how was the antiretroviral drug, zidovudine (azt) treatment developed?

AZT, or azidothymidine, was originally developed in the 1960s by a U.S. researcher as way to thwart cancer; the compound was supposed to insert itself into the DNA of a cancer cell and mess with its ability to replicate and produce more tumor cells. But it didn’t work when it was tested in mice and was put aside.

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How has the development of AZT changed HIV treatment?

In 1984, scientist Marty St. Clair and her team determined that zidovudine could help treat HIV. Zidovudine was the first medicine discovered to help treat HIV and prevent the transmission of HIV from affected pregnant women to fetuses in the womb by blocking the virus from passing through the placenta.

How did zidovudine use compare to HIV treatment in the 1980s?

 · AZT, or azidothymidine, was originally developed in the 1960s by a U.S. researcher as way to thwart cancer; the compound was supposed to insert itself into the DNA of a cancer cell and mess with...

What is AZT (zidovudine)?

Zidovudine is also known as azido-deoxythymidine, zidovudine or ZDV. Zidovudine was the first drug approved for the treatment of HIV. It is a nucleoside analog reverse transcriptase inhibitor, or nuke. These drugs block the reverse transcriptase enzyme. This enzyme changes HIV’s genetic material (RNA) into the form of DNA.

When was AZT approved by the FDA?

 · Zidovudine (zye doe' vue deen) is a synthetic analogue of thymidine (3’-azido-3’- deoxythymidine: AZT) that is phosphorylated intracellularly and then acts in competing with the natural substrate, thymidine triphosphate, for incorporation into growing HIV DNA chain causing inhibition of the viral reverse transcriptase and chain termination.

How was AZT administered?

Taking AZT orally, 300 mg twice daily or 200 mg three times daily, beginning 14 to 34 weeks into the pregnancy and continuing at least until birth. Receiving intravenous AZT during labour, until delivery.

Who created AZT treatment?

We learn this week of the death of a medical researcher whose work had a profound impact on the treatment of the AIDS virus. Jerome Horwitz invented the drug AZT. It was approved in 1987, the first drug that significantly helped decrease the devastating death toll of AIDS.

When was antiretroviral therapy created?

Many developed countries initiated ART in 1996, but most developing countries began providing it around 2003.

How long did it take to develop AZT?

The time between the first demonstration that AZT was active against HIV in the laboratory and its approval was 25 months, the shortest period of drug development in recent history. AZT was subsequently approved unanimously for infants and children in 1990.

What was AZT originally used for?

AZT, or azidothymidine, was originally developed in the 1960s by a U.S. researcher as way to thwart cancer; the compound was supposed to insert itself into the DNA of a cancer cell and mess with its ability to replicate and produce more tumor cells.

When was AZT approved by the FDA?

AZT (zidovudine) In March of 1987, FDA approved zidovudine (AZT) as the first antiretroviral drug for the treatment of AIDS.

What is the AZT?

AZT, in full azidothymidine, also called zidovudine, drug used to delay development of AIDS (acquired immunodeficiency syndrome) in patients infected with HIV (human immunodeficiency virus). AZT belongs to a group of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs).

What does AZT stand for?

The drug is usually referred to by its generic name, zidovudine, which is abbreviated to ZDV. The abbreviation AZT is also used, which stands for azidothymidine. Its chemical name is 3'-azido-3'-deoxythymidine.

What are antiretroviral drugs and how do they work?

Antiretroviral drugs HIV is treated with antiretroviral medicines, which work by stopping the virus replicating in the body. This allows the immune system to repair itself and prevent further damage. A combination of HIV drugs is used because HIV can quickly adapt and become resistant.

When was zidovudine discovered?

In November, 1984, zidovudine, first synthesised in 1964, was found to inhibit the replication of animal retroviruses in vitro. Predicting that the drug would be active against HIV, the company applied for a patent.

What is zidovudine made up of?

26 Zidovudine. Zidovudine or azidothymidine (AZT) is azide analog of deoxythymidine; 3′-azido-3′-deoxythymidine. Compounds that are able to block nucleic acid synthesis such as purine and pyrimidine nucleoside analogs are proven antibacterial, antiviral, and anticancer agents.

How many died from AZT?

