For natural protease inhibitors, please see protease inhibitor (biology)
Protease inhibitors (PIs) are a class of medication used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new virons.
Given the specificity of the target of these drugs there is the risk, as in antibiotics, of the development of drug-resistant mutated viruses. To reduce this risk it is common to use several different drugs together that are each aimed at different targets.
Protease inhibitors were the second class of antiretroviral drugs developed. In all cases, patents remain in force until 2010 or beyond.
The FDA approved it April 15, 1999, making it the sixteenth FDA-approved antiretroviral. It was the first protease inhibitor approved for twice-a-day dosing instead of needing to be taken every eight hours. The convenient dosing came at a price, as the dose required is 1,200mg, delivered in eight very large gel capsules. Production was discontinued by the manufacturer December 31, 2004, as it has been superseded by fosamprenavir.
Is a pro-drug of amprenavir. The FDA approved it October 20, 2003. The human body metabolizes fosamprenavir in order to form amprenavir, which is the active ingredient. That metabolization increases the duration that amprenavir is available, making fosamprenavir a slow-release version of amprenavir and thus reduces the number of pills required versus standard amprenavir.
It was approved by the Food and Drug Administration (FDA) on June 23, 2006. Several ongoing phase III trials are showing a high efficiency for the PREZISTA/rtv combination being superior to the lopinavir/rtv combination for first-line therapy. Darunavir is the first drug in a long time that didn't come with a price increase. It leapfrogged two other approved drugs of its type, and is matching the price of a third .
Researchers are investigating the use of protease inhibitors developed for HIV treatment as anti-protozoals for use against malaria and gastrointestinal protozoal infections:
A combination of ritonavir and lopinavir was found to have some effectiveness against Giardia infection. 
The drugs saquinavir, ritonavir, and lopinavir have been found to have anti-malarial properties. 
A cysteine protease inhibitor drug was found to cure Chagas disease in mice. 
^ Darunavir-ritonavir more effective than Lopinavir-ritonavir in HIV infected, treatment-experienced patients,The Lancet, Volume 370, Number 9581, 07 July 2007, http://www.thelancet.com/journals/lancet/issue?volume=370&issue=9581
^ Liz Highleyman, Patient Advocates Commend Pricing of New PI Darunavir, http://www.hivandhepatitis.com/recent/2006/ad1/063006_a.html
^ [Darunavir - first molecule to treat drug-resistant HIV, http://www.news-medical.net/?id=19211]
^ [Retaining Efficacy Against Evasive HIV, http://pubs.acs.org/cen/news/84/i34/8434drugdesign.html]
^ Dunn LA, Andrews KT, McCarthy JS, et al (2007). "The activity of protease inhibitors against Giardia duodenalis and metronidazole-resistant Trichomonas vaginalis". Int. J. Antimicrob. Agents29 (1): 98–102. doi:10.1016/j.ijantimicag.2006.08.026. PMID 17137752.
^ Andrews KT, Fairlie DP, Madala PK, et al (2006). "Potencies of human immunodeficiency virus protease inhibitors in vitro against Plasmodium falciparum and in vivo against murine malaria". Antimicrob. Agents Chemother.50 (2): 639–48. doi:10.1128/AAC.50.2.639-648.2006. PMID 16436721.
^ Doyle PS, Zhou YM, Engel JC, McKerrow JH (2007). "A Cysteine Protease Inhibitor Cures Chagas' Disease in an, Immunodeficient Murine Model of Infection". doi:10.1128/AAC.00436-07. PMID 17698625.
A brief history of the development of protease inhibitors by Hoffman La Roche, Abbott, and Merck
Antivirals used against HIV (HAART) (primarily J05)