Zidovudine is an antiviral medication used to treat HIV-1 infection. It was the first drug ever approved to treat AIDS, receiving FDA approval in March 1987. Also known by its abbreviation AZT and the brand name Retrovir, zidovudine belongs to a class of drugs called nucleoside analog reverse transcriptase inhibitors (NRTIs). It remains in use today, primarily in combination with other antiretroviral drugs and as a key tool for preventing HIV transmission from mother to baby during pregnancy and birth.
How Zidovudine Works
HIV replicates by hijacking a cell’s machinery to copy its own genetic material. A viral enzyme called reverse transcriptase reads the virus’s RNA and builds a new strand of DNA from it, using the cell’s natural building blocks (nucleotides). Zidovudine is a mimic of one of those building blocks, thymidine. It looks close enough to the real thing that reverse transcriptase grabs it and inserts it into the growing DNA chain.
The difference is a small chemical modification: where thymidine has a specific attachment point that lets the next building block link on, zidovudine has a different chemical group that blocks that connection entirely. Once zidovudine gets incorporated, the DNA chain hits a dead end and can’t grow any further. This “chain termination” stops the virus from completing its DNA copy and, in turn, from producing new viral particles.
Zidovudine is actually a prodrug, meaning it’s inactive when you swallow it. Inside your cells, enzymes add phosphate groups to it in three steps, converting it into its active form. Only then can it compete with the natural thymidine building block for a spot in the viral DNA strand.
What Zidovudine Is Used For
Zidovudine has two FDA-approved uses. The first is treating HIV-1 infection in combination with other antiretroviral medications. It is not used alone for treatment because HIV can quickly develop resistance to a single drug. Modern HIV therapy pairs it with at least one or two other antiretrovirals to attack the virus from multiple angles simultaneously.
The second approved use is preventing mother-to-child HIV transmission. This protocol has three phases: the mother takes zidovudine during pregnancy, receives it intravenously during labor, and the newborn receives it after birth. This approach dramatically reduces the chance of the baby contracting HIV. Intravenous zidovudine during labor is especially recommended when the mother’s viral load is unknown or elevated near delivery.
Standard Dosing
For adults treating HIV, the typical oral dose is 300 milligrams taken twice a day, always alongside other antiretroviral medications. It’s available as tablets, capsules, and an oral solution. The drug can be taken with or without food. Pregnant individuals take the same standard adult dose, since pregnancy does not significantly change how the body processes zidovudine.
The drug has a short plasma half-life of roughly one hour. Your liver breaks it down primarily through a process called glucuronidation, and the resulting metabolite is then excreted through the kidneys. Because of this pathway, people with significant liver or kidney problems may process the drug differently and could need monitoring.
Side Effects
The most serious concern with zidovudine is its effect on the bone marrow, which produces blood cells. It can suppress bone marrow activity, leading to anemia (low red blood cells) or neutropenia (low white blood cells called neutrophils). This risk is higher at larger doses and in people whose bone marrow is already compromised. Regular blood count monitoring is a standard part of treatment.
Other potential side effects include headache, nausea, fatigue, and muscle pain. Like other drugs in its class, zidovudine carries a risk of a rare but serious condition involving the buildup of lactic acid in the blood, sometimes accompanied by liver enlargement. Symptoms like persistent nausea, abdominal pain, or unusual fatigue can be warning signs of this complication.
Drug Interactions to Know About
Zidovudine should not be taken alongside stavudine, another NRTI. Despite both targeting the same viral enzyme, they actually work against each other. Studies have shown an antagonistic relationship where the two drugs cancel out each other’s antiviral effects rather than boosting them.
Ribavirin, a drug used to treat hepatitis C, also interferes with zidovudine’s ability to fight HIV and can increase the risk of blood-related side effects. The chemotherapy drug doxorubicin similarly antagonizes zidovudine and should not be combined with it. More broadly, any medication that suppresses bone marrow, including ganciclovir and interferon alfa, can compound zidovudine’s own bone marrow toxicity.
Its Place in HIV Treatment Today
When zidovudine was approved in 1987, it was a lifeline for people with AIDS at a time when no antiviral treatments existed. Early on, it was given at high doses as a single agent, which led to significant toxicity and rapid drug resistance. The development of combination therapy in the mid-1990s transformed HIV treatment, and zidovudine became one piece of a multi-drug regimen rather than a standalone treatment.
Newer antiretroviral drugs with fewer side effects and more convenient dosing schedules have largely replaced zidovudine as a first-line treatment in high-income countries. However, it remains an important option in certain situations, particularly for preventing mother-to-child transmission, where it has one of the longest and strongest evidence bases of any antiretroviral. It also still appears in treatment guidelines as an alternative regimen when preferred drugs aren’t suitable due to resistance, intolerance, or availability. In many parts of the world, zidovudine continues to be a cornerstone of accessible HIV care.