Although patients using AZT had suffered horribly at first, their survival rate was astonishing. Nineteen people in the placebo group had died versus one in the group receiving AZT. An NIH press release proclaimed that AZT “showed great promise in prolonging life in AIDS patients.

Is AZT still prescribed?

AZT is still one of the most prescribed drugs in the world for HIV treatment due to this heavy use in LMICs.

Why were the initial trials for AZT stopped after only four months?

In 1986, a clinical trial on patients in eight American cities was stopped after four months because AZT seemed to have such dramatic effects on the virus. The next year AZT (Retrovir) became available commercially as the first antiretroviral to be registered by the US Food and Drug Administration (FDA).

Why is zidovudine used in conjunction with other antiretroviral drugs?

Although zidovudine treated an HIV infection, physicians used it together with other antiretroviral medications as of 1996 because when newer, more effective drugs appeared on the market. Scientists referred to that method of treatment as highly active antiretroviral therapy. Using multiple treatments prevented an individual from developing drug resistance. Drug resistance occurs when the body accustoms itself to a drug and is no longer affected by that drug.

When was Zidovudine approved?

In 1985, the Burroughs-Wellcome Fund, a private research foundation in Research Triangle Park, North Carolina, performed a clinical trial that demonstrated zidovudine prolonged the lives of individual humans who had HIV. By the end of 1985, each inhabited region of the world reported at least one case of HIV. The Food and Drug Administration, or FDA, a US organization that promotes public health by monitoring food and drugs headquartered in Silver Spring, Maryland, approved zidovudine after one human clinical trial because no other drug existed to treat the growing population affected by HIV. According to the CDC, from 1987 to 1992, the number of cases of AIDS from progressed HIV grew from 50,280 instances to 202,520 instances in the US. The FDA approved zidovudine to lower those growing numbers of HIV instances. Zidovudine was typically taken as an oral tablet, but professionals could also administer it intravenously in medical situations like during labor and delivery.

What was the first HIV treatment?

Though zidovudine was the first medication to treat HIV, scientists developed several other forms of treatment for HIV. Because of zidovudine, new treatments, and preventative methods, the instances of new HIV diagnoses and rate of maternal-fetal transmission of the virus is generally decreasing each year.

How does Zidovudine affect HIV?

In 1991, researchers in the US tested the efficacy of zidovudine on maternal-fetal transmission of HIV. Pregnant HIV-positive women, or pregnant women who are infected with HIV, can transfer the virus to their fetus in utero. In those cases, the infant would be born HIV-positive. Aside from sexual contact and in utero transmission from pregnant woman to fetus, HIV can be transmitted during breastfeeding or during childbirth through contact with blood. In the 1991 study, researchers showed that zidovudine reduced the rate of maternal-fetal transmission of HIV by two-thirds. In the trial, the researchers gave HIV-positive women 500 mg of zidovudine daily to take orally and then a continuous intravenous drip during labor. The researchers gave newborns oral zidovudine within twenty-four hours of their birth and up to six weeks thereafter. According to the study, the drug was well-tolerated by the pregnant women and did not cause adverse reactions to the infants. On 8 August 1994, the FDA released a statement approving zidovudine to be used to prevent the maternal-fetal transmission of HIV. The zidovudine regimen for HIV-positive pregnant women begins at fourteen weeks gestation and continues into labor, during which they receive an intravenous drip of zidovudine.

What was the cause of AIDS?

On 20 May 1983, researchers Barré-Sinoussi and Montagnier of the Pasteur Institute discovered a retrovirus they named lymphadenopathy associated virus, or LAV, that they thought was the cause of AIDS. In the US, Robert Gallo, a scientist at the NIH, discovered a retrovirus that he named human t-lymphotropic virus type three, or HTLV-III, which he thought caused AIDS. In June 1984, Gallo and Montagnier held a press conference from the Pasteur Institute to announce that LAV and HTLV-III were identical and likely caused AIDS. Both LAV and HTLV-III were the same virus, which was renamed human immunodeficiency virus, or HIV, in 1986.

When did AIDS become transmitted?

On 10 December 1982, the CDC reported that an infant who received a blood transfusion acquired AIDS. In the next week, the CDC reported 22 more cases of immunodeficiency and opportunistic infections in infants. On 7 January 1983, the CDC reported cases of women acquiring AIDS through sexual contact with male partners who had AIDS. Those cases all demonstrated that AIDS could be passed from one human to another, meaning that the condition had to be caused by something transmittable, such as a virus.

