Recent advances in HIV neuropathy

Abstract

To describe recent advances in HIV neuropathy. Epidemiologic studies since highly active antiretroviral therapy was introduced have shown that the incidence of HIV-associated distal sensory polyneuropathy is reduced. Studies have also shown the relationship between distal sensory polyneuropathy and the use of neurotoxic antiretroviral drugs. Skin punch biopsy for assessment of epidermal nerve fiber density is valuable both for diagnosis of distal sensory polyneuropathy and as a predictor of the condition occurring in the future. An in-vitro model of antiretroviral toxic neuropathy showed that dideoxynucleoside analogues that cause neuropathy exert direct mitochondrial toxicity that is not mediated indirectly through the inhibition of DNA polymerase-gamma. HIV envelope protein gp120 exerts axonal toxicity directly or indirectly via perineuronal Schwann cells. A feline model of HIV, infection of neonatal cats with the feline immunodeficiency virus, showed development of peripheral neuropathy characterized by loss of epidermal innervation. While epidemiological studies of HIV-associated peripheral neuropathy continue to provide useful information, pathogenic studies are moving forward. Animal models of the disease will allow researchers to 'manipulate' the system. It is hoped that these types of studies will translate to an improved understanding of the pathogenesis of HIV-associated neuropathies leading to better treatments.