Makindo Medical Notes

⚠️ Warning: Stavudine (d4T) is rarely used in current UK HIV practice due to its high toxicity profile, including lactic acidosis, peripheral neuropathy, and lipodystrophy. Use only under specialist supervision when no safer alternatives are available.

🧠 About

• Stavudine (d4T) is a nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of HIV-1 infection.
• It is now largely obsolete in the UK and most global guidelines due to long-term mitochondrial toxicity and availability of safer NRTIs such as tenofovir and lamivudine.
• Always check the BNF entry for Stavudine before prescribing.

⚙️ Mode of Action

• Stavudine is a thymidine analogue that inhibits HIV reverse transcriptase after intracellular phosphorylation to its active triphosphate form.
• It competes with thymidine triphosphate for incorporation into viral DNA, causing chain termination and blocking viral replication.
• It also inhibits mitochondrial DNA polymerase γ, leading to mitochondrial dysfunction — the root cause of its toxicities (e.g. lactic acidosis, neuropathy, and lipodystrophy).

💊 Indications & Dose

• Dose should be reduced in renal impairment or low body weight (<60 kg).
• Administer as part of combination antiretroviral therapy (cART) — never as monotherapy due to rapid resistance.

⚠️ Interactions

• Avoid combination with didanosine (ddI) or zidovudine (AZT) — additive mitochondrial toxicity and antagonistic antiviral effects.
• See BNF for a full list of drug–drug interactions, especially those affecting renal clearance or mitochondrial metabolism.

⚕️ Cautions

• Monitor for early signs of lactic acidosis (nausea, abdominal pain, breathlessness).
• Use with caution in hepatic impairment or obesity (increased risk of fatty liver and lactic acidosis).
• Stop treatment immediately if peripheral neuropathy or pancreatitis develops.

🚫 Contraindications

• History of lactic acidosis or severe hepatomegaly with steatosis.
• Significant neuropathy or pancreatitis.
• Severe renal impairment (dose adjustment required under specialist care).

💥 Side Effects

• Very common: Peripheral neuropathy (dose-related and may be irreversible).
• Common: Nausea, diarrhoea, rash, fatigue.
• Serious: Lactic acidosis, hepatic steatosis, pancreatitis, lipodystrophy, and dyslipidaemia.
• Long-term use associated with fat redistribution (“buffalo hump”, central obesity) and insulin resistance.

📖 Educational Summary

Stavudine was one of the early NRTIs that revolutionised HIV care in the 1990s but fell out of use due to its mitochondrial toxicity. It serves as a classic example of how NRTIs can cause systemic effects by interfering with host mitochondrial DNA synthesis — explaining lactic acidosis, myopathy, and hepatic steatosis. Modern practice has replaced stavudine with agents like tenofovir disoproxil and abacavir, which maintain efficacy with less toxicity. For learners, it illustrates the principle that antiretroviral potency must always be balanced against long-term metabolic safety.

📚 References

• Stavudine – British National Formulary
• BHIVA Guidelines for HIV Treatment (2023)
• WHO Consolidated Guidelines on HIV Treatment (2023 Update)
• Harrison’s Principles of Internal Medicine, 21st Edition – HIV Pharmacology