Integrase inhibitors (INIs) are a class of
antiretroviral drug
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 multiple ...
designed to block the action of
integrase
Retroviral integrase (IN) is an enzyme produced by a retrovirus (such as HIV) that integrates—forms covalent links between—its genetic information into that of the host cell it infects. Retroviral INs are not to be confused with phage int ...
, a viral enzyme that inserts the viral genome into the
DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus. Integrase inhibitors were initially developed for the treatment of
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
infection but have been applied to other retroviruses. The class of integrase inhibitors called integrase strand transfer inhibitors (INSTIs) are in established medical use. Other classes, such as integrase binding inhibitors (INBIs), are still experimental.
The
development of integrase inhibitors led to a first approval for the class by the
U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) on October 12, 2007, for
raltegravir
Raltegravir, sold under the brand name Isentress, is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potential ex ...
(brand name
Isentress).
Research published at the time supported the conclusion that "raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks."
Since integrase inhibitors target a distinct step in the retroviral life cycle, they may be taken in combination with other types of HIV drugs to minimize adaptation by the virus.
They are also useful in
salvage therapy
Salvage therapy, also known as rescue therapy, is a form of therapy given after an ailment does not respond to standard therapy. The most common diseases that require salvage therapy are HIV and various cancers. The term is not clearly defined; it ...
for patients whose virus has mutated and acquired resistance to other drugs.
Drugs in use and under development
In use
*
Raltegravir
Raltegravir, sold under the brand name Isentress, is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potential ex ...
(Isentress), developed by
Merck & Co., was the first INSTI approved by the FDA in October 2007.
*
Elvitegravir
Elvitegravir (EVG) is an integrase inhibitor used to treat HIV infection. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Adm ...
(Vitekta), licensed by
Gilead Sciences
Gilead Sciences, Inc. () is an American biopharmaceutical company headquartered in Foster City, California, that focuses on researching and developing antiviral drugs used in the treatment of HIV/AIDS, hepatitis B, hepatitis C, influenza, and CO ...
from
Japan Tobacco
Hepburn: ''Nippon Senbai Kōsha''
, type = 1985-: Public (''kabushiki gaisha'') 1949-1985: Statutory corporation
, traded_as =
, industry = FoodTobacco
, foundation = 1898 (as Imperial Japanese Tobacco Company)1 June 1949 (as Japan Tobacco ...
, was approved by the U.S.
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
in August 2012, for use in adults starting HIV treatment for the first time as part of the fixed dose combination with
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 in ...
and
tenofovir disoproxil
Tenofovir disoproxil, sold under the trade name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for preven ...
(
elvitegravir/cobicistat/emtricitabine/tenofovir
Elvitegravir/cobicistat/emtricitabine/tenofovir, sold under the brand name Stribild, also known as the Quad pill, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. Elvitegravir, emtricitabine and tenofovir diso ...
). Elvitegravir is a low-molecular-weight, highly selective integrase inhibitor that shares a core structure with
quinolone antibiotic
A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as we ...
s. A similar fixed-dose combination containing tenofovir alafenamide instead of tenofovir disoproxil is offered under the brand name Genvoya (
Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide
Tenofovir alafenamide, sold under the brand name Vemlidy, is a hepatitis B virus (HBV) nucleotide reverse transcriptase inhibitor medication for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disea ...
).
*
Dolutegravir
Dolutegravir (DTG), sold under the brand name Tivicay, is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potentia ...
(Tivicay), licensed by
ViiV Healthcare
ViiV Healthcare ( ) is a pharmaceutical company specializing in the development of therapies for HIV infection that was created as a joint venture by Pfizer and GlaxoSmithKline in November 2009 with both companies transferring their HIV assets ...
, was approved for use in the US in 2013, and in the EU in January 2014.
* The combination drug
bictegravir/emtricitabine/tenofovir alafenamide
Bictegravir/emtricitabine/tenofovir alafenamide, sold under the brand name Biktarvy, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. One tablet, taken orally once daily, contains 50mg bictegravir, 200mg emt ...
(Biktarvy), produced by Gilead Sciences, was approved for use in the United States in 2018.
*
Cabotegravir
Cabotegravir, sold under the brand name Vocabria among others, is a antiretroviral medication used for the treatment of HIV/AIDS. It is available in the form of tablets and as an intramuscular injection, as well as in an injectable combination ...
, developed by ViiV Healthcare, was approved in conjunction with
rilpivirine
Rilpivirine, sold under the brand names Edurant and Rekambys, is a medication, developed by Tibotec, used for the treatment of HIV/AIDS. It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency, longer ...
by the FDA in January 2021 (
cabotegravir/rilpivirine
Cabotegravir/rilpivirine, sold under the brand name Cabenuva, is a co-packaged antiretroviral medication for the treatment of HIV/AIDS. It contains cabotegravir and rilpivirine in a package with two separate injection vials.
The most common ...
).
Under development
*
BI 224436
BI 224436 was an investigational new drug under development for the treatment of HIV infection. BI 224436 is the first non-catalytic site integrase inhibitor (NCINI). It inhibits HIV replication via binding to a conserved allosteric pocket of ...
*
MK-2048
MK-2048 is the Merck & Co. designation for a molecule in its pre-clinical drug discovery that is an integrase inhibitor-class of agent intended to be used against HIV infection. It is a second generation integrase design thought to be superior ...
, a second generation integrase inhibitor, that appears to have a duration of action up to four times longer than raltegravir.
See also
*
Discovery and development of integrase inhibitors
Discovery may refer to:
* Discovery (observation), observing or finding something unknown
* Discovery (fiction), a character's learning something unknown
* Discovery (law), a process in courts of law relating to evidence
Discovery, The Discover ...
References
Further reading
*
External links
HIV Antiretroviral Agents in DevelopmentIntegraseBookFull(PDF)
*
{{HIVpharm
Integrase inhibitors