Skip to main content

Advertisement

SpringerLink
Log in

Neuromuscular complications in HIV: effects of aging

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

There has been speculation that chronic HIV infection is a condition of accelerated aging that may lead to early onset of disease in multiple organ systems. The neuromuscular disorders of HIV, in particular distal symmetric polyneuropathy and myopathies, are also seen in the general population among older patients. As the HIV-infected population ages, there may be deleterious synergistic effects of age and chronic HIV infection on the brain, peripheral nerve, and muscle. In this review, we explore commonalities between the clinical features and putative mechanisms of neuromuscular disorders and HIV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bernatsky S, Joseph L, Pineau CA, Belisle P, Boivin JF, Banerjee D et al (2009) Estimating the prevalence of polymyositis and dermatomyositis from administrative data: age, sex and regional differences. Ann Rheum Dis 68:1192–1196

    Article  PubMed  CAS  Google Scholar 

  • Bestilny LJ, Gill MJ, Mody CH, Riabowol KT (2000) Accelerated replicative senescence of the peripheral immune system induced by HIV infection. AIDS 14:771–780

    Article  PubMed  CAS  Google Scholar 

  • Boirie Y (2009) Physiopathological mechanism of sarcopenia. J Nutr Health Aging 13:717–723

    Article  PubMed  CAS  Google Scholar 

  • Bouche P, Cattelin F, Saint-Jean O, Leger JM, Queslati S, Guez D et al (1993) Clinical and electrophysiological study of the peripheral nervous system in the elderly. J Neurol 240:263–268

    Article  PubMed  CAS  Google Scholar 

  • Brinkman K, ter Hofstede HJ, Burger DM, Smeitink JA, Koopmans PP (1998) Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 12:1735–1744

    Article  PubMed  CAS  Google Scholar 

  • Brinley FJ Jr, Pardo CA, Verma A (2001) Human immunodeficiency virus and the peripheral nervous system workshop. Arch Neurol 58:1561–1566

    Article  PubMed  Google Scholar 

  • Brunk UT, Terman A (2002) The mitochondrial–lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem 269:1996–2002

    Article  PubMed  CAS  Google Scholar 

  • Buffet M, Schwarzinger M, Amellal B, Gourlain K, Bui P, Prevot M et al (2005) Mitochondrial DNA depletion in adipose tissue of HIV-infected patients with peripheral lipoatrophy. J Clin Virol 33:60–64

    Article  PubMed  CAS  Google Scholar 

  • Bujalska IJ, Kumar S, Stewart PM (1997) Does central obesity reflect “Cushing’s disease of the omentum”? Lancet 349:1210–1213

    Article  PubMed  CAS  Google Scholar 

  • Cao W, Jamieson BD, Hultin LE, Hultin PM, Effros RB, Detels R (2009) Premature aging of T cells is associated with faster HIV-1 disease progression. J Acquir Immune Defic Syndr 50:137–147

    Article  PubMed  Google Scholar 

  • Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ et al (1998) A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 12:F51–8

    Article  PubMed  CAS  Google Scholar 

  • Cavanagh JB (1964) The significance of the “dying back” process in experimental and human neurological disease. Int Rev Exp Pathol 3:219–267

    PubMed  CAS  Google Scholar 

  • Chen CH, Cheng YC (1989) Delayed cytotoxicity and selective loss of mitochondrial DNA in cells treated with the anti-human immunodeficiency virus compound 2′,3′-dideoxycytidine. J Biol Chem 264:11934–11937

    PubMed  CAS  Google Scholar 

  • Childs EA, Lyles RH, Selnes OA, Chen B, Miller EN, Cohen BA et al (1999) Plasma viral load and CD4 lymphocytes predict HIV-associated dementia and sensory neuropathy. Neurology 52:607–613

    Article  PubMed  CAS  Google Scholar 

  • Chow DC, Wood R, Grandinetti A, Shikuma C, Schatz I, Low P (2006) Cardiovagal autonomic dysfunction in relation to HIV-associated lipodystrophy. HIV Clin Trials 7:16–23

