The Body Covers: The 7th European Conference on Clinical Aspects and Treatment of HIV-Infection
Satellite Symposium: Clinical Advances in the Treatment of HIV Disease
Identifying and Managing Toxicities: Disease or Therapy Related?
Sunday, October 24, 1999
Diagnosing and Treating Peripheral NeuropathyAuthored by Dr. David Simpson
Associate Professor of Neurology
Mt. Sinai Medical Center
New York, NY, USA
There are several complications of HIV infection, or its treatment, which involve the nervous system. One of the more common is called distal symmetrical polyneuropathy, and it is the most common peripheral neuropathy. The symptoms are most commonly either numbness or burning pain of the feet or hands, and it is usually on both sides of the body (symmetrical). There rarely is weakness observed unless significant damage has occurred. On a physical exam, the findings include decreased reflexes at the ankles compared to the knees, and an elevated threshold of vibration, pinprick and temperature sensation in the feet; however, joint position sense is usually normal. The symptoms can be mistaken for other types of neuropathy, such as carpal tunnel syndrome. It is most often described in those with advanced untreated HIV infection, although can also be seen as a consequence of treating HIV itself. Other conditions that can cause this type of neuropathy include diabetes, alcoholism, and vitamin B12 deficiency, and these should also be checked in someone with HIV. Older age and general health can also put someone at higher risk for this neuropathy. The actual cause of this neuropathy is unknown, although there is evidence of nerve damage with a loss of the nerve fiber (axon) seen universally.
Of the antivirals, the most common association with neuropathy is with the "d" drugs: ddC, ddI, and d4T. The current dose of d4T was selected in part because higher doses resulted in more neuropathy. Similarly, there may be some advantage for those having neuropathy on the "standard" dose of d4T to use it at a somewhat reduced dose, since there is some evidence that the antiviral effect may be preserved, while the impact on neuropathy is reduced. However, in a study (ACTG 175) done in the US comparing one versus two nucleosides, the highest incidence of neuropathy was seen in those taking AZT and ddC, and there was less neuropathy in those who were taking ddI instead of ddC.
The management of HIV associated neuropathy first depends on making an accurate diagnosis of the cause. First is to ensure that there are no other metabolic causes for the neuropathy as mentioned above. Next is to evaluate the regimen itself, and consider dose reductions if appropriate, or alternative medications with less neurotoxicity. However, it is noted that some neuropathy can be stable over prolonged periods of time, and drug substitutions may not be necessary in this circumstance especially if the symptoms are tolerable and if there are no desirable alternative medication choices.
Pain management can be done with a variety of approaches. The first is to consider medications that relieve pain. There are common medications that are used for this, including the nonsteroidal anti-inflammatory medications (ibuprofen and others), weak narcotics (codeine, oxycodone) and stronger narcotics (methadone, morphine). There have been studies of the use of tricyclic antidepressants for this type of neuropathy, as this class has shown benefit in those with diabetic neuropathy. However, in two studies of amitriptyline (one of the tricyclics) in HIV, the results were not better than placebo and thus use of this class is controversial for managing neuropathic pain. A study of mexiletine was also done, and results were also no better than placebo. There has been a successful study using a preparation of topical lidocaine, called Lidoderm. The results suggested significant pain relief, with 74% reporting moderate or excellent pain relief. The only side effect was dry skin, and further studies are underway to confirm these observations. (This medication should soon become available, at least in the US, initially as a patch; the gel form used in these studies may become available in the future.)
Another medication that has shown benefit is lamotrigine (brand name Lamictal). It is primarily used as an anti-seizure medication, but there is evidence of benefit in treating painful neuropathies. A placebo controlled trial demonstrated significant pain reduction over 14 weeks of use. Its primary side effect is a rash which occurred in 25% of patients using this medication -- decreasing the occurrence of the rash is being studied by starting with very low doses and building up the dose gradually. While another antiseizure medication, gabapentin (neurontin) is commonly mentioned, there is no data yet to guide us on the benefits of this medication. Finally, nerve growth factor was in active development for treating peripheral neuropathy, and there were early results suggesting benefit. However, the manufacturer announced that it was stopping further development of this drug, and the future of this class of compounds is uncertain. Ongoing research continues to better understand the fundamental causes of neuropathy, so that new treatments can be developed based on better understanding what is causing the injury to the nerve.
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