title: Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER Study.
abstract: OBJECTIVE
  To provide updated estimates of the prevalence and clinical impact of human immunodeficiency virus-associated sensory neuropathy (HIV-SN) and neuropathic pain due to HIV-SN in the combination antiretroviral therapy (CART) era.
  
  
  METHODS
  Prospective, cross-sectional analysis. Clinical correlates for HIV-SN and neuropathic pain, including age, exposure to CART, CD4 levels, plasma viral load, hepatitis C virus infection, and alcohol use disorders, were evaluated in univariate and multivariate models.
  
  
  METHODS
  Six US academic medical centers.
  
  
  METHODS
  One thousand five hundred thirty-nine HIV-infected individuals enrolled in the CNS (Central Nervous System) HIV Anti-Retroviral Therapy Effects Research study.
  
  
  METHODS
  The presence of HIV-SN, defined by 1 or more clinical signs (diminished vibration or sharp sensation in the legs and feet; reduced ankle reflexes) in a distal, symmetrical pattern. Neuropathic pain was defined as aching, stabbing, or burning in a similar distribution. The effect on quality of life was assessed with the Medical Outcomes Study HIV Health Survey.
  
  
  RESULTS
  We found HIV-SN in 881 participants. Of these, 38.0% reported neuropathic pain. Neuropathic pain was significantly associated with disability in daily activities, unemployment, and reduced quality of life. Risk factors for HIV-SN after adjustment were advancing age (odds ratio, 2.1 [95% confidence interval, 1.8-2.5] per 10 years), lower CD4 nadir (1.2 [1.1-1.2] per 100-cell decrease), current CART use (1.6 [1.3-2.8]), and past "D-drug" use (specific dideoxynucleoside analogue antiretrovirals) (2.0 [1.3-2.6]). Risk factors for neuropathic pain were past D-drug use and higher CD4 nadir.
  
  
  CONCLUSIONS
  Neuropathic pain and HIV-SN remain prevalent, causing substantial disability and reduced quality of life even with successful CART. The clinical correlates of HIV-SN have changed with the evolution of treatment. These findings argue for redoubled efforts to determine HIV-SN pathogenesis and the development of symptomatic and neuroregenerative therapies.
authors.affiliation: HIV Neurobehavioral Research Center, Department of Neurosciences, University of California, San Diego, San Diego, CA 92103, USA. roellis@ucsd.edu
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Debralee
authors.initials: D
authors.lastname: Rosario
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: David
authors.initials: D
authors.lastname: Simpson
authors.forename: Terry
authors.initials: T
authors.lastname: Alexander
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.forename: Ann
authors.initials: A
authors.lastname: Collier
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.forename: Beau
authors.initials: B
authors.lastname: Ances
authors.forename: J Hampton
authors.initials: JH
authors.lastname: Atkinson
authors.forename: Robert H
authors.initials: RH
authors.lastname: Dworkin
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000437:Alcoholism / Q000453:epidemiology; D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D015897:Comorbidity; D003430:Cross-Sectional Studies; D004651:Employment; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006526:Hepatitis C / Q000453:epidemiology; D006801:Humans; D007121:Immunocompetence / Q000276:immunology; D016867:Immunocompromised Host / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000453:epidemiology* / Q000821:virology; D015995:Prevalence; D011446:Prospective Studies; D011788:Quality of Life; D012307:Risk Factors; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents
references.citation: J Infect Dis. 2005 Sep 15;192(6):974-83
references.pmid: 16107949
references.citation: Br J Psychiatry. 1991 Nov;159:645-53, 658
references.pmid: 1756340
references.citation: Gerontologist. 1969 Autumn;9(3):179-86
references.pmid: 5349366
references.citation: J Pers Assess. 1996 Dec;67(3):588-97
references.pmid: 8991972
references.citation: AIDS. 2006 Jul 13;20(11):1503-13
references.pmid: 16847405
references.citation: J Neurovirol. 2002 Dec;8 Suppl 2:115-21
references.pmid: 12491162
references.citation: Ann Neurol. 2006 May;59(5):816-24
references.pmid: 16634006
references.citation: AIDS. 1997 Oct;11(12):F101-5
references.pmid: 9342061
references.citation: Eur J Neurol. 2004 Feb;11(2):97-102
references.pmid: 14748769
references.citation: Ann Neurol. 2008 Nov;64(5):566-72
references.pmid: 19067367
references.citation: Neurology. 2006 Jun 13;66(11):1679-87
references.pmid: 16769940
references.citation: Suppl Clin Neurophysiol. 2004;57:195-210
references.pmid: 16106620
references.citation: J Clin Virol. 2003 Feb;26(2):195-207
references.pmid: 12600651
references.citation: Neurology. 1988 May;38(5):794-6
references.pmid: 2834669
references.citation: JAMA. 2008 Aug 6;300(5):555-70
references.pmid: 18677028
references.citation: AIDS Res Hum Retroviruses. 2008 Aug;24(8):1027-30
references.pmid: 18724802
references.citation: HIV Med. 2008 Oct;9(9):731-7
references.pmid: 18651859
references.citation: AIDS. 2000 Feb 18;14(3):273-8
references.pmid: 10716503
references.citation: Arch Neurol. 1999 Jan;56(1):84-9
references.pmid: 9923765
references.citation: Neurology. 2006 Mar 28;66(6):867-73
references.pmid: 16567704
references.citation: AIDS. 2002 Feb 15;16(3):407-12
references.pmid: 11834952
references.citation: Clin Infect Dis. 2005 Jan 1;40(1):148-57
references.pmid: 15614705
references.citation: HIV Med. 2003 Jul;4(3):255-62
references.pmid: 12859325
references.citation: J Int Neuropsychol Soc. 2004 May;10(3):317-31
references.pmid: 15147590
references.citation: Qual Life Res. 1997 Aug;6(6):481-93
references.pmid: 9330549
references.citation: Science. 1997 Jul 4;277(5322):112-6
references.pmid: 9204894
references.citation: J Neurovirol. 2005 Dec;11(6):503-11
references.pmid: 16338744
references.citation: Ann Intern Med. 1992 Jan 15;116(2):129-37
references.pmid: 1727616
references.citation: AIDS. 2000 Mar 31;14(5):615
references.pmid: 10780724
references.citation: AIDS. 2005 Oct;19 Suppl 3:S135-9
references.pmid: 16251810
references.citation: Curr Opin Neurol. 2006 Oct;19(5):446-50
references.pmid: 16969153
references.citation: Neurology. 1999 Feb;52(3):607-13
references.pmid: 10025796
references.citation: Curr Infect Dis Rep. 2004 Jun;6(3):237-242
references.pmid: 15142488