    Article  PubMed  Google Scholar 

  • Christou DD, Jones PP, Pimentel AE, Seals DR (2004) Increased abdominal-to-peripheral fat distribution contributes to altered autonomic–circulatory control with human aging. Am J Physiol Heart Circ Physiol 287:H1530–7

    Article  PubMed  CAS  Google Scholar 

  • Cohen JA, Laudenslager M (1989) Autonomic nervous system involvement in patients with human immunodeficiency virus infection. Neurology 39:1111–1112

    Article  PubMed  CAS  Google Scholar 

  • Compostella C, Compostella L, D’Elia R (2008) The symptoms of autonomic dysfunction in HIV-positive Africans. Clin Auton Res 18:6–12

    Article  PubMed  Google Scholar 

  • Coodley GO, Loveless MO, Nelson HD, Coodley MK (1994a) Endocrine function in the HIV wasting syndrome. J Acquir Immune Defic Syndr 7:46–51

    PubMed  CAS  Google Scholar 

  • Coodley GO, Loveless MO, Merrill TM (1994b) The HIV wasting syndrome: a review. J Acquir Immune Defic Syndr 7:681–694

    PubMed  CAS  Google Scholar 

  • Cornblath DR, Hoke A (2006) Recent advances in HIV neuropathy. Curr Opin Neurol 19:446–450

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Deeks SG (2011) HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med 62:141–155

    Article  PubMed  CAS  Google Scholar 

  • Ellis RJ, Rosario D, Clifford DB, McArthur JC, Simpson D, Alexander T et al (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 67:552–558

    Article  PubMed  Google Scholar 

  • Evans SR, Ellis RJ, Chen H, Yeh TM, Lee AJ, Schifitto G et al (2011) Peripheral neuropathy in HIV: prevalence and risk factors. AIDS 25(7):919–928

    Article  PubMed  Google Scholar 

  • Fagnoni FF, Vescovini R, Passeri G, Bologna G, Pedrazzoni M, Lavagetto G et al (2000) Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood 95:2860–2868

    PubMed  CAS  Google Scholar 

  • Falutz J, Potvin D, Mamputu JC, Assaad H, Zoltowska M, Michaud SE et al (2010) Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. J Acquir Immune Defic Syndr 53:311–322

    Article  PubMed  CAS  Google Scholar 

  • Fliers E, Kreier F, Voshol PJ, Havekes LM, Sauerwein HP, Kalsbeek A et al (2003a) White adipose tissue: getting nervous. J Neuroendocrinol 15:1005–1010

    Article  PubMed  CAS  Google Scholar 

  • Fliers E, Sauerwein HP, Romijn JA, Reiss P, van der Valk M, Kalsbeek A et al (2003b) HIV-associated adipose redistribution syndrome as a selective autonomic neuropathy. Lancet 362:1758–1760

    Article  PubMed  CAS  Google Scholar 

  • Freeman R, Roberts MS, Friedman LS, Broadbridge C (1990) Autonomic function and human immunodeficiency virus infection. Neurology 40:575–580

    Article  PubMed  CAS  Google Scholar 

  • Gan SK, Samaras K, Thompson CH, Kraegen EW, Carr A, Cooper DA et al (2002) Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy. Diabetes 51:3163–3169

    Article  PubMed  CAS  Google Scholar 

  • Giunta B, Fernandez F, Nikolic WV, Obregon D, Rrapo E, Town T et al (2008) Inflammaging as a prodrome to Alzheimer's disease. J Neuroinflammation 5:51

    Article  PubMed  Google Scholar 

  • Goransson LG, Mellgren SI, Lindal S, Omdal R (2004) The effect of age and gender on epidermal nerve fiber density. Neurology 62:774–777

    Article  PubMed  CAS  Google Scholar 

  • Harman D (2001) Aging: overview. Ann N Y Acad Sci 928:1–21

    Article  PubMed  CAS  Google Scholar 

  • Harpaz R, Ortega-Sanchez IR, Seward JF, Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC) (2008) Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 57:1–30, quiz CE2-4

    PubMed  Google Scholar 

  • Heckmann JM, Pillay K, Hearn AP, Kenyon C (2010) Polymyositis in African HIV-infected subjects. Neuromuscul Disord 20:735–739

