Peripheral Neuropathy with Nucleoside Antiretrovirals

Abstract

Distal symmetrical peripheral neuropathy is a common adverse experience in persons with HIV infection. This condition, which presents as a pain, numbness. burning and/or dysaethesia initially in the feet, is often multi-factorial in its origin. Nucleoside analogue reverse transcriptase inhibitors represent an important contributor to peripheral neuropathy. Specifically, around 10% of patients receiving stavudine or zalcitabine and 1 to 2% of didanosine 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 intensification may occur shortly after withdrawal. Risk factors for developing peripheral neuropathy during nucleoside analogue therapy include low CD4+ cell count (<100 cells/mm3), a prior history of an AIDS defining illness or neoplasm, a history of peripheral neuropathy, use of other neurotoxic agents including high alcohol (ethanol) consumption and nutritional deficiencies such as low serum hydroxocobalamin levels. Thus, patients at increased risk of peripheral neuropathy should potentially avoid the use of the neurotoxic nucleoside analogues or be more carefully monitored during therapy. Management of this problem includes patient education. prompt withdrawal of the likely causative agent (giving consideration not to leave the patient on a sub-optimal therapy regimen) and simple analgesia. with augmentation with tricyclic antidepressants or anticonvulsant agents when pain is severe. New agents that may assist in managing this condition include levacecarnine (acetyl-L-carnitine) and nerve growth factors such as recombinant human nerve growth factor.

L-Acetylcarnitine: A Proposed Therapeutic Agent for Painful Peripheral Neuropathies

“…After treatment with antiretroviral drugs, 10-30% of patients report signs of drug-associated peripheral neuropathies, such as a bilateral pain and burning dysesthesia in the lower extremities [49,37,35,36]. In a non-randomized clinical trial, Famularo and colleagues reported that HIV patients with lower levels of L-acetylcarnitine in their sera developed painful peripheral neuropathies during treatment with synthetic nucleoside analogues such as Zidovudine (ZDV) or Didanosine (ddI), whereas patients that did not experience peripheral neuropathies during ZDV or ddI treatment had normal levels of L-acetylcarnitine [13].…”

Mitochondrial Alterations with Mitochondrial DNA Depletion in the Nerves of AIDS Patients with Peripheral Neuropathy Induced by 2′3′-Dideoxycytidine (ddC)

“…Since the time it was first introduced for the treatment of AIDS, ddC was causally connected with a dose-dependent, painful, sensorimotor axonal peripheral neuropathy (Berger et al, 1993;Blum et al, 1996;Dubinsky et al, 1989;Lewis and Dalakas, 1995;Moyle and Sadler, 1998). The neuropathy occurs in 34% of patients receiving ddC, and it is a limiting factor in the use of this drug in the treatment of AIDS (Dalakas, 2001;Dubinsky et al, 1989;Berger et al, 1993;Lewis and Dalakas, 1995;Blum et al, 1996;Moyle and Sadler, 1998).…”

Effect of Acupuncture Administered in a Group Setting on Pain and Subjective Peripheral Neuropathy in Persons with Human Immunodeficiency Virus Disease

“…However, as the life expectancy of HIV-infected individuals increases, the prevalence of peripheral neuropathies in individuals with HIV likely is increasing (Sacktor, 2002). This problem is exacerbated by the neuropathy that results from HAART in addition to HIV infection-related neuropathy and neuropathy resulting from opportunistic infections (Hurst, 1999;Moyle and Sadler, 1998;Patel et al, 1989). The HAART-related neuropathies generally result from administration of antiretrovirals such as zalcitabine, didanosine, or stavudine (Simpson and Tagliati, 1995).…”

“…eripheral neuropathy can result from the direct infection of neurons with human immunodeficiency virus (HIV), opportunistic infection of neurons because of generalized immunosuppression, and from highly active antiretroviral therapy (HAART) (Hurst, 1999;Moyle and Sadler, 1998). Furthermore, the increased life expectancy of HIV-infected individuals through HAART increases the prevalence of peripheral neuropathies (Sacktor, 2002).…”