Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years

BACKGROUND:Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differ...

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Veröffentlicht in:Journal of acquired immune deficiency syndromes (1999) 2017-11, Vol.76 (3), p.289-297
Hauptverfasser: Clifford, Katherine M, Samboju, Vishal, Cobigo, Yann, Milanini, Benedetta, Marx, Gabriel A, Hellmuth, Joanna M, Rosen, Howard J, Kramer, Joel H, Allen, Isabel E, Valcour, Victor G
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container_end_page 297
container_issue 3
container_start_page 289
container_title Journal of acquired immune deficiency syndromes (1999)
container_volume 76
creator Clifford, Katherine M
Samboju, Vishal
Cobigo, Yann
Milanini, Benedetta
Marx, Gabriel A
Hellmuth, Joanna M
Rosen, Howard J
Kramer, Joel H
Allen, Isabel E
Valcour, Victor G
description BACKGROUND:Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared with that of healthy aging participants. METHODS:We examined longitudinal structural brain magnetic resonance imaging atrophy rates using region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants older than 60 years (n = 38) compared with age-matched HIV-uninfected healthy and cognitively normal controls (n = 24). RESULTS:The mean age of participants was 63 years, the mean estimated duration of infection was 21 years, and the median duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status. CONCLUSIONS:Despite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.
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Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared with that of healthy aging participants. METHODS:We examined longitudinal structural brain magnetic resonance imaging atrophy rates using region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants older than 60 years (n = 38) compared with age-matched HIV-uninfected healthy and cognitively normal controls (n = 24). RESULTS:The mean age of participants was 63 years, the mean estimated duration of infection was 21 years, and the median duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status. CONCLUSIONS:Despite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.</description><identifier>ISSN: 1525-4135</identifier><identifier>EISSN: 1944-7884</identifier><identifier>DOI: 10.1097/QAI.0000000000001489</identifier><identifier>PMID: 28650401</identifier><language>eng</language><publisher>United States: Copyright Wolters Kluwer Health, Inc. All rights reserved</publisher><subject>Age ; Aged ; Aging ; AIDS Dementia Complex - pathology ; AIDS Dementia Complex - virology ; AIDS/HIV ; Antiretroviral Therapy, Highly Active ; Atrophy ; Atrophy - pathology ; Brain ; Brain - pathology ; Brain injury ; Brain stem ; Case-Control Studies ; CD4 antigen ; Cerebellum ; Cognition ; Cognitive ability ; Cortex ; Female ; Frontal lobe ; Globus pallidus ; Head injuries ; Health risks ; HIV ; HIV Infections - complications ; HIV Infections - drug therapy ; Human immunodeficiency virus ; Humans ; Image processing ; Magnetic Resonance Imaging ; Male ; Medical treatment ; Middle Aged ; Morphometry ; Neuroimaging ; Patients ; Ribonucleic acid ; Risk management ; RNA ; Sexually transmitted diseases ; STD ; Substantia grisea ; Sustained Virologic Response ; Traumatic brain injury ; Viremia</subject><ispartof>Journal of acquired immune deficiency syndromes (1999), 2017-11, Vol.76 (3), p.289-297</ispartof><rights>Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.