Recent developments in the HIV neuropathies.
OBJECTIVE
With the introduction of highly active antiretroviral therapy peripheral neuropathies have become the most common neurological complications in HIV infection. The frequency and spectrum of these neuropathies are changing, as the various toxic and immune factors are modified by new treatment strategies. Recent studies have provided a better understanding of the risk factors, markers and relevant pathogenic mechanisms, and a thorough review of these is critical for an improved understanding of this important and increasingly common complication.


RESULTS
The combined use of dideoxynucleosides, in association with immune-mediated mechanisms triggered by HIV infection, are critical in the development of distal sensory polyneuropathy. Valuable markers of neuropathy such as intraepidermal nerve fiber density from skin biopsies have been validated and promise to be a valuable tool in the detection and monitoring of distal sensory polyneuropathy. Markers of virological activity have also been associated with the severity of neuropathic pain in distal sensory polyneuropathy. In some instances, the enhanced viral suppression from antiretroviral agents may actually improve or decrease the frequency of certain types of neuropathy. New evidence supports mitochondrial toxicity as a principal mechanism for dideoxynucleoside-associated sensory neuropathy, and questions arise about enhanced risk with pre-existing mitochondrial defects. Confirmed treatments are limited to the reduction of symptoms, with a need for the further investigation of corrective therapies.


CONCLUSIONS
Increased and improved surveillance for HIV-associated neuropathy will allow earlier interventions to improve quality of life and prevent severe toxicities. A better understanding of the prevailing mechanisms will allow for more effective interventions.
Luciano
Carlos A
CA
Specialized Neuroscience Research Program in NeuroAIDS, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico 00936, USA.
Pardo
Carlos A
CA
McArthur
Justin C
JC
D015415:Biomarkers; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D010523:Peripheral Nervous System Diseases / Q000145:classification / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy / Q000821:virology*; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers