burning, numbness, or pain in hands or feet); may be difficult to differentiate from peripheral neuropathy of severe HIV disease. May require discontinuation of therapy.

Lab Test Considerations: Obtain a negative pregnancy test prior to starting therapy.

  • Monitor viral load and CD4 cell count regularly during therapy.
  • Genetic implication Screen for HLA-B*5701 allele prior to initiation of therapy to decrease risk of hypersensitivity reaction. Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir.
  • Monitor liver function periodically. May cause ↑ levels of AST, ALT, and alkaline phosphatase, which usually resolve after interruption of therapy. Patients with concurrent Hepatitis B or C should be followed for at least several mo after stopping therapy. Lactic acidosis may occur with hepatic toxicity, causing hepatic steatosis; may be fatal, especially in women.
  • May cause ↑ serum glucose, lipase, and triglyceride levels.

Potential Diagnoses


  • PO Administer without regard to food.
    • Take  Triumeq  2 hr before or 6 hr after antacids, laxatives, other medications containing aluminum, magnesium, sucralfate, or buffering agents, calcium, or iron. Supplements containing calcium or iron can be taken with  Triumeq  if taken with food.

Patient/Family Teaching

  • Emphasize the importance of taking  Triumeq  as directed. Must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount, and do not stop taking without consulting health care professional. Take missed doses as soon as remembered unless almost time for next dose; do not double doses. Advise patient to read the  Medication Guide  prior to starting therapy and with each Rx refill in case of changes.
  • Instruct patient not to share medication with others.
  • Inform patient that medication does not cure AIDS or prevent associated or opportunistic infections. Medication does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom, and avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of medication are unknown at this time.
  • Advise patient of potential for hypersensitivity reactions that may result in death. Instruct patient to discontinue medication and notify health care professional immediately if symptoms of hypersensitivity or signs of Immune Reconstitution Syndrome (signs and symptoms of inflammation from previous infections) occur. A warning card summarizing symptoms of hypersensitivity is provided with each prescription; instruct patient to carry card at all times.
  • Instruct patient to notify health care professional immediately if symptoms of lactic acidosis (tiredness or weakness, unusual muscle pain, trouble breathing, stomach pain with nausea and vomiting, cold especially in arms or legs, dizziness, fast or irregular heartbeat) or if signs of hepatotoxicity (yellow skin or whites of eyes, dark urine, light-colored stools, lack of appetite for several days or longer, nausea, abdominal pain) occur. These symptoms may occur more frequently in patients that are female, obese, or have been taking medications for a long time.
  • Instruct patient to notify health care professional promptly if signs of peripheral neuropathy or pancreatitis occur.
  • Advise patient to avoid sugarless gum or candy due to sorbitol content; may ↓ medication effectiveness.
  • Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially methadone, St. John's wort, and other antiretrovirals.
  • Rep:  Advise female patient of reproductive potential to use effective contraception and to avoid breast feeding during therapy. Notify health care professional if pregnancy is planned or suspected. Switch to another antiviral regimen during 1st trimester. May consider  Triumeq  during 2nd and 3rd trimesters of pregnancy if expected benefit justifies potential risk to pregnant woman and fetus. Pregnant patients should be encouraged to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263.
  • Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

Evaluation/Desired Outcomes

  • Delayed progression of AIDS, and decreased opportunistic infections in patients with HIV.
  • Decrease in viral load and increase in CD4 cell counts.
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