Causes

People with HIV can experience neuropathy due to the direct effects of HIV on the nervous system, at any stage of infection, or because of opportunistic infections and tumours which affect the nervous system. Autonomic neuropathy in particular may be a direct effect of HIV.1  Neuropathy can also be caused by prescription drugs including some anti-HIV drugs, recreational drugs and alcoholism. (A more detailed review of the causes of neuropathies in people with HIV was published in HIV & AIDS Treatment in Practice, NAM's electronic newsletter on HIV treatment in resource-limited settings, in 2009).

Neuropathy is a common side-effect of the anti-HIV drugs ddI (didanosine, Videx / VidexEC), d4T (stavudine, Zerit) and ddC (zalcitabine, Hivid). It is not associated with the other NRTIs, nor with protease inhibitors or non-nucleoside reverse transcriptase inhibitors. The addition of hydroxycarbamide (Hydrea) to ddI and d4T may enhance the antiviral effectiveness of these drugs and increase the risk of peripheral neuropathy. Recently, NRTI-related neuropathy has been linked to other class-specific side-effects thought to be caused by damaged to the mitochondria in human cells.2 3 4 See Lactic acidosis for further details.

Peripheral neuropathy is the side-effect most frequently seen in people taking d4T-based regimens in resource-limited settings.5 6 In 2007 the World Health Organization revised its adult treatment guidelines to recommend that a dose of 30mg twice daily should be used in patients weighing more than 60kg, since a meta-analysis had shown that this dose was associated with a lower risk of side-effects.7

Drugs used to treat many HIV-related conditions and opportunistic illnesses may also cause neuropathy including isoniazid, vincristine (Oncovin), lithium carbonate (Camolit / Liskonum / Priadel), dapsone, metronidazole (Flagyl / Flagyl S / Metrolyl), pyridoxine (vitamin B6), thalidomide, cytomegalovirus infection and syphilis. Other possible causes of these symptoms include alcohol and some recreational drugs such as heroin, cocaine, or amphetamines.

It seems that these different causes of neuropathy can interact. People with mild neuropathy symptoms often find that they intensify after they start taking treatments such as ddI.

Neuropathy has been associated with a deficiency of the B vitamins, especially vitamin B12.

Factors associated with the development of peripheral neuropathy in a large cohort of HIV-infected patients include older age, diabetes and white race. The risk of peripheral neuropathy is elevated associated with the first year of treatment with drugs such as ddI, but long-term exposure to anti-HIV drugs reduces the risk.8

The risk of developing peripheral neuropathy during antiretroviral treatment is considerably increased for individuals with a particular genetic profile. Individuals with mitochondrial haplogroup T, who comprise 10 to 15% of the Caucasian population, have a fivefold greater risk of developing peripheral neuropathy compared with the rest of the population.9 The genetic markers predicting peripheral neuropathy have not yet been investigated in poulations of African origin due to much greater diversity of mitochondrial haplotypes, making such research much more complex.

References

  1. Neild P et al. Autonomic function (AF) in HIV infection: relationship to stage of disease, systemic opportunistic infections (OI) and prognosis. Fourth Annual Meeting of the British HIV Association, Oxford, abstract 4, 1998
  2. Brew B et al. Lactate concentrations distinguish between nucleoside neuropathy and HIV distal symmetrical sensory polyneuropathy. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 9, 2001
  3. Dalakas MC et al. Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC). Lab Investig 81: 1537-1544, 2001
  4. Rabing Christensen E et al. Mitochondrial DNA levels in fat and blood cells from patients with lipodystrophy or peripheral neuropathy and the effect of 90 days of high-dose coenzyme Q treatment: a randomized, double-blind, placebo-controlled pilot study. Clin Infect Dis 39: 1371-1379, 2004
  5. Amoroso A et al. ARV-associated drug toxicities leading to a switch in medication: experience in Uganda, Kenya and Zambia. Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, abstract 789, 2007
  6. Wright E et al. Neurocognitive impairment, symptomatic peripheral neuropathy and depression are highly prevalent in HIV-infected outpatients within Asia Pacific: findings of the Asia Pacific NeuroAIDS consortium (APNAC) study. Sixteenth International AIDS Conference, Toronto, abstract MoAb0302, 2006
  7. Hill A et al. Systematic review of clinical trials evaluating low doses of stavudine as part of antiretroviral treatment. Expert Opin Pharmacother 8 (5): 679-688, 2007
  8. Lichtenstein K et al. Factors associated with peripheral neuropathy in the HIV Outpatient Study Cohort (HOPS). Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris (Antiviral Therapy 8:1), abstract 729, 2003
  9. Hulgan T et al. Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study. AIDS 19: 1341-1349, 2005
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