    Article  PubMed  CAS  Google Scholar 

  • Herrmann DN, McDermott MP, Sowden JE, Henderson D, Messing S, Cruttenden K et al (2006) Is skin biopsy a predictor of transition to symptomatic HIV neuropathy? A longitudinal study. Neurology 66:857–861

    Article  PubMed  CAS  Google Scholar 

  • Hofhaus G, Berneburg M, Wulfert M, Gattermann N (2003) Live now—pay by ageing: high performance mitochondrial activity in youth and its age-related side effects. Exp Physiol 88:167–174

    Article  PubMed  CAS  Google Scholar 

  • Illa I, Nath A, Dalakas M (1991) Immunocytochemical and virological characteristics of HIV-associated inflammatory myopathies: similarities with seronegative polymyositis. Ann Neurol 29:474–481

    Article  PubMed  CAS  Google Scholar 

  • Jacobs JM, Love S (1985) Qualitative and quantitative morphology of human sural nerve at different ages. Brain 108(Pt 4):897–924

    Article  PubMed  Google Scholar 

  • Johnson RW, Williams FM, Kazi S, Dimachkie MM, Reveille JD (2003) Human immunodeficiency virus-associated polymyositis: a longitudinal study of outcome. Arthritis Rheum 49:172–178

    Article  PubMed  Google Scholar 

  • Keswani SC, Polley M, Pardo CA, Griffin JW, McArthur JC, Hoke A (2003) Schwann cell chemokine receptors mediate HIV-1 gp120 toxicity to sensory neurons. Ann Neurol 54:287–296

    Article  PubMed  CAS  Google Scholar 

  • Lebech AM, Kristoffersen US, Mehlsen J, Wiinberg N, Petersen CL, Hesse B et al (2007) Autonomic dysfunction in HIV patients on antiretroviral therapy: studies of heart rate variability. Clin Physiol Funct Imaging 27:363–367

    Article  PubMed  Google Scholar 

  • Lehmann HC, Chen W, Borzan J, Mankowski JL, Hoke A (2011) Mitochondrial dysfunction in distal axons contributes to human immunodeficiency virus sensory neuropathy. Ann Neurol 69:100–110

    Article  PubMed  CAS  Google Scholar 

  • Lichtenstein KA, Armon C, Baron A, Moorman AC, Wood KC, Holmberg SD et al (2005) Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort. Clin Infect Dis 40:148–157

    Article  PubMed  Google Scholar 

  • Lihn AS, Richelsen B, Pedersen SB, Haugaard SB, Rathje GS, Madsbad S et al (2003) Increased expression of TNF-alpha, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels. Am J Physiol Endocrinol Metab 285:E1072–80

    PubMed  CAS  Google Scholar 

  • Low PA, Denq JC, Opfer-Gehrking TL, Dyck PJ, O’Brien PC, Slezak JM (1997) Effect of age and gender on sudomotor and cardiovagal function and blood pressure response to tilt in normal subjects. Muscle Nerve 20:1561–1568

    Article  PubMed  CAS  Google Scholar 

  • Low PA, Benrud-Larson LM, Sletten DM, Opfer-Gehrking TL, Weigand SD, O'Brien PC et al (2004) Autonomic symptoms and diabetic neuropathy: a population-based study. Diabetes Care 27:2942–2947

    Article  PubMed  Google Scholar 

  • Luzi L, Perseghin G, Tambussi G, Meneghini E, Scifo P, Pagliato E et al (2003) Intramyocellular lipid accumulation and reduced whole body lipid oxidation in HIV lipodystrophy. Am J Physiol Endocrinol Metab 284:E274–80

    PubMed  CAS  Google Scholar 

  • McArthur JC, Brew BJ, Nath A (2005) Neurological complications of HIV infection. Lancet Neurol 4:543–555

    Article  PubMed  Google Scholar 

  • Melli G, Keswani SC, Fischer A, Chen W, Hoke A (2006) Spatially distinct and functionally independent mechanisms of axonal degeneration in a model of HIV-associated sensory neuropathy. Brain 129:1330–1338

    Article  PubMed  Google Scholar 

  • Mittal CM, Wig N, Mishra S, Deepak KK (2004) Heart rate variability in human immunodeficiency virus-positive individuals. Int J Cardiol 94:1–6

