This is a compilation of information and the history of treatments/antiretrovirals used for HIV and other retroviruses.
The first drugs used for HIV were both in use in clinical trials in 1987. The first drug was a reverse transcriptase drug called (zidovudine) also known as AZT.
AZT — were heralded as a “breakthrough” and “the light at the end of the tunnel” by the company, and pushed the FDA approve the first AIDS medication on March 19, 1987, in a record 20 months. https://time.com/4705809/first-aids-drug-azt/
The second drug was Saquinavir (which is a protease inhibitor). 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. https://en.wikipedia.org/wiki/Discovery_and_development_of_HIV-protease_inhibitors
Saquinavir was patented in 1988 and first sold in 1995.[3][4] As of 2015 it is not available as a generic medication in the United States and is expensive.[5] The wholesale cost in the developing world is about 4.50 USD per day.[6
Saquinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease.
Protease inhibitors prevent viral replication by selectively binding to viral proteases(e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.
Protease inhibitors were the second class of antiretroviral drugs developed. The first members of this class, saquinavir and ritonavir, were approved in late 1995–1996. Within 2 years, annual deaths from AIDS in the United States fell from over 50,000 to approximately 18,000[2] Prior to this the annual death rate had been increasing by approximately 20% each year.
The NNRTIs are HIV-1 specific and have no activity against HIV-2 and other retroviruses. The first NNRTI, nevirapine was discovered by researchers at Boehringer Ingelheim and approved by the FDA in 1996. In the next two years two other NNRTIs were approved by the FDA, delavirdine in 1997 and efavirenz in 1998.[4] These three drugs are so-called first generation NNRTIs. The need for NNRTIs with better resistance profile led to the development of the next generation of NNRTIs. Researchers at Janssens Foundation and Tibotec discovered the first drug in this class, etravirine, which was approved by the FDA in 2008. The second drug in this class, rilpivirine, was also discovered by Tibotec and was approved by the FDA in 2011. In addition to these four NNRTIs several other are in clinical development.[7]
Discovery and development of NNRTIs began in the late 1980s[2] and in the end of 2009 four NNRTI had been approved by regulatory authorities and several others were undergoing clinical development. Drug resistance develops quickly if NNRTIs are administered as monotherapy and therefore NNRTIs are always given as part of combination therapy, the highly active antiretroviral therapy (HAART).[3]
Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are antiretroviral drugs used in the treatment of human immunodeficiency virus (HIV). NNRTIs inhibit reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of HIV. RT is one of the most popular targets in the field of antiretroviral drug development.[1]
Timeline and first drug trials:
1987
AZT (zidovudine), the first antiretroviral drug, becomes available to treat HIV.[11][61]
On August 18 the FDA sanctioned the first clinical trial to test an HIV vaccine candidate in a research participant.[45]
AZT — were heralded as a “breakthrough” and “the light at the end of the tunnel” by the company, and pushed the FDA approve the first AIDS medication on March 19, 1987, in a record 20 months. https://time.com/4705809/first-aids-drug-azt/
The second drug was Saquinavir (which is a protease inhibitor). 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. https://en.wikipedia.org/wiki/Discovery_and_development_of_HIV-protease_inhibitors
Saquinavir was patented in 1988 and first sold in 1995.[3][4] As of 2015 it is not available as a generic medication in the United States and is expensive.[5] The wholesale cost in the developing world is about 4.50 USD per day.[6
Saquinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease.
Protease inhibitors prevent viral replication by selectively binding to viral proteases(e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.
Protease inhibitors were the second class of antiretroviral drugs developed. The first members of this class, saquinavir and ritonavir, were approved in late 1995–1996. Within 2 years, annual deaths from AIDS in the United States fell from over 50,000 to approximately 18,000[2] Prior to this the annual death rate had been increasing by approximately 20% each year.
