What is the pathophysiology of HIV-associated distal painful sensorimotor polyneuropathy?

Updated: Aug 08, 2019
  • Author: Florian P Thomas, MD, PhD, MA, MS; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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Small fiber neuropathy typically involves distal degeneration of small or unmyelinated nerve fibers. The pattern of neuropathy is different for polyneuropathy caused by direct HIV infection, which affects all fibers, compared with that induced by antiretroviral treatment, which affects small fibers. [8]

Autonomic dysfunction is common in HIV infection and is associated with distal symmetric polyneuropathy. [9]

More than one pathophysiologic mechanism likely exists. HIV may act directly by infecting dorsal root ganglion neurons. However, there may also be an indirect mechanism where neurons are injured by infiltrating macrophages, which release proinflammatory chemokines and free radicals. [10]

Since the advent of HAART, several studies have shown a lack of association between distal painful sensorimotor polyneuropathy and the degree of immunosuppression, including CD4 counts and viral load. Several HAART medications may be toxic to mitochondria by inhibiting mitochondrial DNA polymerase. [11, 12, 13]  The latest 2013 WHO guidelines have sought to phase out d4T therapy in underdeveloped countries as first-line treatment. 

Distal epidermal denervation has been shown to be associated with distal painful sensorimotor polyneuropathy. [14] Other factors may be involved, including nutritional and vitamin deficiencies (eg, vitamin B-12). [15]

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