Understanding What Are the Side Effects of AZT (Zidovudine)

October 9, 2025 •

4 min read

In 1987, the FDA approved zidovudine (AZT), marking the first antiretroviral drug for HIV/AIDS treatment. While a significant medical breakthrough at the time, its early use was associated with substantial toxicity, leading many to question what are the side effects of AZT. Early formulations and dosages led to frequent and sometimes severe adverse reactions, though modern treatment strategies have significantly improved its tolerability.

Quick Summary

A guide detailing the side effects of AZT, or zidovudine. It examines common adverse reactions like gastrointestinal distress and headaches, as well as significant toxicities involving bone marrow suppression (anemia, neutropenia), liver issues, and mitochondrial problems leading to myopathy and lactic acidosis. The article also covers risk factors and contemporary management approaches.

Key Points

Hematologic Toxicity: AZT is known to cause bone marrow suppression, leading to significant anemia and neutropenia, which can be severe and require dose changes or transfusions.
Mitochondrial Damage: A major long-term risk of AZT is mitochondrial toxicity, which can manifest as myopathy (muscle weakness) and, rarely, life-threatening lactic acidosis and liver problems.
Gastrointestinal Distress: Nausea, vomiting, and abdominal pain are very common, especially during the initial weeks of therapy.
Neurological Symptoms: Headaches, insomnia, and general malaise are frequently reported side effects that often improve with continued treatment.
Fat Redistribution: Prolonged use of AZT, particularly in older regimens, was associated with lipoatrophy, a visible loss of subcutaneous fat in certain body areas.
Risk Mitigation: Side effects are less common and severe with modern, lower-dose AZT regimens and combination therapy. Close medical monitoring is crucial for early detection and management.
Improved Alternatives: Due to its toxicities, AZT is less of a first-line therapy today, with newer, more tolerable drugs often preferred.

A Retrospective on AZT in HIV Treatment

Zidovudine (AZT) was a pioneering medication in the fight against HIV, offering the first real hope for treatment and prolonging the lives of those infected. As a nucleoside analog reverse transcriptase inhibitor (NRTI), it works by interfering with HIV's replication process. However, the initial high-dose regimens, such as 400 mg every four hours, were linked with a high incidence of adverse effects. As combination therapies (HAART) and lower-dose regimens became standard, the overall toxicity profile of AZT improved significantly. Nonetheless, a thorough understanding of its potential side effects remains crucial for both historical context and current clinical practice.

Common Side Effects of AZT

Many patients beginning AZT therapy reported a range of less severe, yet bothersome, side effects. These reactions often improved or resolved over the first several weeks of treatment.

Gastrointestinal Intolerance: A significant portion of patients experienced nausea, vomiting, abdominal pain, and diarrhea. This was particularly noted with early, higher-dose regimens.
Headaches: Severe headaches were a frequent complaint, especially early in treatment.
Malaise and Fatigue: Feelings of general discomfort, unusual tiredness, and lack of energy were commonly reported by patients.
Insomnia: Difficulty falling or staying asleep was another documented side effect.
Myalgia: Muscle pain and soreness were relatively common.

Serious and Long-Term Side Effects

While the more common side effects are manageable, AZT is known for more serious toxicities, particularly with long-term use. These often result from the drug's effect on cellular processes, including mitochondrial function and bone marrow activity.

Hematologic Toxicity (Bone Marrow Suppression)

One of the most notable and serious side effects of AZT is its toxicity to bone marrow, where blood cells are produced. This can lead to potentially life-threatening blood disorders.

Anemia: Severe anemia, or a very low red blood cell count, was a common occurrence, particularly in patients with advanced HIV disease. The risk was higher in individuals with lower baseline hemoglobin levels.
Neutropenia: This condition involves an abnormally low count of neutrophils, a type of white blood cell essential for fighting infection. Neutropenia was more likely to occur after several months of treatment.
Management: Due to these risks, close monitoring of blood cell counts (Complete Blood Count or CBC) is essential for patients on AZT. Management can involve dose reduction, temporary interruption of therapy, or in severe cases, the use of stimulating factors or blood transfusions.

Mitochondrial and Muscular Toxicity

AZT can inhibit a DNA polymerase enzyme critical for mitochondrial function, leading to various forms of cellular damage, especially in muscle and liver tissue.

