HIV-Related Peripheral Neuropathy and Their Treatment

SKIN BIOPSIES TO MONITOR FOR NEUROPATHY: Justin McArthur, neurologist from Hopkins, said today in a State of the Art Lecture you can do these skin biopsies to monitor for neuropathy. I'll have more details in another email but he said doctors need to learn how to do this. You can monitor neuropathy by biopsy and address problem if it appears by treatment or therapy change.

McArthur said punch skin biopsy has been developed as a useful technique to demonstrate the loss of distal nerve fiber terminals. Nerve fiber regeneration is strikingly absent. He also talked about a few treatment possibilities in development and a new model for studying new treatments. NATAP is preparing a more in-depth discussion of his talk. McArthur is coming on my weekly radio show "Living Well With HIV & Hepatitis" this month to talk about all this. I will notify you of the date.

There is also a poster here saying that you can check lactate and if elevated this is associated with HIV meds neuropathy and you can alter therapy. These approaches need further study.
--JL

Lactate Concentrations Distinguish Between Nucleoside Neuropathy and HIV Distal Symmetrical Sensory Polyneuropathy

Background:
The clinical distinction between nucleoside neuropathy (NN), which may be related to mitochondrial dysfunction, and distal symmetrical polyneuropathy (DSPN), which may be related to active viral replication, is difficult. We sought to determine whether an elevated serum lactate concentration (a marker of mitochondrial dysfunction) and viral load could distinguish between NN and DSPN.

Methods:
A prospective study of HIV patients with and without peripheral neuropathy was performed. Of those patients who had a neuropathy, only those with recent onset over the preceding few weeks were included.

Results:
63 patients have been assessed: (none were taking ddI or ddC). 21 had a peripheral neuropathy, and in 15 of these d4T was the cause as demonstrated by improvement in all on cessation. 20 patients were taking d4T and did not have a neuropathy, while there were 22 patients who did not have a neuropathy and were not taking d4T. Of the 15 patients with d4T neuropathy, 13 had an elevated serum lactate concentration that returned to normal on drug cessation, and viral load was detectable in only one patient. Of the 6 patients thus far studied with DSPN, only one had an elevated serum lactate and 3 had an elevated plasma viral load. In the patients without a neuropathy, 3 had an elevated lactate (all on d4T) and 7 had an elevated viral load. By multivariate analysis, lactate concentrations were significantly associated with NN and not DSPN (p = 0.024) sensitivity, specificity and positive predictive value 86.7%, 83.3% and 92.9% respectively) while viral load was not associated with either NN or DPSN.

Conclusions:
These results suggest that an elevated serum lactate is useful in a patient with a neuropathy in whom NN is a possibility. More generally, the findings support the hypothesis that NN is related to mitochondrial dysfunction and DSPN is related to indirect mechanisms.