HIV Distal Symmetric Polyneuropathy

HIV distal symmetric polyneuropathy is the commonest neurological complication of HIV, affecting 30 to 60% of people with HIV, with painful sensory symptoms in many. It arises from HIV itself and from neurotoxic antiretroviral drugs (stavudine, didanosine, zalcitabine), which are now rarely used.

Pathophysiology. Macrophage activation and inflammatory cytokine release cause length dependent axonal degeneration of small and large fibres. Mitochondrial toxicity from older nucleoside drugs and comorbid diabetes, alcohol, B12 deficiency and isoniazid add to injury.

Burning pain, numbness, paraesthesia and allodynia in the feet, ascending to the legs and hands. Ankle reflexes are lost, with reduced pinprick and vibration sense in a stocking distribution. Weakness is mild and distal. Autonomic symptoms may occur.

Diagnosis is clinical. Nerve conduction studies show axonal sensory loss (may be normal in small fibre disease). Skin biopsy shows reduced intraepidermal nerve fibre density. Check HIV viral load and CD4 count, glucose, vitamin B12, thyroid function, renal function and alcohol use. Review drug history.

Differential diagnosis.

• Neuropathy from diabetes, vitamin B12 or folate deficiency, alcohol and thyroid disease.
• CMV polyradiculopathy, inflammatory neuropathy and mononeuritis multiplex.
• Syphilis, hepatitis C neuropathy and isoniazid or dapsone toxicity.
• Leprosy in endemic regions.

Treat the cause. Start or optimise antiretroviral therapy, avoid and replace stavudine, didanosine and zalcitabine, and correct deficiencies.

Neuropathic pain.

• Gabapentin 300 mg at night, increased to 600 to 1200 mg three times daily (adjust to eGFR), or pregabalin 75 mg twice daily, increased to 300 mg twice daily.
• Amitriptyline 10 mg at night, increased to 25 to 75 mg (caution in older adults, avoid in cardiac conduction disease), or duloxetine 30 mg daily, increased to 60 mg.
• Topical capsaicin 8% patch (up to 4 patches for 30 minutes on feet, repeated every 3 months) or lidocaine 5% plaster for localised pain.
• Avoid tramadol and opioids unless needed, owing to interactions and dependence. Smoked cannabis has been studied but is not advised.

Non-drug measures. Foot care, well fitting footwear, and falls prevention.

Monitoring. Pain scores, foot examination at each visit, B12 and glucose.

Referral and escalation. Refer to neurology for atypical, asymmetric, rapidly progressive or motor predominant disease.

Special groups. In pregnancy, avoid duloxetine and discuss gabapentinoids with obstetrics.