Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy

The CHARTER study

Ronald J. Ellis, Debralee Rosario, David B. Clifford, Justin C. McArthur, David Simpson, Terry Alexander, Benjamin Gelman, Florin Vaida, Ann Collier, Christina M. Marra, Beau Ances, J. Hampton Atkinson, Robert H. Dworkin, Susan Morgello, Igor Grant

Research output: Contribution to journalArticle

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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. Design: 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. Setting: Six US academic medical centers. Patients: One thousand five hundred thirty-nine HIV-infected individuals enrolled in the CNS (Central Nervous System) HIV Anti-Retroviral Therapy Effects Research study. Main Outcome Measures: 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.

Original languageEnglish (US)
Pages (from-to)552-558
Number of pages7
JournalArchives of Neurology
Volume67
Issue number5
DOIs
StatePublished - May 2010

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HIV
Neuralgia
Therapeutics
Quality of Life
AIDS/HIV
Antiretroviral Therapy
Dideoxynucleosides
Outcome Assessment (Health Care)
Social Adjustment
Unemployment
Virus Diseases
Vibration
Pain
Health Surveys
Viral Load
Ankle
Hepacivirus
Pharmaceutical Preparations
Reflex
Foot

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy : The CHARTER study. / Ellis, Ronald J.; Rosario, Debralee; Clifford, David B.; McArthur, Justin C.; Simpson, David; Alexander, Terry; Gelman, Benjamin; Vaida, Florin; Collier, Ann; Marra, Christina M.; Ances, Beau; Atkinson, J. Hampton; Dworkin, Robert H.; Morgello, Susan; Grant, Igor.

In: Archives of Neurology, Vol. 67, No. 5, 05.2010, p. 552-558.

Research output: Contribution to journalArticle

Ellis, RJ, Rosario, D, Clifford, DB, McArthur, JC, Simpson, D, Alexander, T, Gelman, B, Vaida, F, Collier, A, Marra, CM, Ances, B, Atkinson, JH, Dworkin, RH, Morgello, S & Grant, I 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', Archives of Neurology, vol. 67, no. 5, pp. 552-558. https://doi.org/10.1001/archneurol.2010.76
Ellis, Ronald J. ; Rosario, Debralee ; Clifford, David B. ; McArthur, Justin C. ; Simpson, David ; Alexander, Terry ; Gelman, Benjamin ; Vaida, Florin ; Collier, Ann ; Marra, Christina M. ; Ances, Beau ; Atkinson, J. Hampton ; Dworkin, Robert H. ; Morgello, Susan ; Grant, Igor. / Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy : The CHARTER study. In: Archives of Neurology. 2010 ; Vol. 67, No. 5. pp. 552-558.
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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. Design: 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. Setting: Six US academic medical centers. Patients: One thousand five hundred thirty-nine HIV-infected individuals enrolled in the CNS (Central Nervous System) HIV Anti-Retroviral Therapy Effects Research study. Main Outcome Measures: 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.",
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T1 - Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy

T2 - The CHARTER study

AU - Ellis, Ronald J.

AU - Rosario, Debralee

AU - Clifford, David B.

AU - McArthur, Justin C.

AU - Simpson, David

AU - Alexander, Terry

AU - Gelman, Benjamin

AU - Vaida, Florin

AU - Collier, Ann

AU - Marra, Christina M.

AU - Ances, Beau

AU - Atkinson, J. Hampton

AU - Dworkin, Robert H.

AU - Morgello, Susan

AU - Grant, Igor

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N2 - 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. Design: 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. Setting: Six US academic medical centers. Patients: One thousand five hundred thirty-nine HIV-infected individuals enrolled in the CNS (Central Nervous System) HIV Anti-Retroviral Therapy Effects Research study. Main Outcome Measures: 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.

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