Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER Study.
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.
Ellis
Ronald J
RJ
HIV Neurobehavioral Research Center, Department of Neurosciences, University of California, San Diego, San Diego, CA 92103, USA. roellis@ucsd.edu
Rosario
Debralee
D
Clifford
David B
DB
McArthur
Justin C
JC
Simpson
David
D
Alexander
Terry
T
Gelman
Benjamin B
BB
Vaida
Florin
F
Collier
Ann
A
Marra
Christina M
CM
Ances
Beau
B
Atkinson
J Hampton
JH
Dworkin
Robert H
RH
Morgello
Susan
S
Grant
Igor
I
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
D044966:Anti-Retroviral Agents
J Infect Dis. 2005 Sep 15;192(6):974-83
16107949
Br J Psychiatry. 1991 Nov;159:645-53, 658
1756340
Gerontologist. 1969 Autumn;9(3):179-86
5349366
J Pers Assess. 1996 Dec;67(3):588-97
8991972
AIDS. 2006 Jul 13;20(11):1503-13
16847405
J Neurovirol. 2002 Dec;8 Suppl 2:115-21
12491162
Ann Neurol. 2006 May;59(5):816-24
16634006
AIDS. 1997 Oct;11(12):F101-5
9342061
Eur J Neurol. 2004 Feb;11(2):97-102
14748769
Ann Neurol. 2008 Nov;64(5):566-72
19067367
Neurology. 2006 Jun 13;66(11):1679-87
16769940
Suppl Clin Neurophysiol. 2004;57:195-210
16106620
J Clin Virol. 2003 Feb;26(2):195-207
12600651
Neurology. 1988 May;38(5):794-6
2834669
JAMA. 2008 Aug 6;300(5):555-70
18677028
AIDS Res Hum Retroviruses. 2008 Aug;24(8):1027-30
18724802
HIV Med. 2008 Oct;9(9):731-7
18651859
AIDS. 2000 Feb 18;14(3):273-8
10716503
Arch Neurol. 1999 Jan;56(1):84-9
9923765
Neurology. 2006 Mar 28;66(6):867-73
16567704
AIDS. 2002 Feb 15;16(3):407-12
11834952
Clin Infect Dis. 2005 Jan 1;40(1):148-57
15614705
HIV Med. 2003 Jul;4(3):255-62
12859325
J Int Neuropsychol Soc. 2004 May;10(3):317-31
15147590
Qual Life Res. 1997 Aug;6(6):481-93
9330549
Science. 1997 Jul 4;277(5322):112-6
9204894
J Neurovirol. 2005 Dec;11(6):503-11
16338744
Ann Intern Med. 1992 Jan 15;116(2):129-37
1727616
AIDS. 2000 Mar 31;14(5):615
10780724
AIDS. 2005 Oct;19 Suppl 3:S135-9
16251810
Curr Opin Neurol. 2006 Oct;19(5):446-50
16969153
Neurology. 1999 Feb;52(3):607-13
10025796
Curr Infect Dis Rep. 2004 Jun;6(3):237-242
15142488