How does a retrovirus work?

A retrovirus is a type of virus that attaches to a host cell inside another organism. Many viruses use deoxyribonucleic acid, or DNA, to replicate themselves inside host cells. A retrovirus uses a different type of genetic material called ribonucleic acid, or RNA, to replicate itself. The retrovirus uses reverse transcriptase, an enzyme that facilitates the replication of DNA from the retrovirus’s RNA. Once attached to the host cell, a retrovirus injects its own viral RNA, which is a single-stranded molecule that codes for DNA. DNA is a double-stranded molecule that passes traits from parent to offspring. Once the retrovirus injects its RNA into the host cell, the host cell replicates the retrovirus within itself and spreads the virus to other cells within the body. Those new host cells repeat the process.

What is AZT a class of drugs?

AZT, also referred to as zidovudine, belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors, or NRTIs. The ACTG, established in 1987, quickly began work to build on this discovery.

What did AZT do?

In the laboratory, AZT suppressed HIV replication without damaging normal cells, and the British pharmaceutical company Burroughs Wellcome funded a clinical trial to evaluate the drug in people with AIDS. Used alone, AZT decreased deaths and opportunistic infections, albeit with serious adverse effects. In March 1987, AZT became the first drug ...

When did saquinavir get FDA approval?

In December 1995, saquinavir became the first protease inhibitor to receive FDA approval. In 1996, results from an NIAID-sponsored trial showed that a three-drug regimen of saquinavir, ddC, and AZT was more effective than two-drug therapy with ddC and AZT. One of the key studies demonstrating the efficacy of triple-drug therapy was ACTG 320, ...

Is AZT more effective than AZT alone?

In the early 1990s, data from an NIAID-funded study of AZT in combination with another NRTI drug called dideoxycytidine (ddC), or zalcitabine, showed that this two-drug therapy was more effective than AZT alone, raising hopes about the use of combination therapy in treating HIV/AIDS.

Can HIV evolve rapidly?

HIV variants with mutations that confer resistance to an antiretroviral drug can evolve rapidly. In some people taking AZT alone, drug resistance developed in a matter of days. Scientists thus tested whether combining drugs would make it difficult for the virus to become resistant to all the drugs simultaneously.

What is AZT used for?

In March 1987, AZT became the first drug to gain approval from the U.S. Food and Drug Administration for treating AIDS. AZT, also referred to as zidovudine, belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors, or NRTIs.

When was azidothymidine first used?

Scientists funded by NIH’s National Cancer Institute (NCI) first developed azidothymidine (AZT) in 1964 as a potential cancer therapy. AZT proved ineffective against cancer and was shelved, but in the 1980s, it was included in an NCI screening program to identify drugs to treat HIV/AIDS. In the laboratory, AZT suppressed HIV replication without damaging normal cells, and the British pharmaceutical company Burroughs Wellcome funded a clinical trial to evaluate the drug in people with AIDS. Used alone, AZT decreased deaths and opportunistic infections, albeit with serious adverse effects. In March 1987, AZT became the first drug to gain approval from the U.S. Food and Drug Administration for treating AIDS. AZT, also referred to as zidovudine, belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors, or NRTIs.

When was AZT first used?

AZT, or azidothymidine, was originally developed in the 1960s by a U.S. researcher as way to thwart cancer; the compound was supposed to insert itself into the DNA of a cancer cell and mess with its ability to replicate and produce more tumor cells. But it didn’t work when it was tested in mice and was put aside.

When was the first AIDS drug approved?

Those results — and 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. But the study remains controversial.

Why did Burroughs Wellcome stop the trial?

After 16 weeks, Burroughs Wellcome announced that they were stopping the trial because there was strong evidence that the compound appeared to be working. One group had only one death. Even in that short period, the other group had 19.

How long did it take for the FDA to test for HIV?

But simply having a compound that could work against HIV wasn’t enough. In order to make it available to the estimated millions who were infected, researchers had to be sure that it was safe and that it would indeed stop HIV in some way, even if it didn’t cure people of their infection. At the time, such tests, overseen by the FDA, took eight to 10 years.

How long did it take for HIV to be approved?

