Anemia and red blood cell indices predict HIV-associated neurocognitive impairment in the highly active antiretroviral therapy era

Asha R. Kallianpur; Quan Wang; Peilin Jia; Todd Hulgan; Zhongming Zhao; Scott L. Letendre; Ronald J. Ellis; Robert K. Heaton; Donald R. Franklin; Jill Barnholtz-Sloan; Ann C. Collier; Christina M. Marra; David B. Clifford; Benjamin B. Gelman; Justin C. McArthur; Susan Morgello; David M. Simpson; J. A. McCutchan; Igor Grant; J. Allen McCutchan; Thomas D. Marcotte; Donald Franklin; Terry Alexander; Edmund Capparelli; J. Hampton Atkinson; Steven Paul Woods; Matthew Dawson; David M. Smith; Christine Fennema-Notestine; Michael J. Taylor; Rebecca Theilmann; Anthony C. Gamst; Clint Cushman; Ian Abramson; Florin Vaida; Jennifer Marquie-Beck; Vincent Rogalski; David Simpson; Letty Mintz; Will Toperoff; Ann Collier; Christina Marra; Trudy Jones; Benjamin Gelman; Eleanor Head; Muhammad Al-Lozi; Mengesha Teshome

doi:10.1093/infdis/jiv754

Anemia and red blood cell indices predict HIV-associated neurocognitive impairment in the highly active antiretroviral therapy era

Asha R. Kallianpur, Quan Wang, Peilin Jia, Todd Hulgan, Zhongming Zhao, Scott L. Letendre, Ronald J. Ellis, Robert K. Heaton, Donald R. Franklin, Jill Barnholtz-Sloan, Ann C. Collier, Christina M. Marra, David B. Clifford, Benjamin B. Gelman, Justin C. McArthur, Susan Morgello, David M. Simpson, J. A. McCutchan, Igor Grant, J. Allen McCutchanThomas D. Marcotte, Donald Franklin, Terry Alexander, Edmund Capparelli, J. Hampton Atkinson, Steven Paul Woods, Matthew Dawson, David M. Smith, Christine Fennema-Notestine, Michael J. Taylor, Rebecca Theilmann, Anthony C. Gamst, Clint Cushman, Ian Abramson, Florin Vaida, Jennifer Marquie-Beck, Vincent Rogalski, David Simpson, Letty Mintz, Will Toperoff, Ann Collier, Christina Marra, Trudy Jones, Benjamin Gelman, Eleanor Head, Muhammad Al-Lozi, Mengesha Teshome

School of Medicine

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Background. Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. Methods. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4+ T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. Results. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Conclusions. Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons.

Original language	English (US)
Pages (from-to)	1065-1073
Number of pages	9
Journal	Journal of Infectious Diseases
Volume	213
Issue number	7
DOIs	https://doi.org/10.1093/infdis/jiv754
State	Published - Apr 1 2016

Keywords

Anemia
HIV-associated neurocognitive disorder
Human immunodeficiency virus (HIV)
Iron metabolism
Mitochondrial dysfunction
Neurocognitive impairment
Red blood cell indices

ASJC Scopus subject areas

General Medicine

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10.1093/infdis/jiv754

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Kallianpur, A. R., Wang, Q., Jia, P., Hulgan, T., Zhao, Z., Letendre, S. L., Ellis, R. J., Heaton, R. K., Franklin, D. R., Barnholtz-Sloan, J., Collier, A. C., Marra, C. M., Clifford, D. B., Gelman, B. B., McArthur, J. C., Morgello, S., Simpson, D. M., McCutchan, J. A., Grant, I., ... Teshome, M. (2016). Anemia and red blood cell indices predict HIV-associated neurocognitive impairment in the highly active antiretroviral therapy era. Journal of Infectious Diseases, 213(7), 1065-1073. https://doi.org/10.1093/infdis/jiv754

Kallianpur, AR, Wang, Q, Jia, P, Hulgan, T, Zhao, Z, Letendre, SL, Ellis, RJ, Heaton, RK, Franklin, DR, Barnholtz-Sloan, J, Collier, AC, Marra, CM, Clifford, DB, Gelman, BB, McArthur, JC, Morgello, S, Simpson, DM, McCutchan, JA, Grant, I, McCutchan, JA, Marcotte, TD, Franklin, D, Alexander, T, Capparelli, E, Atkinson, JH, Woods, SP, Dawson, M, Smith, DM, Fennema-Notestine, C, Taylor, MJ, Theilmann, R, Gamst, AC, Cushman, C, Abramson, I, Vaida, F, Marquie-Beck, J, Rogalski, V, Simpson, D, Mintz, L, Toperoff, W, Collier, A, Marra, C, Jones, T, Gelman, B, Head, E, Al-Lozi, M & Teshome, M 2016, 'Anemia and red blood cell indices predict HIV-associated neurocognitive impairment in the highly active antiretroviral therapy era', Journal of Infectious Diseases, vol. 213, no. 7, pp. 1065-1073. https://doi.org/10.1093/infdis/jiv754

@article{3dacd78f9fe842f3bafa36b3b701e975,

title = "Anemia and red blood cell indices predict HIV-associated neurocognitive impairment in the highly active antiretroviral therapy era",

abstract = "Background. Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. Methods. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4+ T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. Results. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Conclusions. Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons.",

keywords = "Anemia, HIV-associated neurocognitive disorder, Human immunodeficiency virus (HIV), Iron metabolism, Mitochondrial dysfunction, Neurocognitive impairment, Red blood cell indices",

author = "Kallianpur, {Asha R.} and Quan Wang and Peilin Jia and Todd Hulgan and Zhongming Zhao and Letendre, {Scott L.} and Ellis, {Ronald J.} and Heaton, {Robert K.} and Franklin, {Donald R.} and Jill Barnholtz-Sloan and Collier, {Ann C.} and Marra, {Christina M.} and Clifford, {David B.} and Gelman, {Benjamin B.} and McArthur, {Justin C.} and Susan Morgello and Simpson, {David M.} and McCutchan, {J. A.} and Igor Grant and McCutchan, {J. Allen} and Marcotte, {Thomas D.} and Donald Franklin and Terry Alexander and Edmund Capparelli and Atkinson, {J. Hampton} and Woods, {Steven Paul} and Matthew Dawson and Smith, {David M.} and Christine Fennema-Notestine and Taylor, {Michael J.} and Rebecca Theilmann and Gamst, {Anthony C.} and Clint Cushman and Ian Abramson and Florin Vaida and Jennifer Marquie-Beck and Vincent Rogalski and David Simpson and Letty Mintz and Will Toperoff and Ann Collier and Christina Marra and Trudy Jones and Benjamin Gelman and Eleanor Head and Muhammad Al-Lozi and Mengesha Teshome",

note = "Funding Information: We gratefully acknowledge the contributions of all participants in the CHARTER study. The CHARTER study is supported by the National Institutes of Health (contracts N01 MH22005, R01 MH095621 to A. R. K. and T. H., and HHSN271201000036C to I. G.). Publisher Copyright: {\textcopyright} The Author 2015.",

year = "2016",

month = apr,

day = "1",

doi = "10.1093/infdis/jiv754",

language = "English (US)",

volume = "213",

pages = "1065--1073",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "7",

}

TY - JOUR

T1 - Anemia and red blood cell indices predict HIV-associated neurocognitive impairment in the highly active antiretroviral therapy era

AU - Kallianpur, Asha R.

AU - Wang, Quan

AU - Jia, Peilin

AU - Hulgan, Todd

AU - Zhao, Zhongming

AU - Letendre, Scott L.

AU - Ellis, Ronald J.

AU - Heaton, Robert K.

AU - Franklin, Donald R.

AU - Barnholtz-Sloan, Jill

AU - Collier, Ann C.

AU - Marra, Christina M.

AU - Clifford, David B.

AU - Gelman, Benjamin B.

AU - McArthur, Justin C.

AU - Morgello, Susan

AU - Simpson, David M.

AU - McCutchan, J. A.

AU - Grant, Igor

AU - McCutchan, J. Allen

AU - Marcotte, Thomas D.

AU - Franklin, Donald

AU - Alexander, Terry

AU - Capparelli, Edmund

AU - Atkinson, J. Hampton

AU - Woods, Steven Paul

AU - Dawson, Matthew

AU - Smith, David M.

AU - Fennema-Notestine, Christine

AU - Taylor, Michael J.

AU - Theilmann, Rebecca

AU - Gamst, Anthony C.

AU - Cushman, Clint

AU - Abramson, Ian

AU - Vaida, Florin

AU - Marquie-Beck, Jennifer

AU - Rogalski, Vincent

AU - Simpson, David

AU - Mintz, Letty

AU - Toperoff, Will

AU - Collier, Ann

AU - Marra, Christina

AU - Jones, Trudy

AU - Gelman, Benjamin

AU - Head, Eleanor

AU - Al-Lozi, Muhammad

AU - Teshome, Mengesha

N1 - Funding Information: We gratefully acknowledge the contributions of all participants in the CHARTER study. The CHARTER study is supported by the National Institutes of Health (contracts N01 MH22005, R01 MH095621 to A. R. K. and T. H., and HHSN271201000036C to I. G.). Publisher Copyright: © The Author 2015.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background. Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. Methods. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4+ T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. Results. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Conclusions. Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons.

AB - Background. Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. Methods. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4+ T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. Results. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Conclusions. Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons.

KW - Anemia

KW - HIV-associated neurocognitive disorder

KW - Human immunodeficiency virus (HIV)

KW - Iron metabolism

KW - Mitochondrial dysfunction

KW - Neurocognitive impairment

KW - Red blood cell indices

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UR - http://www.scopus.com/inward/citedby.url?scp=84962528745&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiv754

DO - 10.1093/infdis/jiv754

M3 - Article

C2 - 26690344

AN - SCOPUS:84962528745

SN - 0022-1899

VL - 213

SP - 1065

EP - 1073

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 7

ER -

Anemia and red blood cell indices predict HIV-associated neurocognitive impairment in the highly active antiretroviral therapy era

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