Can Human Immunodeficiency Virus (HIV) cause extremity weakness?

HIV and Extremity Weakness

Yes, HIV can cause extremity weakness through several neurological mechanisms, most commonly through peripheral neuropathy which affects 13-50% of people living with HIV (PLWH). 1

Primary Mechanisms of HIV-Related Extremity Weakness

1. HIV-Associated Peripheral Neuropathies

• Distal Symmetrical Polyneuropathy (DSP)
  • Most common form of neuropathy in HIV patients 1, 2
  • Presents as "cold burning pain" in a glove-and-stocking distribution 1
  • Starts distally with lower extremities more affected than upper extremities
  • Features include painful response to light touch (allodynia) 1
  • Caused by:
    • Direct HIV infection effects
    • Antiretroviral therapy (ART) toxicity, particularly older nucleoside analogues (stavudine, didanosine, zalcitabine) 1

2. Other HIV-Related Neuropathies Causing Weakness

• Inflammatory Demyelinating Polyneuropathies 3, 4

  • Occur in early, asymptomatic HIV infection
  • Characterized primarily by muscle weakness rather than sensory symptoms
  • Include both acute (AIDP) and chronic (CIDP) forms 2

• Progressive Polyradiculopathy 1, 4

  • Occurs in advanced HIV disease with low CD4 counts
  • Rapidly progressive weakness if untreated
  • Often associated with cytomegalovirus infection

• Mononeuropathies and Multiple Mononeuropathies 1, 4

  • Single or multiple nerve involvement
  • Multiple mononeuropathies often occur with CD4 counts <50
  • May be associated with cytomegalovirus infection

3. HIV-Associated Myopathy 3

• Not associated with any particular stage of immunosuppression
• Presents with symmetrical weakness of proximal muscles
• Often shows moderately elevated serum creatine kinase levels
• Diagnosis confirmed by electromyography and muscle biopsy

Diagnostic Approach for HIV-Related Extremity Weakness

1. Assess pattern of weakness:

   • Distal vs. proximal
   • Symmetrical vs. asymmetrical
   • Upper vs. lower extremity predominance

2. Evaluate for associated symptoms:

   • Pain characteristics (burning, electric, deep)
   • Sensory changes (numbness, tingling)
   • Autonomic symptoms

3. Consider CD4 count and disease stage:

   • Higher CD4: Inflammatory demyelinating neuropathies more common
   • Lower CD4: Opportunistic infection-related neuropathies more likely 2

4. Review medication history:

   • Antiretroviral medications, particularly older nucleoside analogues
   • Other potentially neurotoxic medications

Management Considerations

1. For distal symmetrical polyneuropathy:

   • Consider modifying ART regimen if medication toxicity is suspected 2
   • First-line treatments for neuropathic pain (pregabalin, gabapentin) have limited efficacy 5
   • Topical capsaicin may be considered despite side effects 2

2. For inflammatory demyelinating polyneuropathies:

   • May respond to plasmapheresis or steroids 4

3. For progressive polyradiculopathy or CMV-related neuropathies:

   • Requires prompt, aggressive treatment of underlying infection 4

4. For HIV myopathy:

   • Treatment options include corticosteroids, NSAIDs, and intravenous immunoglobulin 3

Important Clinical Considerations

• Multifactorial etiology: Weakness may result from direct HIV effects, medication toxicity, opportunistic infections, or comorbid conditions 1

• Comorbidities to evaluate:

  • Vitamin deficiencies (B6, B12, folate)
  • Alcohol use disorders
  • Thyroid dysfunction
  • Diabetes mellitus
  • Syphilis 1

• Diagnostic pitfall: Lower extremity symptoms in HIV can be caused by pathology at any level of the nervous system (cortex to muscle), making bedside diagnosis challenging 4

• Treatment challenge: Neuropathic pain from HIV-associated DSP is difficult to manage and often responds poorly to conventional treatments 2

HIV-related extremity weakness significantly impacts quality of life and requires careful evaluation to determine the specific mechanism and appropriate management approach.