Advertisement

Journal of NeuroVirology

, Volume 19, Issue 6, pp 557–564 | Cite as

Peripheral neuropathy in ART-experienced patients: prevalence and risk factors

  • Huichao Chen
  • David B. Clifford
  • Lijuan Deng
  • Kunling Wu
  • Anthony J. Lee
  • Ronald J. Bosch
  • Sharon A. Riddler
  • Ronald J. Ellis
  • Scott R. Evans
Article

Abstract

Peripheral neuropathy (PN) is a common neurological complication of HIV infection that has debilitating effects on quality of life. While there has been a comprehensive evaluation of the prevalence of neuropathic signs/symptoms and risk factors (RFs) for PN or symptomatic PN (SPN) with initiation of combination antiretroviral therapy (cART) in ART-naïve patients, similar evaluation in ART-experienced patients is limited. This study investigated the prevalence and RFs for PN/SPN in ART-experienced patients enrolled in clinical salvage therapy studies. Between February 2000 and June 2007, 522 ART-experienced participants who experienced virologic failure with a prior regimen and started new regimens were followed longitudinally and annually screened for signs and symptoms of PN. Rates of PN/SPN at 3 years since parent study entry were 52.8 and 24.0 %, respectively. Aging, taller height, protease inhibitor use, and female sex were significant RFs for PN/SPN. The use of statin drugs was significantly associated with lower odds of SPN, and it may prevent progression from no SPN to SPN.

Keywords

Peripheral neuropathy Symptomatic peripheral neuropathy Risk factors HIV infection 

Notes

Acknowledgments

This work was supported by National Institute of Health (NIH) grants including the Neurologic AIDS Research Consortium grant NS32228 from NINDS, the AIDS Clinical Trials Grant AI068636 from NIAID, and the Statistical and Data Management Center of the Adult AIDS Clinical Trials Group grant 1 U01 068634. The authors acknowledge the generous dedication of the many participants volunteering for the ALLRT study, and for the contributions of the contributing AIDS Clinical Trials Units, their investigators and staffs, that collected the samples and clinical data used for this analysis. The authors would like to thank reviewers for their thoughtful comments.

Conflict of Interest

Scott R. Evans has grant funding from NIH. The other authors declare that they have no conflict of interest.