    Article  PubMed  Google Scholar 

  • Morgello S, Wolfe D, Godfrey E, Feinstein R, Tagliati M, Simpson DM (1995) Mitochondrial abnormalities in human immunodeficiency virus-associated myopathy. Acta Neuropathol 90:366–374

    Article  PubMed  CAS  Google Scholar 

  • Morgello S, Estanislao L, Simpson D, Geraci A, DiRocco A, Gerits P et al (2004) HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy: the Manhattan HIV Brain Bank. Arch Neurol 61:546–551

    Article  PubMed  Google Scholar 

  • Negoro S, Hara H, Miyata S, Saiki O, Tanaka T, Yoshizaki K et al (1986) Mechanisms of age-related decline in antigen-specific T cell proliferative response: IL-2 receptor expression and recombinant IL-2 induced proliferative response of purified Tac-positive T cells. Mech Ageing Dev 36:223–241

    Article  PubMed  CAS  Google Scholar 

  • Ng AV, Callister R, Johnson DG, Seals DR (1993) Age and gender influence muscle sympathetic nerve activity at rest in healthy humans. Hypertension 21:498–503

    Article  PubMed  CAS  Google Scholar 

  • Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD et al (2005) A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 352:2271–2284

    Article  PubMed  CAS  Google Scholar 

  • Pacenti M, Barzon L, Favaretto F, Fincati K, Romano S, Milan G et al (2006) Microarray analysis during adipogenesis identifies new genes altered by antiretroviral drugs. AIDS 20:1691–1705

    Article  PubMed  CAS  Google Scholar 

  • Pletz MW, Duda PW, Kappos L, Steck AJ (2003) Immune-mediated neuropathies: etiology and pathogenic relationship to aging processes. J Neuroimmunol 137:1–11

    Article  PubMed  CAS  Google Scholar 

  • Prelog M (2006) Aging of the immune system: a risk factor for autoimmunity? Autoimmun Rev 5:136–139

    Article  PubMed  CAS  Google Scholar 

  • Quattrini C, Harris ND, Malik RA, Tesfaye S (2007) Impaired skin microvascular reactivity in painful diabetic neuropathy. Diabetes Care 30:655–659

    Article  PubMed  Google Scholar 

  • Rance NE, McArthur JC, Cornblath DR, Landstrom DL, Griffin JW, Price DL (1988) Gracile tract degeneration in patients with sensory neuropathy and AIDS. Neurology 38:265–271

    Article  PubMed  CAS  Google Scholar 

  • Rowan AJ, Ramsay RE, Collins JF, Pryor F, Boardman KD, Uthman BM et al (2005) New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology 64:1868–1873

    Article  PubMed  CAS  Google Scholar 

  • Said G, Lacroix C, Chemouilli P, Goulon-Goeau C, Roullet E, Penaud D et al (1991) Cytomegalovirus neuropathy in acquired immunodeficiency syndrome: a clinical and pathological study. Ann Neurol 29:139–146

    Article  PubMed  CAS  Google Scholar 

  • Sakhuja A, Goyal A, Jaryal AK, Wig N, Vajpayee M, Kumar A et al (2007) Heart rate variability and autonomic function tests in HIV positive individuals in India. Clin Auton Res 17:193–196

    Article  PubMed  Google Scholar 

  • Sathekge M, Maes A, Kgomo M, Stolz A, Ankrah A, Van de Wiele C (2010) Evaluation of glucose uptake by skeletal muscle tissue and subcutaneous fat in HIV-infected patients with and without lipodystrophy using FDG-PET. Nucl Med Commun 31:311–314

    Article  PubMed  CAS  Google Scholar 

  • Schifitto G, McDermott MP, McArthur JC, Marder K, Sacktor N, Epstein L et al (2002) Incidence of and risk factors for HIV-associated distal sensory polyneuropathy. Neurology 58:1764–1768

    Article  PubMed  CAS  Google Scholar 

  • Schrager MA, Metter EJ, Simonsick E, Ble A, Bandinelli S, Lauretani F et al (2007) Sarcopenic obesity and inflammation in the InCHIANTI study. J Appl Physiol 102:919–925

