HIV Infection Emergency Listed HIV-1 Protease Inhibitor Overview.

Human immunodeficiency virus (HIV) infection has become a global epidemic, with more than 32 million people dying from HIV-related diseases so far, according to the World Health Organization (WHO), with 770,000 deaths in 2018 alone.
HIV infection can lead to acquired immunodeficiency syndrome (acquired immune deficiency syndrome, AIDS), which can lead to systemic immunodeficiency in patients with severe clinical symptoms such as infections and tumors, which can be extremely harmful.
, drug researchers have been looking for effective anti-HIV drugs.
currently, anti-HIV-1 drugs can be broadly divided into retrovirase inhibitors (RTIs), integrated enzyme inhibitors (INIs), protease inhibitors (PIs) and membrane fusion inhibitors (FIs).
hiv-1 protease inhibitors, as an important class of anti-HIV-1 drugs, play an important role in the treatment of HIV-1 infection.
the FDA currently lists 10 anti-HIV-1 protease inhibitors, including: Saquinavir (Saquinavir, SQV), Ritonavir (Litonavi, RTV), Indinavir ( Dinave, IDV), Nelfinavir (Nifinavir, NFV), Amprenavir (Ampnavir, APV), Fosamprenavir (Fosanawe, Fos-APV), Lopinavir (Lopinave, LPV), Atazanavir (Azanavi, ATV), Tipranavir (TPV) and Darunavir (Darunawe, DRV).
, pharmaceutical workers refer to HIV-1 protease inhibition approved before 2000 as next-generation HIV-1 protease inhibition and second-generation HIV-1 protease inhibition approved after 2000.
figure 1 generation HIV-1 protease inhibition Generation HIV-1 protease inhibition includes: Saquinavir (Saquinavir, SQV), Ritonavir (Litonavi, RTV), Indinavir ( Dinavir, IDV), Nelfinavir (Nifinavir, NFV) and Amprenavir (Ampnavir, APV).
Saquinavir (Saquinavir, SQV) was developed by Roche and was originally introduced in 1995 for HIV/AIDS prevention or treatment, often in association with litonavir or lopinavir/litonavir;
the drug was de-marketed in 2006 due to reduced market demand.
Ritonavir (Ritonavir, RTV) was introduced in 1996 and is commonly used in the treatment of HIV/AIDS along with other protease inhibitors;
Indinavir ( Dinavir, IDV) is an oral HIV-1 protease inhibitor that was also introduced in 1996 for use in the treatment of HIV/AIDS in union with other antiviral drugs, which are currently recommended for hiv/AIDS treatment due to their high side effects.
addition, Nelfinavir (Nifinavir, NFV) and Amprenavir (APV) went on sale in 1997 and 1999, respectively, amprenavir (Ampnavir, APV) has now ceased production and GlaxoSmithKline has replaced it with Fosamprenavir (Fosanavi, Fos-APV), a pre-generation drug version.
2nd generation HIV-1 protease inhibition After 2000, several new second-generation HIV-1 protease inhibitors were approved, including: Lopinavir (Lopinavir, LPV), Fos Amprenavir (Fos-APV), Atazanavir (Azanavi, ATV), Tipranavir (Tiranawe, TPV) and Darunavir (Darunavir, DRV).
Lopinavir (Lopinavir, LPV) is a second-generation HIV-1 protease inhibitor approved for sale in 2000, a pharmacodynamic enhancer, usually used in conjunction with litonave in a fixed dose to fight HIV infection.
Fosamprenavir (Fosanavir, Fos-APV), which was approved by the FDA in 2003, is a pre-ampenavir (Ampnavir, APV) drug with a smaller dose than Amprenavir and a cheaper advantage over other second-generation HIV-1 protease inhibitors.
Atazanavir (Azanavi, ATV), originally approved in 2003, is listed on the WHO Essential Medicines List as one of the safe and effective drugs in the health system;
Tipranavir (TIRAnavir, TPV) was approved by the FDA in June 2005 for treatment of HIV infection and in June 2008 for treatment in children;
Darunavir (Darunavir, DRV) was launched in the United States and the European Union in 2006 and 2007 for the treatment of human immunodeficiency virus (HIV-1) infection in adults and children aged three and over;
in general, after years of efforts by drug workers, the development of HIV-1 protease inhibition has made great progress.
Relatively speaking, the first generation of HIV-1 protease inhibition is generally more obvious gastrointestinal reactions, low oral biousability, easy to produce drug resistance and other problems, while the second generation of HIV-1 protease inhibition to a large extent overcome the first generation of HIV-1 protease inhibition of many problems, successfully overcome the low level of oral biological utilization, drug resistance and side effects.
, there are many excellent new HIV-1 protease inhibition is in development, I believe that in the future will emerge more and more excellent HIV-1 protease inhibition, for the benefit of more patients.
references: 1. Research progress in novel HIV-1 protease reedors, 2019; 2. WHO. HIV fact sheet (EB/OL): Who. int/zh/news-room/fact-sheets/detail/hiv-aids2019; 3. Research progress in the development of HIV-1 protease reedors (2015 - 2019), 2020.