References

  1. Bacellar H, Munoz A, Miller EN, Cohen BA, Besley D, Selnes OA, Becker JT, McArthur JC (1994) Temporal trends in the incidence of HIV-1-related neurologic diseases: Multicenter AIDS Cohort Study, 1985–1992. Neurology 44:1892–1900PubMedCrossRefGoogle Scholar
  2. Banerjee S, McCutchan JA, Ances BM, Deutsch R, Riggs PK, Way L, Ellis RJ (2011) Hypertriglyceridemia in combination antiretroviral-treated HIV-positive individuals: potential impact on HIV sensory polyneuropathy. AIDS 25(2):F1–6PubMedCentralPubMedCrossRefGoogle Scholar
  3. Clifford DB, Smurzynski M, Park LS, Yeh TM, Zhao Y, Blair L, Arens M, Evans SR (2009) Effects of active HCV replication on neurologic status in HIV RNA virally suppressed patients. Neurology 73:309–14PubMedCentralPubMedCrossRefGoogle Scholar
  4. Collier AC, Tierney C, Downey GF, Eshleman SH, Kashuba A, Klingman K, Vergis EN, Pakes GE, Rooney JF, Rinehart A, Mellors JW, AIDS Clinical Trials Group Protocol A5143 Team (2008) Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV. HIV Clin Trials 9(2):91–102PubMedCrossRefGoogle Scholar
  5. Cornblath DR, McArthur JC (1988) Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 38:794–796PubMedCrossRefGoogle Scholar
  6. Coulson WF (2011) Statin neuropathy? J Fam Pract 60(4):182–4PubMedGoogle Scholar
  7. Demeter LM, Jiang H, Mukherjee AL, Morse GD, DiFrancesco R, DiCenzo R, Dykes C, Sista P, Bacheler L, Klingman K, Rinehart A, Albrecht M (2009) A randomized trial of therapeutic drug monitoring of protease inhibitors in antiretroviral-experienced, HIV-1-infected patients. AIDS 23(3):357–68PubMedCentralPubMedCrossRefGoogle Scholar
  8. Ellis R, Evans SR, Clifford D, Moo LR, McArthur JC, Collier AC, Benson C, Bosch R, Simpson D, Yiannoutsos CT, Yang Y, Robertson K, Neurological AIDS Research Consortium; AIDS Clinical Trials Group Study Teams A5001 and A362 (2005) Clinical Validation of the Neuroscreen. J Neurovirol 11(6):503–511PubMedCrossRefGoogle Scholar
  9. Ellis RJ, Marquie-Beck J, Delaney P, Alexander T, Clifford DB, McArthur JC, Simpson DM, Ake C, Collier AC, Gelman BB, McCutchan JA, Morgello S, Grant I, CHARTER Group (2008) Human immunodeficiency virus protease inhibitors and risk for peripheral neuropathy. AnnNeurol 64:566–572Google Scholar
  10. Ellis RJ, Rosario D, Clifford DB, McArthur JC, Simpson D, Alexander T, Gelman BB, Vaida F, Collier A, Marra CM, Ances B, Atkinson JH, Dworkin RH, Morgello S, Grant I, CHARTER Study Group (2010) Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER Study. Arch Neurol 67(5):552–8PubMedCrossRefGoogle Scholar
  11. Eron JJ Jr, Park JG, Haubrich R, Aweeka F, Bastow B, Pakes GE, Yu S, Wu H, Richman DD, ACTG5126 Study Team (2009) Predictive value of pharmacokinetics-adjusted phenotypic susceptibility on response to ritonavir-enhanced protease inhibitors (PIs) in human immunodeficiency virus-infected subjects failing prior PI therapy. Antimicrob Agents Chemother 53(6):2335–41PubMedCentralPubMedCrossRefGoogle Scholar
  12. Evans S, Li L (2005) A comparison of goodness of fit tests for the logistic GEE model. Statis Med 24:1245–1261CrossRefGoogle Scholar
  13. Evans SR, Ellis RJ, Chen H, Yeh T, Lee AJ, Schifitto G, Wu K, Bosch RJ, McArthur JC, Simpson DM, Clifford DB (2011) Peripheral neuropathy in HIV: prevalence and risk factors. AIDS 25:919–928PubMedCentralPubMedCrossRefGoogle Scholar
  14. Evans SR, Lee AJ, Ellis RJ, Chen H, Wu K, Bosch RJ, Clifford DB (2012) HIV peripheral neuropathy progression: protection with glucose-lowering drugs? J Neurovirol 18(5):428–433PubMedCentralPubMedCrossRefGoogle Scholar
  15. Fischl MA, Ribaudo HJ, Collier AC, Erice A, Giuliano M, Dehlinger M, Eron JJ Jr, Saag MS, Hammer SM, Vella S, Morse GD, Feinberg JE, Demeter LM, Eshleman SH, Adult AIDS Clinical Trials Group 388 Study Team (2003) A randomized trial of 2 different 4-drug antiretroviral regimens versus a 3-drug regimen, in advanced human immunodeficiency virus disease. J Infect Dis 188(5):625–34, Erratum in: J Infect Dis 188(7):1083PubMedCrossRefGoogle Scholar
  16. Gulick RM, Su Z, Flexner C, Hughes MD, Skolnik PR, Wilkin TJ, Gross R, Krambrink A, Coakley E, Greaves WL, Zolopa A, Reichman R, Godfrey C, Hirsch M, Kuritzkes DR, AIDS Clinical Trials Group 5211 Team (2007) Phase 2 study of the safety and efficacy of Vicriviroc, a CCR5 inhibitor, in HIV-1-infected, treatment-experienced patients: AIDS Clinical Trials Group 5211. J Infect Dis 196(2):304–312PubMedCrossRefGoogle Scholar
