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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Peripheral Nervous System Toxicity

(Last updated: February 12, 2014; last reviewed: February 12, 2014)

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Table 11k. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Peripheral Nervous System Toxicity
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequencya Risk Factors Prevention/ Monitoring Management
ARV Toxic Neuropathyb d4T, ddI Onset
  • Variable, weeks to months following NRTI initiation
  • Decreased sensation
  • Aching, burning, painful numbness
  • Hyperalgesia (lowered pain threshold)
  • Allodynia (non noxious stimuli cause pain)
  • Decreased or absent ankle reflexes
  • Bilateral soles of feet, ascending to legs and fingertips
HIV-Infected Children:
  • 1.13% prevalence (baseline 2001); incidence 0.23 per 100 person-years (2001–2006) in a U.S. cohort.
  • <1% discontinued d4T because of neuropathy in 3 large African cohorts (aged 1 month–18 years; median follow-up 1.8–3.2 years).
HIV-Infected Adults on d4T:
  • Prevalence up to 57% 
  • Incidence rates 6.4–12.1 per 100 person-years
HIV-Infected Adults:
  • Pre-existing neuropathy (e.g., diabetes, alcohol abuse, vitamin B12 deficiency)
  • Elevated triglyceride levels
  • Older age
  • Poor nutrition
  • More advanced HIV disease
  • Concomitant use of other neurotoxic agents (e.g., INH)
  • Some mitochondrial DNA haplogroups may have increased risk
Limit use of d4T and ddI, if possible.

As part of routine care, monitor for symptoms and signs of peripheral neuropathy.
Discontinue offending agent.

Persistent pain can be difficult to treat; topical capsaicin 8% may be helpful. 

Data are Insufficient to Allow the Panel to Recommend Use of any of the Following Modalities in Children
  • tricyclic antidepressants
  • gabapentin
  • pregabalin
  • mexilitine
  • lamotrigine
Consider referral to neurologist.
a Peripheral neuropathy may be under-reported in children because symptoms are difficult to evaluate in young children.
b HIV infection itself may cause a distal sensory neuropathy that is phenotypically identical to ARV toxic neuropathy.

Key to Acronyms: ARV = antiretroviral; d4T = stavudine; ddI = didanosine; INH = isoniazid; NRTI = nucleoside reverse transcriptase inhibitor


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