The NNRTIs are HIV-1 specific and have no activity against HIV-2 and other retroviruses. The first NNRTI, nevirapine was discovered by researchers at Boehringer Ingelheim and approved by the FDA in 1996. In the next two years two other NNRTIs were approved by the FDA, delavirdine in 1997 and efavirenz in 1998.[4] These three drugs are so-called first generation NNRTIs. The need for NNRTIs with better resistance profile led to the development of the next generation of NNRTIs. Researchers at Janssens Foundation and Tibotec discovered the first drug in this class, etravirine, which was approved by the FDA in 2008. The second drug in this class, rilpivirine, was also discovered by Tibotec and was approved by the FDA in 2011. In addition to these four NNRTIs several other are in clinical development.[7]
Discovery and development of NNRTIs began in the late 1980s[2] and in the end of 2009 four NNRTI had been approved by regulatory authorities and several others were undergoing clinical development. Drug resistance develops quickly if NNRTIs are administered as monotherapy and therefore NNRTIs are always given as part of combination therapy, the highly active antiretroviral therapy (HAART).[3]
Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are antiretroviral drugs used in the treatment of human immunodeficiency virus (HIV). NNRTIs inhibit reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of HIV. RT is one of the most popular targets in the field of antiretroviral drug development.[1]
Timeline and first drug trials:
1987
AZT (zidovudine), the first antiretroviral drug, becomes available to treat HIV.[11][61]
On August 18 the FDA sanctioned the first clinical trial to test an HIV vaccine candidate in a research participant.[45]
1991
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.
Saquinavir, a new type of protease inhibitor drug, becomes available to treat HIV. Highly active antiretroviral therapy (HAART) becomes possible.[11][medical citation needed] Within two years, death rates due to AIDS will have plummeted in the developed world.
September 28, jazz legend Miles Davis dies at the age of 65. The official cause of death is bronchial pneumonia. He was taking Zidovudine (AZT) when hospitalized; at the time, Zidovudine (AZT) was a treatment for HIV and AIDS.
September 28, jazz legend Miles Davis dies at the age of 65. The official cause of death is bronchial pneumonia. He was taking Zidovudine (AZT) when hospitalized; at the time, Zidovudine (AZT) was a treatment for HIV and AIDS.
November 24, A little over 24 hours after issuing a statement confirming that he had been tested HIV positive and had AIDS, Freddie Mercury (singer of the British band Queen) dies at the age of 45. The official cause of death is bronchial pneumonia resulting from AIDS.
November 7, NBA star Magic Johnson publicly announces that he is HIV-positive. He is given HIV medication in 1994 with the 2 meds being tried since 1987 in clinical trials. A reverse transcriptase and protease inhibitor med combo. Here is more information:
Magic Johnson is one of the first well known people treated with the first HIV medications, many of which are still in use today:
Magic Johnson receives antiretroviral medication. - According to a Newsweek story from last spring (2011), one of Johnson's doctors who helped pioneer the treatment placed him on the then-experimental drug cocktail in 1994, about a year and a half before it came into widespread use in 1996.
"Magic got a jumpstart on experimental drugs before they were released to the general public," Lieb told Life's Little Mysteries, "but there were many people in clinical trials benefitting at the same time." Researchers have developed a number of powerful drugs to help people like Johnson avoid this fate. The key weapon has been a regimen of three or four antiretroviral drugs, collectively known as highly active antiretroviral therapy, or HAART. The meds that slam dunk HIV - HIV spreads by hijacking a subset of white blood cells called T cells, which are the body's first line of defense against foreign invaders, and using the cells' DNA to make copies of itself or replicate; in this process, these T cells get destroyed. The most common drugs in the HAART regimen target two of the enzymes that HIV uses to replicate itself. Stopping HIV in the back court. The key with Johnson and others has been preventing their incurable disease from progressing into full-blown AIDS. Upon infection with human immunodeficiency virus (HIV), a person's immune system kills off nearly all of the virus and infected cells. But some small number remain, and over time, those HIV cells replicate, and replicate, and replicate. Then, usually 10 years after the initial infection, the viral load reaches a critical count, and the virus begins killing off the vital immune cells that protect us against infections. At that critical count, a person is considered to have acquired immunodeficiency syndrome (AIDS); with the body’s immunological defenses destroyed, it's usually only a matter of months before a range of opportunistic infections and cancers complete their lethal work. Researchers have developed a number of powerful drugs to help people like Johnson avoid this fate. The key weapon has been a regimen of three or four antiretroviral drugs, collectively known as highly active antiretroviral therapy, or HAART. Researchers continue to study long-term nonprogressors for insights on HIV resistance that could help the 33 million people battling the virus.
