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HIV Neuropathies—
Several disorders, no proven treatments

by Stephen Brown, M.D. and Sy Young, M.D.

The sensation can be described as the "pins and needles" feeling you get when your foot falls asleep, but it occurs all the time. It could be sharp, stabbing or burning pain in the feet or hands, making basic tasks and day to day life difficult.

About 20 — 35% of HIV-infected individuals eventually experience some symptoms of neuropathy, a general term for disease of the peripheral nerves. These are the nerves that radiate from the spine and the brain, and carry sensory information (i.e., pain, touch, pressure) as well as the commands for movement of the muscles. The most common HIV-associated neuropathies are polyneuropathies, meaning that more than one peripheral nerve is affected.

Neuropathies comprise a heterogeneous group of disorders, and in HIV infection several causes of neuropathy have been suggested. Some neuropathies seen in HIV/AIDS are due to toxic side-effects of drugs administered either to suppress HIV or to treat other complications (see the accompanying table). It is still a matter of debate as to whether some neuropathies are caused by direct infection of nerves by HIV. In some cases, neuropathy appears to result from infection of the peripheral nerves with cytomegalovirus (commonly known as CMV).

Since a number of drugs commonly prescribed for HIV+ individuals can cause a peripheral neuropathy, it can be crucial to correctly ascertain what is causing the symptoms. An accurate diagnosis of drug-induced neuropathy is possible, particularly if the onset of neuropathy coincides with the initiation of a suspect drug. Drug-induced neuropathy can often be treated by withdrawing the offending drug (or, possibly, by reducing the dosage), although symptoms may not abate immediately. Sometimes, the symptoms do not reverse at all. (Always check with a doctor before discontinuing any medication).

Partial list of drugs that can cause peripheral neuropathy.

Before the onset of the AIDS epidemic, one of the most frequent causes of neuropathy was diabetes. Many treatments have been tried for diabetic neuropathy, with varying degrees of success. Among the common treatments for such painful neuropathies include both narcotic and non-narcotic pain killers, antidepressant drugs such as amitriptyline, anticonvulsant drugs such as carbamazepine, dilantin and gabapentin, and the local anesthetic mexiletine.

Many of these same medications have been tried in HIV neuropathy, although until recently there has been little success in controlled clinical trials. Given the lack of an effective treatment, other therapeutic approaches have also been attempted. Several studies on HIV associated neuropathy are summarized below.

Published studies on treatments for HIV-associated neuropathy.

*Funded via a grant to Wilbert C. Jordan, MD, MPH, Director of the Oasis Clinic, by AIDS Research Alliance of America.

1. La Spina, I., et al., Gabapentin (GBP) in painful AIDS-related neuropathy. 51st American Academy of Neurology, 1999.
2. Jordan, W.C., The effectiveness of intermittent hyperbaric oxygen in relieving drug- induced HIV-associated neuropathy. J Natl Med Assoc, 1998. 90(6): p. 355-8.
3. Salim, Y.S., et al., [Plasmapheresis in the treatment of peripheral HIV neuropathy]. Ugeskr Laeger, 1989. 151(27): p. 1754-6.
4. Kemper, C.A., et al., Mexiletine for HIV-infected patients with painful peripheral neuropathy: a double-blind, placebo-controlled, crossover treatment trial. J Acquir Immune Defic Syndr Hum Retrovirol, 1998. 19(4): p. 367-72.
5. Kieburtz, K., et al., A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team. Neurology, 1998. 51(6): p. 1682-8.
6. Shlay, J.C., et al., Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: a randomized controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS. Jama, 1998. 280(18): p. 1590-5.
7. Simpson, D.M., et al., Peptide T in the treatment of painful distal neuropathy associated with AIDS: results of a placebo-controlled trial. The Peptide T Neuropathy Study Group. Neurology, 1996. 47(5): p. 1254-9.

As can be seen from the table, several researchers have reported limited improvements in small studies, using interventions such as gabapentin, nerve growth factor, hyperbaric oxygen (participants breathed 100% oxygen), and plasmapheresis (in which a patient's blood cells are separated from the blood plasma and returned to the individual). However, in none of these trials were the treatments compared to either an inactive placebo or to another treatment intervention. This is important because in pain research, the placebo effect can be substantial, and the improvements that were reported might merely reflect this effect and not be the result of a truly effective therapy.

Although no treatment has yet been proven in a controlled clinical trial to effectively cure or reverse HIV neuropathy, it is still worthwhile for those suffering from neuropathic symptoms to have a physician evaluate their condition. Some neuropathies, as discussed above, can be managed by addressing the cause (i.e., medications). In other cases, pain management techniques such as biofeedback, and some medications, can offer symptomatic relief. Furthermore, by preventing further deterioration, treatment can be designed to maintain one's quality of life.

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