Zidovudine

Introduction

Zidovudine (also known as AZT, ZDV, and by its trade name Retrovir) is an antiretroviral medication used to prevent and treat HIV/AIDS. It is typically used in combination with other antiretrovirals and is a key component of highly active antiretroviral therapy (HAART). Zidovudine was the first drug approved for the treatment of HIV and has played a significant role in the management of the disease.

History

Zidovudine was initially synthesized in 1964 by Jerome Horwitz as a potential anticancer drug. However, it was not until the mid-1980s that its efficacy against HIV was discovered. The drug was approved by the U.S. Food and Drug Administration (FDA) in 1987, making it the first antiretroviral drug available for the treatment of HIV/AIDS.

Mechanism of Action

Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI). It works by inhibiting the activity of reverse transcriptase, an enzyme crucial for the replication of HIV. By incorporating itself into the viral DNA, zidovudine terminates the DNA chain, preventing the virus from multiplying.

Pharmacokinetics

Zidovudine is well-absorbed from the gastrointestinal tract, with bioavailability ranging from 60% to 70%. It is metabolized primarily in the liver to its active form, zidovudine triphosphate. The drug has a half-life of approximately one hour, necessitating frequent dosing. Zidovudine and its metabolites are excreted primarily through the kidneys.

Clinical Use

HIV Treatment

Zidovudine is used in combination with other antiretroviral drugs to treat HIV infection. It is particularly effective in reducing the viral load and increasing CD4 cell counts, thereby improving immune function and reducing the risk of opportunistic infections.

Prevention of Mother-to-Child Transmission

Zidovudine is also used to prevent mother-to-child transmission of HIV during childbirth. Administering the drug to HIV-positive pregnant women and their newborns significantly reduces the risk of transmission.

Post-Exposure Prophylaxis

In cases of potential HIV exposure, zidovudine is used as part of post-exposure prophylaxis (PEP) to reduce the likelihood of infection. This is particularly relevant for healthcare workers who may be exposed to HIV through needlestick injuries.

Side Effects

Common side effects of zidovudine include anemia, neutropenia, and gastrointestinal disturbances such as nausea and vomiting. Long-term use can lead to more severe complications, including myopathy and lactic acidosis. Regular monitoring of blood counts and liver function tests is recommended for patients on zidovudine therapy.

Resistance

HIV can develop resistance to zidovudine through mutations in the reverse transcriptase enzyme. Resistance is often associated with prolonged monotherapy, underscoring the importance of combination therapy to maintain efficacy.

Drug Interactions

Zidovudine can interact with other medications, potentially altering its effectiveness or increasing the risk of side effects. Notable interactions include those with ganciclovir, ribavirin, and certain antineoplastic agents. Clinicians should carefully review a patient's medication regimen to avoid adverse interactions.

Formulations and Dosage

Zidovudine is available in various formulations, including oral tablets, capsules, and an intravenous solution. The standard adult dosage is 300 mg twice daily, although dosing may vary based on specific clinical scenarios, such as during pregnancy or in pediatric patients.

Research and Development

Ongoing research aims to improve the efficacy and safety profile of zidovudine. Studies are exploring new combination therapies, dosing strategies, and the development of resistance. Additionally, research into the long-term effects of zidovudine continues to inform clinical practice.

References