As Johnson has prominently shown, however, those with HIV can still live productive lives. Lieb has seen many such promising cases in person. "We have very buff-looking, healthy-looking HIV patients who have been infected for ages," Lieb said. "You can't tell the difference between them and you and me." https://www.livescience.com/16909-magic-johnson-hiv-aids-anniversary.html
Another article on Magic Johnson and his antiretroviral therapy: As Johnson fought his doubts, his doctors battled the killer that had infected him. Dr. David Ho had begun experimenting with a promising new weapon: a cocktail of antiretroviral medications that seemed to keep HIV in check and prevent patients from developing full-blown AIDS. And so, in 1994—about a year and a half before the new drug regimen was introduced to the general public—Ho put Johnson on it. "Since we pioneered that therapy, we were able to include Mr. Johnson early, and it made a major difference in his health and overall being," says Ho from his offices at the Aaron Diamond AIDS Research Center in New York. "In the beginning there were many pills he had to take several times a day. That's changed a great deal now, so he doesn't take but a few, and with fewer side effects." Johnson's drug regimen includes the pharmaceuticals Trizivir and Kaletra.
https://www.thedailybeast.com/magic-johnson-20-years-of-living-with-hiv?ref=scroll
2015
New, aggressive strain of HIV discovered in Cuba[96][97] Researchers at the University of Leuven in Belgium say the HIV strain CRF19 can progress to AIDS within two to three years of exposure to virus. Typically, HIV takes approximately 10 years to develop into AIDS. The researchers found that patients with the CRF19 variant had more virus in their blood than patients who had more common strains. Patients with CRF19 may start getting sick before they even know they've been infected, which ultimately means there's a significantly shorter time span to stop the disease's progression. The researchers suspect that fragments of other subsets of the virus fasten to each other through an enzyme which makes the virus more powerful and more easily replicated in the body, thus the faster progression.[97]
2016
Researchers have found that an international study found that almost 2,000 patients with HIV failed to respond to the antiviral drug known as tenofovir. Tenofovir is the main HIV drug treatment. The failure to respond to treatment indicates that the virus' resistance to the medication is becoming increasingly common.[99][100]
First trials with antiretrovirals:
FDA-Approved HIV MedicinesDrug ClassGeneric Name
(Other names and acronyms)
Brand NameFDA Approval DateNucleoside Reverse Transcriptase Inhibitors (NRTIs)
NRTIs block reverse transcriptase, an enzyme HIV needs to make copies of itself. abacavir
(abacavir sulfate, ABC) Ziagen December 17, 1998
emtricitabine
(FTC)
Emtriva July 2, 2003
lamivudine
(3TC) Epivir November 17, 1995
tenofovir disoproxil
fumarate
(tenofovir DF, TDF) Viread October 26, 2001
zidovudine
(azidothymidine, AZT, ZDV)
Retrovir March 19, 1987
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
NNRTIs bind to and later alter reverse transcriptase, an enzyme HIV needs to make copies of itself.
doravirine
(DOR) Pifeltro August 30, 2018
efavirenz
(EFV) Sustiva September 17, 1998
etravirine
(ETR) Intelence
January 18, 2008
nevirapine
(extended-release nevirapine, NVP) Viramune
June 21, 1996
Viramune XR (extended release)
March 25, 2011
rilpivirine
(rilpivirine hydrochloride, RPV)
Edurant May 20, 2011
Protease Inhibitors (PIs)
PIs block HIV protease, an enzyme HIV needs to make copies of itself.
atazanavir
(atazanavir sulfate, ATV)
Reyataz June 20, 2003
darunavir
(darunavir ethanolate, DRV)
Prezista June 23, 2006
fosamprenavir
(fosamprenavir calcium, FOS-APV, FPV)
Lexiva October 20, 2003
ritonavir
(RTV)
*Although ritonavir is a PI, it is generally used as a pharmacokinetic enhancer as recommended in the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV and the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Norvir
March 1, 1996
saquinavir
(saquinavir mesylate, SQV)
Invirase
December 6, 1995
tipranavir
(TPV)
Aptivus
June 22, 2005
Fusion Inhibitors
Fusion inhibitors block HIV from entering the CD4 cellsof the immune system.
enfuvirtide
(T-20)
Fuzeon
March 13, 2003
CCR5 Antagonists
CCR5 antagonists block CCR5 coreceptors on the surface of certain immune cells that HIV needs to enter the cells.
maraviroc
(MVC)
Selzentry
August 6, 2007
Integrase Inhibitors
Integrase inhibitors block HIV integrase, an enzyme HIV needs to make copies of itself.
dolutegravir
(DTG, dolutegravir sodium)
Tivicay
August 13, 2013
raltegravir
(raltegravir potassium, RAL)
Isentress
October 12, 2007
Isentress HD May 26, 2017
Post-Attachment Inhibitors
Post-attachment inhibitors block CD4 receptors on the surface of certain immune cells that HIV needs to enter the cells.