Myopathy: Prolonged use of AZT is associated with muscle weakness and wasting (myopathy). This can cause muscle pain, tenderness, and noticeable loss of muscle mass, particularly in the limbs.
Lactic Acidosis and Hepatic Steatosis: A rare but life-threatening complication is lactic acidosis, a buildup of lactic acid in the blood. This can be accompanied by hepatic steatosis (excess fat in the liver) and cause symptoms like extreme tiredness, shortness of breath, and abdominal pain.

Other Significant Side Effects

Lipoatrophy: Long-term AZT use has been linked to lipoatrophy, a loss of subcutaneous fat in areas like the face, arms, and legs. This fat wasting contributed to the physical stigma of HIV treatment in earlier years but is less common with modern regimens.
Hepatotoxicity: Liver problems, including elevated liver enzymes and severe liver enlargement with steatosis (hepatomegaly), have been reported. Liver function tests are monitored regularly during treatment.

Risk Factors and Management

Several factors can increase a patient's risk of experiencing adverse effects from AZT. These include pre-existing conditions and the concurrent use of other medications. Regular monitoring is key to mitigating these risks.

Comparison of AZT Side Effects with Modern Antiretrovirals

The landscape of HIV treatment has evolved dramatically since AZT was first introduced. Modern antiretroviral drugs generally have more favorable side effect profiles.


Feature	AZT (Zidovudine)	Modern NRTIs (e.g., Tenofovir/Emtricitabine)
Toxicity Profile	High incidence of bone marrow suppression, mitochondrial toxicity	Generally lower risk of severe bone marrow and mitochondrial toxicity
Common Side Effects	Nausea, headaches, GI distress, fatigue, insomnia	Generally well-tolerated; some GI upset or headaches possible early on
Serious Risks	Severe anemia, neutropenia, myopathy, lactic acidosis, lipoatrophy	Rare risk of lactic acidosis; different long-term issues like renal toxicity with tenofovir
Dosing Frequency	Historically dosed frequently (multiple times per day); modern dosing is often twice daily	Often combined into a single pill, once-daily regimen
Drug-Drug Interactions	Potential interactions can increase toxicity (e.g., ribavirin, ganciclovir)	Fewer clinically significant interactions with many modern combinations

Mitigating AZT Side Effects

Monitor and adjust: Close monitoring through regular blood tests is critical. If significant bone marrow suppression occurs, dosage adjustments or a switch to an alternative antiretroviral may be necessary.
Treat symptomatically: Common side effects like nausea or headaches are often treated with symptomatic relief, and many improve over time.
Address deficiencies: Low levels of folic acid or vitamin B12 can worsen anemia caused by AZT and should be addressed.
Alternative regimens: In cases of serious or intractable side effects, changing the antiretroviral regimen is the primary strategy. The development of newer, less toxic drugs has provided more options. For more detailed information on HIV medication side effects, see the HIVinfo fact sheet on HIV Medicines and Side Effects.

Conclusion

AZT's discovery represented a monumental step forward in HIV treatment, but the experience of patients on early, high-dose regimens highlighted a challenging array of side effects. Common issues like gastrointestinal upset and headaches are usually manageable, but more severe toxicities such as bone marrow suppression, myopathy, and lactic acidosis can necessitate changes in treatment. The evolution of antiretroviral therapy has led to far more tolerable and effective drug combinations, relegating AZT to a more limited role today. However, the history of what are the side effects of AZT serves as an important lesson in pharmacology, demonstrating the balance between a drug's therapeutic benefits and its potential for harm, underscoring the ongoing need for vigilant patient monitoring.

Frequently Asked Questions

The most common serious side effects of AZT are hematologic toxicities, including anemia and neutropenia, which result from bone marrow suppression.

Yes, prolonged use of AZT can cause myopathy, a condition characterized by muscle pain, tenderness, and weakness, resulting from mitochondrial damage.

When starting AZT, common early side effects include headaches, nausea, vomiting, malaise, and insomnia. These often lessen or disappear after a few weeks.

Lactic acidosis is a rare but serious buildup of lactic acid in the blood. It is a potential side effect of AZT and other nucleoside analog medications, stemming from mitochondrial toxicity.

AZT-induced anemia is managed through regular blood count monitoring. Treatment may involve dose reduction, discontinuing AZT, or administering medications like erythropoietin to stimulate red blood cell production.

While AZT was a cornerstone of early HIV treatment, its use today is less common due to significant side effects and the availability of newer, more tolerable, and effective antiretroviral agents.

Lipoatrophy is the loss of subcutaneous fat, particularly in the face, arms, and legs. Prolonged AZT use, especially with older, higher-dose regimens, has been associated with this condition.