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AIDS and AIDS-treatment neuropathies

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Abstract

AIDS and AIDS-treatment neuropathies are common in individuals infected with HIV. As patients live longer due to improved antiretroviral therapies, the impact of painful neuropathy on patients’ lives may increase. Several antiretroviral medications are known to cause toxic neuropathy in patients with AIDS, but this may be outweighed by the beneficial effects of viral suppression. Current theories on the pathogenesis of AIDS neuropathies include mitochondrial toxicity secondary to γ-DNA polymerase inhibition and subsequent abnormal mitochondrial DNA synthesis. Treatment of AIDS neuropathies is directed toward relief of symptoms; however, new evidence suggests that aggressive antiretroviral therapy may also be effective.

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References and Recommended Reading

  1. d’Arminio Monforte A, Duca PG, Vago L, et al.: Decreasing incidence of CNS AIDS-defining events associated with antiretroviral therapy. Neurology 2000, 54:1856–1859.

    Google Scholar 

  2. Clifford DB, Yiannoutsos C, Glicksman M, et al.: HAART improves prognosis in HIV-associated progressive multifocal leukoencephalopathy. Neurology 1999, 52:623–625.

    PubMed  CAS  Google Scholar 

  3. Martin C, Solders G, Sonnerborg A, et al.: Antiretroviral therapy may improve sensory function in HIV-infected patients: a pilot study. Neurology 2000, 54:2120–2127. This pilot study of 49 HIV-infected patients was the first to demonstrate that lowering plasma HIV RNA viral load with antiretroviral therapy improves objective parameters of sensory nerve function.

    PubMed  CAS  Google Scholar 

  4. Sacktor NC, Lyles RH, Skolasky RL, et al.: Combination antiretroviral therapy improves psychomotor speed performance in HIV-seropositive homosexual men. Multicenter AIDS Cohort Study (MACS). Neurology 1999, 52:1640–1647.

    PubMed  CAS  Google Scholar 

  5. Wulff EA, Simpson DM: Neuromuscular complications of the human immunodeficiency virus type 1 infection. Semin Neurol 1999,19:157–164.

    PubMed  CAS  Google Scholar 

  6. Bacellar H, Munoz A, Miller EN, et al.: Temporal trends in the incidence of HIV-1-related neurologic diseases: Multicenter AIDS Cohort Study, 1985–1992. Neurology 1994, 44:1892–1900.

    PubMed  CAS  Google Scholar 

  7. Tagliati M, Grinnell J, Godbold J, Simpson DM: Peripheral nerve function in HIV infection: clinical, electrophysiological, and laboratory findings. Arch Neurol 1999, 56:84–89. This study comprehensively assessed 251 consecutive HIV-infected individuals and evaluated the multifactorial etiologies of painful polyneuropathy.

    Article  PubMed  CAS  Google Scholar 

  8. Marra CM, Boutin P, Collier A, et al.: Screening for distal sensory peripheral neuropathy in HIV-infected persons in research and clinical settings. Neurology 1998, 51:1678–1681.

    PubMed  CAS  Google Scholar 

  9. Simpson DM, Tagliati M: Nucleoside analogue-associated peripheral neuropathy in human immunodeficiency virus infection. J Acquir Immune Defic Syndr Hum Retrovirol 1995, 9:153–161.

    PubMed  CAS  Google Scholar 

  10. Wulff EA, Wang AK, Simpson DM: HIV-associated peripheral neuropathy: epidemiology, pathophysiology and treatment. Drugs 2000, 59:1251–1260.

    Article  PubMed  CAS  Google Scholar 

  11. Williams D, Shah NR, Simpson DM: HIV-associated neuromuscular syndromes. In Approach Towards Management of Human Immunodeficiency Virus Infection and Its Related Complications. Edited by Singh N, Swindells. 2001, in press.

  12. dela Monte SM, Gabuzda DH, Ho DD, et al.: Peripheral neuropathy in the acquired immunodeficiency syndrome. Ann Neurol 1988, 23:485–492.

    Article  PubMed  Google Scholar 

  13. Mah V, Vartavarian LM, Akers MA, et al.: Abnormalities of peripheral nerve in patients with human immunodeficiency virus infection. Ann Neurol 1988, 24:713–717.

    Article  PubMed  CAS  Google Scholar 

  14. Cornblath DR, McArthur JC: Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 1988, 38:794–796.

    PubMed  CAS  Google Scholar 

  15. McCarthy BG, Hsieh ST, Stocks A, et al.: Cutaneous innervation in sensory neuropathies: evaluation by skin biopsy. Neurology 1995, 45:1848–1855.

    PubMed  CAS  Google Scholar 

  16. McArthur JC, Stocks EA, Hauer P, et al.: Epidermal nerve fiber density: normative reference range and diagnostic efficiency. Arch Neurol 1998, 55:1513–1520.