ibalizumab-uiyk
(Hu5A8, IBA, Ibalizumab, TMB-355, TNX-355)
Trogarzo
March 6, 2018
Pharmacokinetic Enhancers
Pharmacokinetic enhancers are used in HIV treatment to increase the effectiveness of an HIV medicine included in an HIV regimen.
cobicistat
(COBI, c)
Tybost
September 24, 2014
Combination HIV Medicines
Combination HIV medicines contain two or more HIV medicines from one or more drug classes.
abacavir and lamivudine
(abacavir sulfate / lamivudine, ABC / 3TC)
Epzicom
August 2, 2004
abacavir, dolutegravir, and lamivudine
(abacavir sulfate / dolutegravir sodium / lamivudine, ABC / DTG / 3TC) Triumeq August 22, 2014
abacavir, lamivudine, and zidovudine
(abacavir sulfate / lamivudine / zidovudine, ABC / 3TC / ZDV)
Trizivir
November 14, 2000
atazanavir and cobicistat
(atazanavir sulfate / cobicistat, ATV / COBI)
Evotaz
January 29, 2015
bictegravir, emtricitabine, and tenofovir alafenamide
(bictegravir sodium / emtricitabine / tenofovir alafenamide fumarate, BIC / FTC / TAF) Biktarvy February 7, 2018
darunavir and cobicistat
(darunavir ethanolate / cobicistat, DRV / COBI)
Prezcobix
January 29, 2015
darunavir, cobicistat, emtricitabine, and tenofovir alafenamide
(darunavir ethanolate / cobicistat / emtricitabine / tenofovir AF, darunavir ethanolate / cobicistat / emtricitabine / tenofovir alafenamide, darunavir / cobicistat / emtricitabine / tenofovir AF, darunavir / cobicistat / emtricitabine / tenofovir alafenamide fumarate, DRV / COBI / FTC / TAF) Symtuza July 17, 2018
dolutegravir and rilpivirine
(dolutegravir sodium / rilpivirine hydrochloride, DTG / RPV) Juluca November 21, 2017
doravirine, lamivudine, and tenofovir disoproxil fumarate
(doravirine / lamivudine / TDF, doravirine / lamivudine / tenofovir DF, DOR / 3TC / TDF) Delstrigo August 30, 2018
efavirenz, emtricitabine, and tenofovir disoproxil fumarate
(efavirenz / emtricitabine / tenofovir DF, EFV / FTC / TDF)
Atripla July 12, 2006
efavirenz, lamivudine, and tenofovir disoproxil fumarate
(EFV / 3TC / TDF) Symfi Lo February 5, 2018
elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
(elvitegravir / cobicistat / emtricitabine / tenofovir alafenamide fumarate, EVG / COBI / FTC / TAF)
Genvoya November 5, 2015
elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate
(QUAD, EVG / COBI / FTC / TDF)
Stribild August 27, 2012
emtricitabine, rilpivirine, and tenofovir alafenamide
(emtricitabine / rilpivirine / tenofovir AF, emtricitabine / rilpivirine / tenofovir alafenamide fumarate, emtricitabine / rilpivirine hydrochloride / tenofovir AF, emtricitabine / rilpivirine hydrochloride / tenofovir alafenamide, emtricitabine / rilpivirine hydrochloride / tenofovir alafenamide fumarate, FTC / RPV / TAF)
Odefsey March 1, 2016
emtricitabine, rilpivirine, and tenofovir disoproxil fumarate
(emtricitabine / rilpivirine hydrochloride / tenofovir disoproxil fumarate, emtricitabine / rilpivirine / tenofovir, FTC / RPV / TDF)
Complera August 10, 2011
emtricitabine and tenofovir alafenamide
(emtricitabine / tenofovir AF, emtricitabine / tenofovir alafenamide fumarate, FTC / TAF)
Descovy April 4, 2016
emtricitabine and tenofovir disoproxil fumarate
(emtricitabine / tenofovir DF, FTC / TDF)
Truvada August 2, 2004
(3TC / ZDV)
Combivir September 27, 1997
Combivir September 27, 1997
lopinavir and ritonavir
(ritonavir-boosted lopinavir, LPV/r, LPV / RTV)
Kaletra September 15, 2000
https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/21/58/fda-approved-hiv-medicines
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