zidovudine

zidovudine, also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals and was the first treatment approved for the infection. This nucleoside analog reverse transcriptase inhibitor is a cornerstone of antiretroviral therapy and is also used to prevent mother-to-child transmission during birth.

Medical uses

Zidovudine is indicated as part of combination therapy for the treatment of human immunodeficiency virus infection. It is a key component in many first-line regimens, often paired with agents like lamivudine. For the prevention of perinatal transmission, it is administered to the mother during pregnancy and labor and to the newborn after delivery. It may also be used as part of post-exposure prophylaxis following a significant exposure to HIV-contaminated material, such as a needlestick injury in a healthcare setting. The medication is effective at reducing the viral load and increasing CD4 count in infected individuals.

Adverse effects

Common adverse effects include nausea, headache, fever, and general malaise. A significant side effect is bone marrow suppression, which can lead to anemia and neutropenia, requiring regular monitoring of blood counts. Myopathy, characterized by muscle pain and weakness, and lactic acidosis, a serious metabolic condition, are associated with long-term use. Lipodystrophy, involving changes in body fat distribution, has been observed with many antiretrovirals, including this drug. Early use at high doses was also linked to severe hepatotoxicity.

Pharmacology

As a nucleoside analog reverse transcriptase inhibitor, it is phosphorylated intracellularly to its active triphosphate form. This metabolite competitively inhibits the incorporation of thymidine triphosphate into viral DNA by the enzyme reverse transcriptase, thereby terminating the growing DNA chain. It is primarily metabolized by glucuronidation in the liver via the UGT2B7 enzyme. The drug has good oral bioavailability and crosses the blood–brain barrier, which is important for treating HIV-associated neurocognitive disorders. Its plasma half-life is about 1 hour, while the intracellular half-life of the active form is longer.

History

The compound was first synthesized in 1964 by Jerome P. Horwitz at the Michigan Cancer Foundation as a potential cancer drug, but it was shelved. In the 1980s, during the emerging AIDS epidemic, researchers at the National Cancer Institute, including Samuel Broder and Hiroaki Mitsuya, screened compounds for activity against HIV. Burroughs Wellcome (now part of GlaxoSmithKline) scientists, notably Janet Rideout, contributed to its development. Following promising clinical trials, it was rapidly approved by the U.S. Food and Drug Administration in 1987, marking the first approval of an antiretroviral. The high cost and accessibility of the drug later became central to activism by groups like ACT UP.

Society and culture

The approval and pricing of zidovudine were major points of controversy during the AIDS crisis, sparking widespread protests by AIDS activists demanding equitable access. It is on the World Health Organization's List of Essential Medicines. The drug has been the subject of numerous legal and ethical debates concerning patent law and drug affordability in the developing world. Its development story is featured in the play and film The Normal Heart and the documentary How to Survive a Plague. The brand name Retrovir is owned by ViiV Healthcare.

Category:Antiviral drugs Category:World Health Organization essential medicines Category:HIV/AIDS