    Article  PubMed  CAS  Google Scholar 

  17. Berger AR, Arezzo JC, Schaumburg HH, et al.: 2’,3’-dideoxycytidine (ddC) toxic neuropathy: a study of 52 patients. Neurology 1993, 43:358–362.

    PubMed  CAS  Google Scholar 

  18. Bouhassira D, Attal N, Willer J, et al.: Painful and painless peripheral sensory neuropathies due to HIV infection: a comparison using quantitative sensory evaluation. Pain 1999, 80:265–272.

    Article  PubMed  CAS  Google Scholar 

  19. Childs EA, Lyles RH, Selnes OA, et al.: Plasma viral load and CD4 lymphocytes predict HIV-associated dementia and sensory neuropathy. Neurology 1999, 52:607–613. This large analysis of over 1600 HIV-seropositive men without AIDS from the Multicenter AIDS Cohort demonstrated a relationship between elevated plasma HIV-RNA viremia and a greater than twofold increase in the hazard for decreased sensory perception.

    PubMed  CAS  Google Scholar 

  20. Moore RD, Wong WM, Keruly JC, et al.: Incidence of neuropathy in HIV-infected patients on monotherapy versus those on combination therapy with didanosine, stavudine and hydroxyurea. AIDS 2000, 14:273–278. This study demonstrated the synergistic effect of combination antiretroviral therapy versus monotherapy on the incidence of decreased sensory perception.

    Article  PubMed  CAS  Google Scholar 

  21. Figg WD: Peripheral neuropathy in HIV patients after isoniazid therapy initiated. DICP 1991, 25:100–101.

    PubMed  CAS  Google Scholar 

  22. Gill P, Rarick M, Bernstein-Singer M, et al.: Treatment of advanced Kaposi’s sarcoma using a combination of bleomycin and vincristine. Am J Clin Oncol 1990, 13:315–319.

    Article  PubMed  CAS  Google Scholar 

  23. Ochonisky S, Verroust J, Bastuji-Garin S, et al.: Thalidomide neuropathy incidence and clinico-electrophysiologic findings in 42 patients. Arch Dermatol 1994, 130:66–69.

    Article  PubMed  CAS  Google Scholar 

  24. Famularo G, Moretti S, Marcellini S, et al.: Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. AIDS 1997, 11:185–190.

    Article  PubMed  CAS  Google Scholar 

  25. Yoshioka M, Shapshak P, Srivastava AK, et al.: Expression of HIV-1 and interleukin-6 in lumbosacral dorsal root ganglia of patients with AIDS. Neurology 1994, 44:1120–1130.

    PubMed  CAS  Google Scholar 

  26. Moyle GJ, Sadler M: Peripheral neuropathy with nucleoside antiretrovirals: risk factors, incidence and management. Drug Safety 1998, 19:481–494.

    Article  PubMed  CAS  Google Scholar 

  27. Dubinsky RM, Yarchoan R, Dalakas M, et al.: Reversible axonal neuropathy from the treatment of AIDS and related disorders with 2’,3’-dideoxycytidine (ddC). Muscle Nerve 1989, 12:856–860.

    Article  PubMed  CAS  Google Scholar 

  28. Browne MJ, Mayer KH, Chafee SB, et al.: 2′,3′-didehydro-3′-deoxythymidine (d4T) in patients with AIDS or AIDS-related complex: a phase I trial. J infect Dis 1993, 167:21–29.

    PubMed  CAS  Google Scholar 

  29. Simpson DM, Katzenstein DA, Hughes MD, et al.: Neuromuscular function in HIV infection: analysis of a placebocontrolled combination antiretroviral trial. AIDS Clinical Group 175/801 Study Team. AIDS 1998, 12:2425–2432.

    Article  PubMed  CAS  Google Scholar 

  30. Pike IM, Nicaise C: The didanosine expanded access program: safety analysis. Clin Infect Dis 1993, 16(suppl 1):S63-S68.

    PubMed  Google Scholar 

  31. Kakuda TN: Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Clin Ther 2000, 22:685–708.

    Article  PubMed  CAS  Google Scholar 

  32. Pan-Zhou XR, Cuil JR, Zhou XJ, et al.: Differential effects of antiretroviral nucleoside analogues on mitochondrial function in HepG2 cells. Antimicrob Agents Chemother 2000, 44:496–503.

    Article  PubMed  CAS  Google Scholar 

  33. Brinkman K, Hofstede HJ, Burger DM, et al.: Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 1998, 12:1735–1744.

    Article  PubMed  CAS  Google Scholar 

  34. Brinkman K, Smeitink JA, Romijn JA, et al.: Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. Lancet 1999, 354:1112–1115. This article proposes mitochondrial toxicity as the etiology of antiretroviral (ARV)-related lipodystrophy and presents evidence that may support the developing hypothesis that neuropathy is included in the spectrum of disorders that may result from ARV-induced mitochondrial toxicity.

    Article  PubMed  CAS  Google Scholar 

  35. Larsson NG, Tulinius MH, Holme E, et al.: Segregation and manifestations of the mtDNA tRNA(Lys) A--->G(8344) mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome. Am J Hum Genet 1992, 51:1201–1212.

    PubMed  CAS  Google Scholar 

  36. Mhiri C, Baudrimont M, Bonne G, et al.: Zidovudine myopathy: a distinctive disorder associated with mitochondrial dysfunction. Ann Neurol 1991, 29:606–614.

    Article  PubMed  CAS  Google Scholar 

  37. Hashimoto KI, Tsunoda R, Okamoto M, et al.: Stavudine selectively induces apoptosis in HIV type 1-infected cells. AIDS Res Hum Retroviruses 1997, 13:193–199.

    Article  PubMed  CAS  Google Scholar 

  38. Cepeda JA, Wilks D: Excess peripheral neuropathy in patients treated with hydroxyurea plus didanosine and stavudine for HIV infection. AIDS 2000, 14:332–333.

    Article  PubMed  CAS  Google Scholar 

  39. Moyle G: Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity. Clin Ther 2000, 22:911–936.

    Article  PubMed  CAS  Google Scholar 

  40. Wulff EA, Simpson DM: HIV-associated neuropathy: recent advances in management. HIV Adv Res Ther 1998, 8:23–29.

    Google Scholar 

  41. Katzenstein D, Haidich AB, Simpson D, et al., for the ACTG 291 Study Team: HIV-1 RNA levels, antiretroviral therapy, and distal sensory polyneuropathy in participants of ACTG 291 [abstract]. J Neurovirol 2000, 6:428.

    Google Scholar 

  42. Blum AS, Dal Pan GJ, Feinberg J, et al.: Low-dose zalcitabinerelated toxic neuropathy. Neurology 1996, 46:999–1003.

    PubMed  CAS  Google Scholar 

  43. Grond S, Zech D, Schug SA, et al.: Validation of World Health Organization guidelines for cancer pain relief during the last days and hours of life. J Pain Symptom Management 1991, 6:411–422.

    Article  CAS  Google Scholar 

  44. Dorfman D, Dalton A, Khan A, et al.: Treatment of painful distal sensory polyneuropathy in HIV-infected patients with a topical agent: results of an open-label trial of 5% lidocaine gel. AIDS 1999, 13:1589–1590.

    Article  PubMed  CAS  Google Scholar 

  45. Kieburtz K, Simpson D, Yiannoutsos C, et al.: A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team. Neurology 1998, 51:1682–1688.

    PubMed  CAS  Google Scholar 

  46. Newshan G: HIV neuropathy treated with gabapentin. AIDS 1998, 12:219–221.

    PubMed  CAS  Google Scholar 

  47. Rosner H, Rubin L, Kestenbaum A: Gabapentin adjunctive therapy in neuropathic pain states. Clin J Pain 1996, 12:56–58.

    Article  PubMed  CAS  Google Scholar 

  48. Simpson DM, Olney R, McArthur JC, et al.: A placebocontrolled trial of lamotrigine for painful HIV-associated neuropathy. Neurology 2000, 54:2115–2119.

    PubMed  CAS  Google Scholar 

  49. Rask CA: Biological actions of nerve growth factor in the peripheral nervous system. Eur Neurol 1999, 41:14–19.

    Article  PubMed  CAS  Google Scholar 

  50. McArthur JC, Yannoutsos C, Simpson DM, et al.: A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. AIDS Clinical Trials Group Team 291. Neurology 2000, 54:1080–1088.

    PubMed  CAS  Google Scholar 

  51. Simpson DM, Olney RK: Peripheral neuropathies associated with human immunodeficiency virus infection. In Peripheral Neuropathies: New Concepts and Treatments. Edited by Dyck PJ. Philadelphia: WB Saunders;1992:685–711.

    Google Scholar 

  52. Paice JA, Estwing-Ferrans C, Lashley FR, et al.: Topical capsaicin in the management of HIV-associated peripheral neuropathy. J Pain Symptom Management 2000, 19:45–51.

    Article  CAS  Google Scholar 

  53. Shlay JC, Chaloner K, Max MB, 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, 280:1590–1595.

    Article  PubMed  CAS  Google Scholar 

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  1. Mount Kisco Medical Group, 90 South Bedford Road, 10549, Mount Kisco, NY, USA

    Derek Williams R-PA, Anthony Geraci MD & David M. Simpson MD

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  1. Derek Williams R-PA
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Williams, D., Geraci, A. & Simpson, D.M. AIDS and AIDS-treatment neuropathies. Current Science Inc 6, 125–130 (2002). https://doi.org/10.1007/s11916-002-0008-7

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