  17. Hahn K, Robinson B, Anderson C, Li W, Pardo CA, Morgello S, Simpson D, Nath A (2008) Differential effects of HIV infected macrophages on dorsal root ganglia neurons and axons. Exp Neurol 210(1):30–40PubMedCentralPubMedCrossRefGoogle Scholar
  18. Hammer SM, Vaida F, Bennett KK, Holohan MK, Sheiner L, Eron JJ, Wheat LJ, Mitsuyasu RT, Gulick RM, Valentine FT, Aberg JA, Rogers MD, Karol CN, Saah AJ, Lewis RH, Bessen LJ, Brosgart C, DeGruttola V, Mellors JW, AIDS Clinical Trials Group 398 Study Team (2002) Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial. JAMA 288(2):169–180PubMedCrossRefGoogle Scholar
  19. Huang XS, Zhao SP, Bai L, Hu M, Zhao W, Zhang Q (2009) Atorvastatin and fenofibrate increase apolipoprotein AV and decrease triglycerides by up-regulating peroxisome proliferator-activated receptor-alpha. Br J Pharmacol 158(3):706–12PubMedCentralPubMedCrossRefGoogle Scholar
  20. Keswani SC, Pardo CA, Cherry CL, Hoke A, McArthur JC (2002) HIV-associated sensory neuropathies. AIDS 16:2105–2117PubMedCrossRefGoogle Scholar
  21. McArthur JC, Brew BJ, Nath A (2005) Neurological complications of HIV infection. Lancet Neurol 4:543–555PubMedCrossRefGoogle Scholar
  22. Murphy RL, Gulick RM, DeGruttola V, D'Aquila RT, Eron JJ, Sommadossi JP, Currier JS, Smeaton L, Frank I, Caliendo AM, Gerber JG, Tung R, Kuritzkes DR (1999) Treatment with amprenavir alone or amprenavir with zidovudine and lamivudine in adults with human immunodeficiency virus infection. AIDS Clinical Trials Group 347 Study Team. J Infect Dis 179(4):808–16PubMedCrossRefGoogle Scholar
  23. Otruba P, Kanovsky P, Hlustik P (2011) Treatment with statins and peripheral neuropathy: results of 36-months a prospective clinical and neurophysiological follow-up. Neuro Endocrinol Lett 32(5):688–90PubMedGoogle Scholar
  24. Pardo CA, McArthur JC, Griffin JW (2001) HIV neuropathy: insights in the pathology of HIV peripheral nerve disease. J Peripher Nerv Syst 6(1):21–27PubMedCrossRefGoogle Scholar
  25. Pettersen JA, Jones G, Worthington C, Krentz HB, Keppler OT, Hoke A, Gill MJ, Power C (2006) Sensory neuropathy in human immunodeficiency virus/acquired immunodeficiency syndrome patients: protease inhibitor-mediated neurotoxicity. AnnNeurol 59:816–824Google Scholar
  26. Purwata TE (2011) High TNF-alpha plasma levels and macrophages iNOS and TNF-alpha expression as risk factors for painful diabetic neuropathy. J Pain Res 4:169–175PubMedCentralPubMedCrossRefGoogle Scholar
  27. Schönbeck U, Libby P (2004) Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents? Circulation 109(21 Suppl 1):II18–26PubMedGoogle Scholar
  28. Simpson DM, Kitch D, Evans SR, McArthur JC, Asmuth DM, Cohen B, Goodkin K, Gerschenson M, So Y, Marra CM, Diaz-Arrastia R, Shriver S, Millar L, Clifford DB, ACTG A5117 Study Group (2006) HIV Neuropathy Natural History Cohort Study: Assessment Measures and Risk Factors. Neurology 66:1679–1687PubMedCrossRefGoogle Scholar
  29. Sosenko JM, Boulton AJM, Gadia MT, Ward JD, Skylar JS (1988) The association between symptomatic sensory neuropathy and body stature in diabetic patients. Diabetes Res Clin Pract 4:95–98PubMedCrossRefGoogle Scholar
  30. Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH, EURODIAB Prospective Complications Study Group (2005) Vascular risk factors and diabetic neuropathy. N Engl J Med 352(4):341–50PubMedCrossRefGoogle Scholar
  31. Tierney EF, Thurman DJ, Beckles GL, Cadwell BL (2013) Association of statin use with peripheral neuropathy in the US population 40 years of age or older. J Diabetes 5(2):207–15PubMedCrossRefGoogle Scholar
  32. Wilkin TJ, Su Z, Kuritzkes DR, Hughes M, Flexner C, Gross R, Coakley E, Greaves W, Godfrey C, Skolnik PR, Timpone J, Rodriguez B, Gulick RM (2007) HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trials Group A5211. Clin Infect Dis 44(4):591–595PubMedCrossRefGoogle Scholar
  33. Wulff EA, Wang AK, Simpson DM (2000) HIV-associated peripheral neuropathy: Epidemiology, pathophysiology and treatment. Drugs 59:1251–1260PubMedCrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2013

Authors and Affiliations

  • Huichao Chen
    • 1
  • David B. Clifford
    • 2
  • Lijuan Deng
    • 1
  • Kunling Wu
    • 1
  • Anthony J. Lee
    • 1
  • Ronald J. Bosch
    • 1
  • Sharon A. Riddler
    • 3
  • Ronald J. Ellis
    • 4
  • Scott R. Evans
    • 1
  1. 1.Harvard School of Public HealthBostonUSA
  2. 2.Washington UniversitySaint LouisUSA
  3. 3.University of PittsburghPittsburghUSA
  4. 4.University of California at San DiegoSan DiegoUSA

Personalised recommendations