Peripheral neuropathy with nucleoside antiretrovirals - Risk factors, incidence and management

Distal symmetrical peripheral neuropathy is a common adverse experience in persons with HIV infection. This condition, which presents as a pain, numbn ess, burning and/or dysaethesia initially in the feet, is often multi-facto rial in its origin. Nucleoside analogue reverse transcriptase inhibitors re present an important contributor to peripheral neuropathy. Specifically, ar ound 10% of patients receiving stavudine or zalcitabine and 1 to 2% of dida nosine recipients may have to discontinue therapy with these agents due to neuropathy. Prompt withdrawal of these therapies enables gradual resolution of signs and symptoms in most patients, although a period of symptom inten sification may occur shortly after withdrawal. Risk factors for developing peripheral neuropathy during nucleoside analogu e therapy include low CD4+ cell count (< 100 cells/mm(3)), a prior history of an AIDS defining illness or neoplasm, a history of peripheral neuropathy , use of other neurotoxic agents including high alcohol (ethanol) consumpti on and nutritional deficiencies such as low serum hydroxocobalamin levels. Thus, patients at increased risk of peripheral neuropathy should potentiall y avoid the use of the neurotoxic nucleoside analogues or be more carefully monitored during therapy. Management of this problem includes patient educ ation, prompt withdrawal of the likely causative agent (giving consideratio n not to leave the patient on a sub-optimal therapy regimen) and simple ana lgesia, with augmentation with tricyclic antidepressants or anticonvulsant agents when pain is severe. New agents that may assist in managing this con dition include levacecarnine (acetyl-L-carnitine) and nerve growth factors such as recombinant human nerve growth factor.