Nucleoside analogues and neuropathy in the era of HAART.
BACKGROUND
Sensory neuropathies occur commonly in the setting of HIV infection. Sensory neuropathy (SN) is clearly associated with HIV itself, and in this context develops in association with increased macrophage activation in the peripheral nervous system. A clinically identical SN may also occur as a consequence of exposure to some HIV treatments. In this setting, impaired mitochondrial function is thought to play a role in the development of neurological dysfunction.


OBJECTIVE
This review explores the evidence for the neurotoxicity of HIV and HIV treatments, the effect of nucleoside reverse transcriptase inhibitors on mitochondria, and the likely associations between these.


CONCLUSIONS
Dideoxynucleotide drugs are commonly associated with SN. The nucleoside reverse transcriptase inhibitors inhibit mitochondrial DNA synthesis and may thus exacerbate existing viral-induced nerve damage.
Cherry
Catherine L
CL
Department of Infectious Diseases and Microbiology, The Alfred Hospital, Commercial Road, 3181 Prahran, Melbourne, Vic, Australia. kate.cherry@med.monash.edu.au
McArthur
Justin C
JC
Hoy
Jennifer F
JF
Wesselingh
Steven L
SL
D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D015224:Dideoxynucleosides / Q000009:adverse effects; D004195:Disease Models, Animal; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009422:Nervous System Diseases / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000473:pathology; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects
D004272:DNA, Mitochondrial; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors