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| Combination of | |
|---|---|
| Abacavir | nucleoside analogreverse transcriptase inhibitor |
| Dolutegravir | integrase inhibitor |
| Lamivudine | nucleoside analogreverse transcriptase inhibitor |
| Clinical data | |
| Trade names | Triumeq, Triumeq PD |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a617015 |
| License data | |
| Pregnancy category |
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| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| PubChemCID | |
| ChemSpider |
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| KEGG |
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Abacavir/dolutegravir/lamivudine, sold under the brand nameTriumeq among others, is afixed-dose combinationantiretroviral medication for the treatment ofHIV/AIDS.[2] It is a combination of threemedications with different and complementarymechanisms of action:abacavir (reverse transcriptase inhibitor),dolutegravir (integrase inhibitor) andlamivudine (nucleoside analog reverse transcriptase inhibitor).[2]
Abacavir is a nucleotide reverse transcriptase inhibitor.[2] Specifically, abacavir is a guanosine analogue that interferes with HIV viral RNA-dependent DNA polymerase, ultimately resulting in inhibition of replication of HIV.Dolutegravir inhibits the HIV replication cycle by binding to the integrase active site and inhibiting the strand transfer step of HIV-1 DNA integration.Lamivudine is a cytosine analogue that inhibits HIV reverse transcription by terminating the viral DNA chain.[4]
The medication wasdeveloped byViiV Healthcare and was approved for use in the United States and in the European Union in 2014.[3][5][6] The combination is on theWorld Health Organization's List of Essential Medicines.[7]
Abacavir/dolutegravir/lamivudine isindicated for the treatment ofHIV/AIDS in people aged twelve years of age and older who weigh at least 40 kilograms (88 lb).[2][3]
The US FDA prescription label contains aboxed warning of hypersensitivity reactions and exacerbations ofhepatitis B.[2]
The following adverse reactions were reported in <2% of patients:[2][4]
Abacavir/dolutegravir/lamivudine should only be used in pregnancy if the potential benefits outweigh the risks.[2][8]
The USCenters for Disease Control and Prevention (CDC) recommends that HIV-infected mothers do not breastfeed their infants to avoid risking postnatal transmission of HIV.[9][10] This recommendation is coupled with the potential for serious adverse reactions in nursing infants.[medical citation needed] Lamivudine was shown to be excreted in human breast milk.[11]
The patent was filed in April 2006,[12] and expires in October 2027.[13]
The combination was approved for use in the United States and in the European Union in 2014.[5][3]
A year supply of abacavir/dolutegravir/lamivudine costs aroundUS$33,000 as it is under patent and not available as a generic.[4]
In July 2015, ViiV Healthcare struck a deal with Shanghai-based Desano Pharmaceuticals for a cheaper supply of dolutegravir (Tivicay) with the goal of cutting the cost in China and other developing countries. After approval of dolutegravir (Tivicay) in 2014, it came with a retail cost of $14,000 per year in the United States.[14]
Efficacy of abacavir/dolutegravir/lamivudine was demonstrated in antiretroviral treatment-naive participants by SINGLE (ING114467), the randomized, controlled trial and other trials in treatment-naive subjects (seedolutegravir).[citation needed]
In the SINGLE trial, 414 participants received dolutegravir + abacavir/lamivudine once daily and 419 participants received efavirenz/emtricitabine/tenofovir once daily. dolutegravir + abacavir/lamivudine compared toefavirenz/emtricitabine/tenofovir showed a reduction in viral load of HIV-1 RNA <50 copies/mL in 80% of participants compared to 72% of participants, respectively. Furthermore, in participants with baseline plasma viral load of<100,000 and >100,000 copies/mL, dolutegravir + abacavir/lamivudine compared to efavirenz/emtricitabine/tenofovir showed a reduction to <50 copies/mL in 85% and 71% compared to 73% and 72%, respectively.[15]
In addition to the adverse reactions reported in clinical trials, the following adverse reactions have been reported voluntarily from a population of unknown size. As such, it is not always possible to estimate frequency or establish a causal relationship to drug exposure.[11]
Abacavir and/or Lamivudine
The safety and tolerability of Triumeq was evaluated foramyotrophic lateral sclerosis (ALS) patients as part of the Lighthouse trial, an open-label, phase 2a study, conducted in Australia beginning in late 2016 over 24 weeks.[16][17] The study premise washuman endogenous retroviruses, specificallyhuman endogenous retrovirus K (HERV-K) may be a trigger or cause of ALS. Research has linked HERV-K to ALS based on increased nonspecificreverse transcriptase activity in thecerebrospinal fluid and blood of ALS patients, as well as HERV-K being found in the motor neurons of ALS patients. Triumeq was chosen as all three component drugs have good penetration of the central nervous system, particularly dolutegravir, which has high clearance rates for CNS HIV. The study found a significant decrease in HERV-K DNA in serum among study participants and showed a decrease in the slope of clinical progression based on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) of roughly 30%.[17]
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