That wasn’t always the case. It took seven years after HIV was first discovered before the first drug to fight it was approved by the U.S. Food and Drug Administration (FDA). In those first anxious years of the epidemic, millions were infected.

How many drugs can you take to treat HIV?

T oday, if someone is diagnosed with HIV, he or she can choose among 41 drugs that can treat the disease. And there’s a good chance that with the right combination, given at the right time, the drugs can keep HIV levels so low that the person never gets sick.

Is AIDS a wave?

AIDS was an impending wave that was about to crash on the shores of an unsuspecting — and woefully unprepared — populace. Having at least one drug that worked, in however limited a way, was seen as progress. But even after AZT’s approval, activists and public health officials raised concerns about the price of the drug.

WHAT IS ZIDOVUDINE?

Zidovudine (Retrovir®, AZT) is a drug used for antiretroviral therapy (ART). It was first manufactured by GlaxoSmithKline. Glaxo’s patent on zidovudine expired in 2005. Generic versions made by Aurobindo, Ranbaxy and Roxane were approved in 2005. Zidovudine is also known as azido-deoxythymidine, zidovudine or ZDV.

WHO SHOULD TAKE ZIDOVUDINE?

Zidovudine was approved in 1987 as an antiretroviral (ARV) drug for people with HIV infection. Recommended dosages are available for children over 6 weeks old.

WHAT ABOUT DRUG RESISTANCE?

Many new copies of HIV are mutations. They are slightly different from the original virus. Some mutations can keep multiplying even when you are taking an ARV drug. When this happens, the drug will stop working. This is called “developing resistance” to the drug. See Fact Sheet 126 for more information on resistance.

HOW IS ZIDOVUDINE TAKEN?

The recommended dose of zidovudine for adults is 500mg to 600mg daily. Zidovudine comes in 100mg capsules and 300mg tablets. It is also available in liquid form.

WHAT ARE THE SIDE EFFECTS?

When you start ART, you may have temporary side effects such as headaches, high blood pressure, or a general sense of feeling ill. These side effects usually get better or disappear over time. Some patients taking zidovudine continue to have nausea, vomiting, headaches and fatigue.

HOW DOES ZIDOVUDINE REACT WITH OTHER DRUGS?

Zidovudine can interact with other drugs or supplements you are taking. These interactions can change the amount of each drug in your bloodstream and cause an under- or overdose. New interactions are constantly being identified. Make sure that your health care provider knows about ALL drugs and supplements you are taking.

How many antiretroviral products are there?

This article introduces a special issue of Antiviral Researchfocusing on progress against HIV-1 and prospects for the future. Physicians now have approximately thirty antiretroviral products, formulated either singly or in combination, to treat patients with human immunodeficiency virus (HIV-1), the pathogenic retrovirus which causes the acquired immunodeficiency syndrome (AIDS) and related conditions (Table 1). Most are oral medicines, administered on convenient schedules. Several have been specially formulated as fixed-dose, generic-drug combinations for even greater utility in resource-poor nations.

What was the first NRTI?

1Zidovudine (AZT) was the first NRTI to be administered to patients with HIV-1 infection and the first antiretroviral drug to be approved. It is still in use in combination products.

Is AZT a cancer drug?

With grant support from the NCI, AZT is first synthesized as a potential anti-cancer agent.

Was AIDS caused by a retrovirus?

There can be no doubt that the rapid application of this knowledge saved countless lives. However, the realization that a retrovirus was the cause of AIDS revived a sense of futility or therapeutic nihilism in many clinical researchers and patients alike. The belief that retroviruses were, by definition, not amenable to therapy remained strong, to the potential detriment of clinical research by creating a self-imposed restriction on what the available clinical science and technology could accomplish, or possibly even try.

Is Zalcitabine a DDC?

zalcitabine, dide oxycytidine, ddC (no longer marked as of December 31, 2006)

Does AZT inhibit HIV?

AZT shown to act through its triphosphate to inhibit the HIV RT.

Does AZT affect HIV replication?

Testing at NCI shows that AZT suppresses HIV-1 replication of diverse strains in vitroat doses that do not damage viability and function of normal cells.

How does AZT work?

Sold under the brand name Retrovir, AZT works by blocking proteins called enzymes that the virus needs to replicate itself. The FDA approved AZT in less than 4 months, fast-tracking a process that usually takes many years.

How long does it take for AZT to be approved?

