A proposed management algorithm for late-onset efavirenz neurotoxicity

Area of Science:

• Pharmacology
• Neuroscience
• Infectious Diseases

Background:

• High rates of co-prescription of efavirenz (EFV) and isoniazid (INH) in HIV-positive patients in South Africa.
• EFV metabolism via CYP2B6 is subject to genetic polymorphism, potentially slowing drug clearance.
• INH metabolism inhibits pathways crucial for slow EFV metabolizers, impacting EFV plasma levels.

Purpose of the Study:

• To investigate the probable role of concomitant INH use in the development of EFV neurotoxicity.
• To describe the clinical features, investigations, and outcomes of patients experiencing EFV toxicity.
• To suggest a potentially limited diagnostic work-up for suspected cases.

Main Methods:

• Retrospective case record audit of seven patients presenting with EFV toxicity.
• Tertiary-level neurological assessment.
• Review of clinical features, investigation results, and outcomes after EFV discontinuation.

Main Results:

• Observed increase in EFV toxicity cases presenting to a neurology referral unit.
• All reported cases were associated with recent initiation of concomitant INH therapy.
• Detailed clinical features, investigation findings, and outcomes are presented.

Conclusions:

• Concomitant INH use is strongly implicated in the development of EFV-associated neurotoxicity, particularly late-onset syndromes.
• Toxic EFV plasma levels are a key factor in this neurotoxicity.
• A focused diagnostic approach may be sufficient for suspected cases of INH-induced EFV toxicity.