Zidovudine (Retrovir) AZT - ZDV 💊
Always check the BNF entry for Zidovudine (AZT) for up-to-date guidance.
- Zidovudine (AZT) is an antiviral agent used in the treatment and prevention of HIV/AIDS.
- It was the first antiretroviral approved for HIV and remains in use as part of combination therapy (HAART).
- It can also reduce maternal–fetal transmission of HIV when used during pregnancy and labour.
⚙️ Mode of Action
- Zidovudine is a thymidine analogue belonging to the nucleoside reverse-transcriptase inhibitor (NRTI) class.
- It is phosphorylated intracellularly to its active triphosphate form, which competitively inhibits HIV reverse transcriptase.
- Incorporation into viral DNA causes premature chain termination, halting viral replication.
📋 Indications
- Part of HAART (Highly Active Antiretroviral Therapy) for HIV infection.
- Prevention of mother-to-child transmission of HIV during pregnancy, labour, and postpartum.
- May be used in certain post-exposure prophylaxis (PEP) regimens.
💊 Dose
- HIV infection: Zidovudine 300 mg twice daily (no food restrictions).
- Prevention of transmission in pregnancy: Typically started after 14 weeks’ gestation under specialist supervision.
- Renal impairment: Dose reduction is required; consult renal dosing tables or BNF.
🤝 Interactions
- Stavudine (d4T): Avoid concurrent use-antagonistic effect.
- Doxorubicin / Ribavirin: Avoid combination due to additive myelotoxicity.
- Bone-marrow suppressive or cytotoxic agents: May potentiate anaemia or neutropenia.
- Renal failure or dialysis: Requires dose adjustment and close haematological monitoring.
🚫 Contraindications / Cautions
- Not initiated before 14 weeks’ gestation unless benefit outweighs risk.
- Use cautiously in patients with pre-existing anaemia or neutropenia.
- Monitor liver function and lactate in long-term therapy.
⚠️ Side Effects
- 💢 Common: Nausea, vomiting, headache, dizziness, myalgia, fatigue.
- 🩸 Haematological: Anaemia, neutropenia, pancytopenia, and bone-marrow suppression (dose-related).
- 🫀 Metabolic: Lactic acidosis with hepatic steatosis - a class effect of NRTIs.
- 💪 Muscular: Myopathy and muscle weakness due to mitochondrial toxicity.
- 🧠 Neurotoxicity: Occasionally causes insomnia or paraesthesia.
- 🧪 Liver: Transient transaminase elevation, rarely hepatitis.
🧠 Teaching Commentary
- Zidovudine’s structural mimicry of thymidine underlies both its efficacy and toxicity-it impairs viral reverse transcriptase but also human mitochondrial DNA polymerase.
- Haematological toxicity is dose-limiting; hence AZT is often replaced by less myelotoxic NRTIs such as tenofovir or abacavir in modern regimens.
- Nevertheless, its historical role is pivotal-it transformed HIV from a fatal illness into a chronic manageable condition.
- In pregnancy, it remains part of some UK perinatal HIV protocols (see BHIVA guidelines).
📚 References
- Zidovudine – BNF
- British HIV Association (BHIVA) Guidelines for the Management of HIV in Pregnancy, 2024.
- Nelson MR, et al. HIV Medicine (2023 update).
- Oxford Handbook of Infectious Diseases and Microbiology, 3rd ed.
