Background:  The sensory neuropathies associated with HIV infection (HIV-SN) are a major cause of morbidity in individuals with HIV infection. Ther 2 main types are:  distal sensory polyneuropathy, associated with HIV/AIDS, and antiretroviral toxic neuropathy, associated with exposure to didanosine (ddI), lamivudine (d4T), and dideoxycytidine (ddC). Use of d4T or ddI increases the risk of symptomatic sensory neuropathy by several fold, and globally the incidence of neuropathy may increase with the use of fixed drug combinations containing d4T. Other risk factors include age, mitochondrial and cytokine genotypes, and vitamin deficiencies. Neither hepatitis C co-infection nor the metabolic syndrome appears to be an amplifier. HIV-infected subjects have impaired nerve regeneration rates compared to healthy control subjects, and this “repair” gap may explain the susceptibility to neuropathy. The pathology of HIV-SN is characterized by “dying back” or sensory axonal degeneration and a more modest loss of dorsal root ganglion (DRG) sensory neurons with prominent macrophage infiltration. Animal models and in vitro models have been developed, and have elucidated some of the mechanisms of nerve injury. For example, ddC-induced neuropathy is mediated primarily through effects on mitochondria, while gp120 induces neuritic degeneration and neuronal apoptosis. The Schwann cells, the cells that ensheath peripheral nerve axons, mediate this neurotoxicity.

Conclusions:  Currently, there are no effective therapies for HIV-SN except for symptomatic control with anticonvulsants, selective antidepressants, or topical capsaicin (in high concentration). The hormone erythropoietin (EPO) prevents sensory axonal degeneration and in vitro neuronal death by both gp120 and ddC. EPO may be useful in the treatment of HIV-SN, and a controlled trial is underway.