The FDA approved AZT in less than 4 months, fast-tracking a process that usually takes many years. It treats HIV, but it isn’t a cure.

What was the name of the disease that destroyed the immune system and left the body open to all kinds of infections?

Others were coming down with a rare type of pneumonia. A year later, the mysterious disease had a name: acquired immune deficiency syndrome , or AIDS. It destroyed the immune system and left the body open to all kinds of infections. In 1983, scientists discovered the virus that causes AIDS.

How many HIV medications are there?

Today, more than 30 HIV medications are available. Many people are able to control their HIV with just one pill a day. Early treatment with antiretrovirals can prevent HIV-positive people from getting AIDS and the diseases it causes, like cancer.

What drug was approved in 2012?

A study showed that taking a daily dose of antiretrovirals not only helped those who were HIV-positive, but also could protect healthy people from becoming infected. In 2012, the FDA approved the drug Truvada for pre-exposure prophylaxis, or PrEP.

When did the FDA approve the pill Combivir?

The multiple doses and the drugs’ side effects drove many people to quit their HIV therapy. Then in 1997 , the FDA approved a pill called Combivir that contained two anti-HIV drugs and was easier to take. Nearly 2 decades after the emergence of HIV and AIDS, a dozen antiretroviral drugs were on the market. PrEP.

What is the name of the drug that is used to treat HIV/AIDS?

These drugs paved the way to a new era of combination therapy for HIV/AIDS. Doctors began prescribing saquinavir plus AZT or other antiretrovirals. This combination therapy was dubbed highly active antiretroviral therapy (HAART). That approach became the new standard of care for HIV in 1996. HAART greatly lengthened the life span of people with AIDS.

What is AZT treatment?

AZT served has since been called the “prototype” for AIDS treatment and is considered a “first step” in the AIDS response, establishing standards and an understanding of viral suppression.

What was the first drug approved by the FDA to treat AIDS?

AZT was the first drug approved by the FDA to treat AIDS. Public Domain

How many deaths were caused by AZT?

It is unknown how many — if any — deaths resulted directly from patients being treated with AZT, as early testing was not always standardized to account for various other experimental and approved treatments, as well as from infection by HIV or other secondary illnesses.

How many drugs are there for AIDS in 2021?

In 2021, there are more than 30 drugs designed to block viral replication at different stages of its life cycle — one such being Retrovir, the market name for AZT. A CDC report analyzing reported AIDS cases from the first reported case in the U.S. in June 1981 to Dec. 31, 2000, showed that 774,467 people had been diagnosed with AIDS in the U.S. Of those, 448,060 had died.

Did Magic Johnson use AZT?

Throughout the early 1990s, additional NRTI drugs gained approval, showing that along with AZT, other therapeutic drugs were effective at treating AIDS. In 1991, an asymptomatic Magic Johnson made headlines when the basketball legend began a treatment of AZT following a recent AIDS diagnosis, The Washington Post reported at the time. In an interview with CNN nearly three decades later, Johnson credited his early intervention and quick course of treatment with following scientific recommendations.

Does AZT reduce side effects?

That same year, clinical trial ACTG 016 established that a lower therapeutic dose of AZT reduced some side effects. The subsequent ACTG 019 trial showed that the drug could delay the onset of AIDS in asymptomatic people with HIV.

Does AZT affect replication?

In February 1985, Broder would later write that testing showed AZT suppresses HIV replication in culture dishes and did not damage the viability and function of normal cells. When used alone, AZT was found to decrease death and opportunistic infections in AIDS patients. By July, the first patients would be enrolled in the AZT Phase I trial; a Phase II randomized, placebo-controlled study of AZT efficacy in AIDS patients would begin in February of the next year (more on that controversial study later).

AZT: The First Drug to Treat HIV Infection

• Scientists funded by NIH’s National Cancer Institute (NCI) first developed azidothymidine (AZT) in 1964 as a potential cancer therapy. AZT proved ineffective against cancer and was shelved, but in the 1980s, it was included in an NCI screening program to identify drugs to treat HIV/AIDS. In the laboratory, AZT suppressed HIV replication without dam...

See more on niaid.nih.gov

Accelerating Antiretroviral Drug Development

The Advent of Combination Therapy

Durable HIV Suppression with Triple-Drug Therapy

Identifying New Classes of Antiretroviral Drugs