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 multip ...
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 i ...
, 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 immu ...
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 (FDA) on October 12, 2007, for
raltegravir (brand name
Isentress
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 ...
).
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; ...
for patients whose virus has mutated and acquired resistance to other drugs.
Drugs in use and under development
In use
*
Raltegravir (Isentress), developed by
Merck & Co., was the first INSTI approved by the FDA in October 2007.
*
Elvitegravir (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 ...
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 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 ...
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 (
elvitegravir/cobicistat/emtricitabine/tenofovir). 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 wel ...
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).
*
Dolutegravir (Tivicay), licensed by
ViiV Healthcare, was approved for use in the US in 2013, and in the EU in January 2014.
* The combination drug
bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), produced by Gilead Sciences, was approved for use in the United States in 2018.
*
Cabotegravir, developed by ViiV Healthcare, was approved in conjunction with
rilpivirine by the FDA in January 2021 (
cabotegravir/rilpivirine).
Under development
*
BI 224436
*
MK-2048, 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
References
Further reading
*
External links
HIV Antiretroviral Agents in DevelopmentIntegraseBookFull(PDF)
*
{{HIVpharm
Integrase inhibitors