Human immunodeficiency virus (HIV) is a lentivirus that has two major species, HIV-1 which causes the majority of the epidemic, and HIV-2, a close relative whose distribution is concentrated in western Africa. HIV infection was first described in 1981 in San Francisco and New York City. In 1985, HIV was identified as the causative agent of acquired immune deficiency syndrome (AIDS) and its complete genome was immediately available. This knowledge paved the way for the development of selective inhibitors.
HIV-2 carries a slightly lower risk of transmission than HIV-1 and infection tends to progress more slowly to AIDS. In common usage HIV usually implies HIV-1.
HIV-1 protease is one of the best known aspartic proteases, and an attractive target for the treatment of AIDS.
After the discovery of HIV protease it only took 10 years for its first inhibitor to reach the market. The first reports of highly selective antagonists against the HIV protease were revealed in 1987. Phase I trials of saquinavir began in 1989 and it was the first HIV protease inhibitor to be approved for prescription use in 1995. Four months later, two other protease inhibitors, ritonavir and indinavir, were approved. In 2009, ten protease inhibitors have reached the market for treatment against HIV but one protease inhibitor, amprenavir, was withdrawn from the market in 2004.