    Article  PubMed  Google Scholar 

  • Scruggs ER, Dirks Naylor AJ (2008) Mechanisms of zidovudine-induced mitochondrial toxicity and myopathy. Pharmacology 82:83–88

    Article  PubMed  CAS  Google Scholar 

  • Simanek AM, Dowd JB, Pawelec G, Melzer D, Dutta A, Aiello AE (2011) Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States. PLoS One 6:e16103

    Article  PubMed  CAS  Google Scholar 

  • Simpson DM, Bender AN (1988) Human immunodeficiency virus-associated myopathy: analysis of 11 patients. Ann Neurol 24:79–84

    Article  PubMed  CAS  Google Scholar 

  • Simpson DM, Bender AN, Farraye J, Mendelson SG, Wolfe DE (1990) Human immunodeficiency virus wasting syndrome may represent a treatable myopathy. Neurology 40:535–538

    Article  PubMed  CAS  Google Scholar 

  • Simpson DM, Kitch D, Evans SR, McArthur JC, Asmuth DM, Cohen B et al (2006) HIV neuropathy natural history cohort study: assessment measures and risk factors. Neurology 66:1679–1687

    Article  PubMed  CAS  Google Scholar 

  • Simpson DM, Brown S, Tobias J (2008) NGX-4010 C107 Study Group. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology 70:2305–2313

    Article  PubMed  CAS  Google Scholar 

  • Skrapari I, Tentolouris N, Perrea D, Bakoyiannis C, Papazafiropoulou A, Katsilambros N (2007) Baroreflex sensitivity in obesity: relationship with cardiac autonomic nervous system activity. Obesity (Silver Spring) 15:1685–1693

    Article  Google Scholar 

  • Torriani M, Thomas BJ, Barlow RB, Librizzi J, Dolan S, Grinspoon S (2006) Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution. J Appl Physiol 100:609–614

    Article  PubMed  Google Scholar 

  • Umapathi T, Tan WL, Tan NC, Chan YH (2006) Determinants of epidermal nerve fiber density in normal individuals. Muscle Nerve 33:742–746

    Article  PubMed  CAS  Google Scholar 

  • Van Gaal LF, Mertens IL, De Block CE (2006) Mechanisms linking obesity with cardiovascular disease. Nature 444:875–880

    Article  PubMed  Google Scholar 

  • Vance DE, Mugavero M, Willig J, Raper JL, Saag MS (2011) Aging with HIV: a cross-sectional study of comorbidity prevalence and clinical characteristics across decades of life. J Assoc Nurses AIDS Care 22:17–25

    Article  PubMed  Google Scholar 

  • Vrancken AF, Franssen H, Wokke JH, Teunissen LL, Notermans NC (2002) Chronic idiopathic axonal polyneuropathy and successful aging of the peripheral nervous system in elderly people. Arch Neurol 59:533–540

    Article  PubMed  Google Scholar 

  • Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21:697–738

    Article  PubMed  CAS  Google Scholar 

  • Yarasheski KE, Scherzer R, Kotler DP, Dobs AS, Tien PC, Lewis CE et al (2011) Age-related skeletal muscle decline is similar in HIV-infected and uninfected individuals. J Gerontol A Biol Sci Med Sci 66:332–340

    Article  PubMed  Google Scholar 

  • Zhou L, Kitch DW, Evans SR, Hauer P, Raman S, Ebenezer GJ et al (2007) Correlates of epidermal nerve fiber densities in HIV-associated distal sensory polyneuropathy. Neurology 68:2113–2119

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1052, New York, NY, 10029, USA

    Jessica Robinson-Papp & David M. Simpson

  2. Department of Neurology, John Hopkins Medicine, 600 N Wolfe Street, Pathology 627 C, Baltimore, MD, 21287, USA

    Ik Lin Tan

Authors
  1. Jessica Robinson-Papp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ik Lin Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David M. Simpson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jessica Robinson-Papp.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Robinson-Papp, J., Tan, I.L. & Simpson, D.M. Neuromuscular complications in HIV: effects of aging. J. Neurovirol. 18, 331–338 (2012). https://doi.org/10.1007/s13365-011-0074-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-011-0074-x

Keywords

Search

Navigation