February 6, 2001
Justin McArthur from Johns Hopkins provided an overview of HIV-related neuropathy in his State-of-the-Art Lecture (L8). The important impact that peripheral neuropathy makes on quality of life was emphasized. Peripheral neuropathy (PN) is often under-diagnosed and under treated. A patient suffering from peripheral neuropathy often has limited choices in subsequent therapy and has a disincentive to be highly compliant if the problem is related to treatment.
Sensory PN in the setting of HIV infection usually involves the longest nerves in the body. Thus, the most common manifestations relate to pain in the soles of the feet or paresthesia involving the feet. HIV can cause a sensory peripheral neuropathy but there are often other factors present that confound the problem. In one cited study (by David Simpson), 139/300 patients had another factor known to contribute (most commonly diabetes, alcohol use, use of dapsone, or use of one of the dideoxynucleoside agents).
The risk for sensory PN is related to the viral load. Other factors that increase the risk for sensory PN include age, wasting syndrome, the CD4 count, and the presence of other causes for PN. The pathology of HIV-sensory PN involves the degeneration of unmyelinated nerve fibers, which can be detected by skin biopsy. Often there is an associated increase in surrounding macrophage activation with some swelling. One possible pathogenic mechanism is mitochondrial toxicity. There is an association between increased lactic acid levels and an increased rate of PN.
In one study conducted at Johns Hopkins, the rate for sensory PN was 5-6% among patients taking ZDV/3TC, 7-8% for patients on ddI, 20% for patients on ddI/d4T, and 25% for patient on ddI/d4T and hydroxyurea.
Efforts to better understand HIV-related PN have been frustrated by lack of an animal model or a good surrogate marker in humans. Dr. McArthur described a new test involving the use of a capsaicin skin patch. Exposure to capsaicin results in the loss of the density of fine neurons, as measured upon skin biopsy. Normal subject regenerate sensory neurons within about 60 days while persons with diabetes show delayed regenerative capacity. This test has promise in helping to more rapidly evaluate interventions to treat HIV related PN.
Controlled clinical trials evaluating potential treatments for PN have yielded mixed results. In one study comparing amitryptiline versus acupuncture no benefit was seen. Other studies compared amitryptiline versus mexilitine (trend favoring amitryptiline), lamotrigine (some benefit), topical lidocaine (no benefit), and recombinant human nerve growth factor (benefit seen but company interest withdrawn). These studies have taught investigators many lessons particularly related to the need for a good surrogate marker (perhaps the capsaicin skin test). There are some data that uridine might work to rescue neurons damaged by PN. There is also interest in a class of compounds known as neurophilins. Dr. McArthur did not discuss whether use of any vitamins, minerals, or antioxidants could have any role in the prevention or treatment of HIV-related sensory PN. The take-home lesson from this captivating lecture (great graphics attributed to the speaker's 15-year-old daughter) related to the significant impact that sensory PN has on the life of HIV-infected persons and the current frustration about our understanding and treatment options.
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