Bictegravir/emtricitabine/tenofovir alafenamide, sold under the brand name Biktarvy, is a

fixed-dose combination A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...

antiretroviral medication The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of mul ...

for the treatment of

HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

. It contains

bictegravir Bictegravir (INN; BIC, formerly known as GS-9883) is a second-generation integrase inhibitor (INSTI) class that was structurally derived from an earlier compound dolutegravir by scientists at Gilead Sciences. ''In vitro'' and clinical results ...

, a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor;

emtricitabine Emtricitabine (commonly called FTC, systematic name 2',3'-dideoxy-5-fluoro-3'-thiacytidine), with trade name Emtriva (formerly Coviracil), is a nucleoside reverse-transcriptase inhibitor (NRTI) for the prevention and treatment of HIV infection ...

, an HIV-1 nucleoside analog reverse transcriptase inhibitor; and

tenofovir alafenamide Tenofovir alafenamide, sold under the brand name Vemlidy, is an antiviral medication used against hepatitis B and HIV. It is used for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease an ...

, an HIV-1 nucleoside analog reverse transcriptase inhibitor. It was approved for use in 2018 in Australia, the European Union Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. and the United States and in 2019 in New Zealand and the United Kingdom; a generic version was approved by the

Drugs Controller General of India A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via inhalation, injection, smoking, ingestion ...

in 2019. it is recommended as a first-line choice of antiretroviral therapy in several countries, including the European Union, the United Kingdom and the United States.

Medical uses

The combination is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of human immunodeficiency virus 1 (HIV 1) infection in people weighing at least without present or past evidence of viral resistance to the integrase inhibitor class, emtricitabine or tenofovir.

Side effects

The US FDA prescription label contains a

boxed warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears near the beginning of the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administratio ...

about acute exacerbations of hepatitis B. Adverse drug reactions include, but are not limited to, diarrhea, nausea, and headache.

Combination therapy

Bictegravir/emtricitabine/tenofovir alafenamide is an example of a combination drug that can be taken as a complete regimen for the treatment of the human immunodeficiency virus.

Combination therapy In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are ...

for HIV, often called

highly active antiretroviral therapy The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of mul ...

(HAART), is composed of two or more types of antiretroviral drugs. Combination therapy decreases the likelihood that drug resistance will occur, because it is unlikely that the HIV-1 strains will be able to mutate enough to become resistant to all drugs being used in the combination. Combination therapy increases the length of lives of patients with HIV-1, and can greatly reduce the possibility for transmission of the virus.

Components

Bictegravir Bictegravir (INN; BIC, formerly known as GS-9883) is a second-generation integrase inhibitor (INSTI) class that was structurally derived from an earlier compound dolutegravir by scientists at Gilead Sciences. ''In vitro'' and clinical results ...

(BIC) is an integrase strand transfer inhibitor (INSTI). Bictegravir is different from other INSTIs because it contains a bridged bicyclic ring and a distinct benzyl tail with a 2,4,6-trifluorobenzyl group. This contributes to an increase in plasma protein binding and a reduction of activation of the

pregnane X receptor In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the ' ...

(PXR). These changes minimize interactions between drugs, lower clearance, and increase solubility. Bictegravir was found to be less drug resistant than other drugs in the same class.

Emtricitabine Emtricitabine (commonly called FTC, systematic name 2',3'-dideoxy-5-fluoro-3'-thiacytidine), with trade name Emtriva (formerly Coviracil), is a nucleoside reverse-transcriptase inhibitor (NRTI) for the prevention and treatment of HIV infection ...

(FTC) is a

nucleoside reverse transcriptase inhibitor Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication ...

(NRTI) that is a synthetic fluoro derivative of thiacytidine. Within the cell, emtricitabine becomes phosphorylated, which forms emtricitabine 5′-triphosphate within the cell. This allows for the drug to compete with the viral and host substrate and ultimately causes a termination of DNA chain elongation. Underlying

hepatitis B virus Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus '' Orthohepadnavirus'' and a member of the '' Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B. Classification Hepatitis B ...

(HBV) can interact with emtricitabine to cause significant liver damage, but it does not have a significant detrimental effect on the liver when given to patients without HBV.

Tenofovir alafenamide Tenofovir alafenamide, sold under the brand name Vemlidy, is an antiviral medication used against hepatitis B and HIV. It is used for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease an ...

(TAF) is a

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

of tenofovir that functions as a nucleotide reverse transcriptase inhibitor (NtRTI). Other prodrugs for tenofovir have been tested, but TAF is more efficient at refining HIV-1 therapy. It converts intracellularly to TFV diphosphate, which is a metabolite in HIV target cells. Thus, TAF has higher active metabolite concentrations and lower plasma TFV than other Tenofovir prodrugs. TAF is metabolized primarily with the kidneys, and has a lower dosage than other prodrugs, so it is less detrimental to the renal elimination system.

Research

Bictegravir/emtricitabine/tenofovir alafenamide has been investigated for

post-exposure prophylaxis Post-exposure prophylaxis, also known as post-exposure prevention (PEP), is any preventive medical treatment started after exposure to a pathogen in order to prevent the infection from occurring. It should be contrasted with pre-exposure prophy ...

(PEP) for preventing HIV infection after exposure and has shown positive early results. However, it has not been approved for this use as of 2024.

Economics

In 2023, the Institute for Clinical and Economic Review (ICER) identified Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide), developed by Gilead Sciences, as one of five high-expenditure drugs that experienced significant net price increases without new clinical evidence to justify the hikes. Specifically, Biktarvy's wholesale acquisition cost rose by 5.49%, leading to an additional $815 million in costs to U.S. payers.

References

{{DEFAULTSORT:Bictegravir Emtricitabine Tenofovir Alafenamide Fixed dose combination (antiretroviral)