</rights><rights>Copyright Lippincott Williams &amp; Wilkins Ovid Technologies Nov 1, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4309-1116307afc77738905a5d709807e4b6d06e7e4ecafbf342730d4f9aabdaf25b23</citedby><cites>FETCH-LOGICAL-c4309-1116307afc77738905a5d709807e4b6d06e7e4ecafbf342730d4f9aabdaf25b23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28650401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Clifford, Katherine M</creatorcontrib><creatorcontrib>Samboju, Vishal</creatorcontrib><creatorcontrib>Cobigo, Yann</creatorcontrib><creatorcontrib>Milanini, Benedetta</creatorcontrib><creatorcontrib>Marx, Gabriel A</creatorcontrib><creatorcontrib>Hellmuth, Joanna M</creatorcontrib><creatorcontrib>Rosen, Howard J</creatorcontrib><creatorcontrib>Kramer, Joel H</creatorcontrib><creatorcontrib>Allen, Isabel E</creatorcontrib><creatorcontrib>Valcour, Victor G</creatorcontrib><title>Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years</title><title>Journal of acquired immune deficiency syndromes (1999)</title><addtitle>J Acquir Immune Defic Syndr</addtitle><description>BACKGROUND:Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared with that of healthy aging participants. METHODS:We examined longitudinal structural brain magnetic resonance imaging atrophy rates using region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants older than 60 years (n = 38) compared with age-matched HIV-uninfected healthy and cognitively normal controls (n = 24). RESULTS:The mean age of participants was 63 years, the mean estimated duration of infection was 21 years, and the median duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status. CONCLUSIONS:Despite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.</description><subject>Age</subject><subject>Aged</subject><subject>Aging</subject><subject>AIDS Dementia Complex - pathology</subject><subject>AIDS Dementia Complex - virology</subject><subject>AIDS/HIV</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Atrophy</subject><subject>Atrophy - pathology</subject><subject>Brain</subject><subject>Brain - pathology</subject><subject>Brain injury</subject><subject>Brain stem</subject><subject>Case-Control Studies</subject><subject>CD4 antigen</subject><subject>Cerebellum</subject><subject>Cognition</subject><subject>Cognitive ability</subject><subject>Cortex</subject><subject>Female</subject><subject>Frontal lobe</subject><subject>Globus pallidus</subject><subject>Head injuries</subject><subject>Health risks</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - drug therapy</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Image processing</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Middle Aged</subject><subject>Morphometry</subject><subject>Neuroimaging</subject><subject>Patients</subject><subject>Ribonucleic acid</subject><subject>Risk management</subject><subject>RNA</subject><subject>Sexually transmitted diseases</subject><subject>STD</subject><subject>Substantia grisea</subject><subject>Sustained Virologic Response</subject><subject>Traumatic brain injury</subject><subject>Viremia</subject><issn>1525-4135</issn><issn>1944-7884</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtPwzAQhC0E4lH4BwhZ4sIlxY6d2D6W8milShRRkDhFTrKhgTQJtkPVf49LASEO7GX38M1oNYPQMSV9SpQ4vxuM--TXUC7VFtqnivNASMm3_R2FUcApi_bQgbUvnok5V7toL5RxRDih-yidmubZgLXlO-ALo8saD5xp2vkKX4JtSwd4CsaW1kHt8GNpdIXvu7b9lDQ19vxo_Iin2pUesPi2ysHg2VzXOCb4CbSxh2in0JWFo6_dQw_XV7PhKJjc3oyHg0mQcUZUQCmNGRG6yIQQTCoS6SgXREkigKdxTmLwB2S6SAvGQ8FIzguldZrrIozSkPXQ2ca3Nc1bB9Yli9JmUFW6hqazCVWUSUbiUHr09A_60nSm9t95SnClaBivDfmGykxjrYEiaU250GaVUJKsO0h8B8nfDrzs5Mu8SxeQ_4i-Q_eA3ADLpnI-3NeqW4JJ5qArN__f-wMF9JF-</recordid><startdate>20171101</startdate><enddate>20171101</enddate><creator>Clifford, Katherine M</creator><creator>Samboju, Vishal</creator><creator>Cobigo, Yann</creator><creator>Milanini, Benedetta</creator><creator>Marx, Gabriel A</creator><creator>Hellmuth, Joanna M</creator><creator>Rosen, Howard J</creator><creator>Kramer, Joel H</creator><creator>Allen, Isabel E</creator><creator>Valcour, Victor G</creator><general>Copyright Wolters Kluwer Health, Inc. All rights reserved</general><general>Lippincott Williams &amp; Wilkins Ovid Technologies</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T2</scope><scope>7T5</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20171101</creationdate><title>Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years</title><author>Clifford, Katherine M ; Samboju, Vishal ; Cobigo, Yann ; Milanini, Benedetta ; Marx, Gabriel A ; Hellmuth, Joanna M ; Rosen, Howard J ; Kramer, Joel H ; Allen, Isabel E ; Valcour, Victor G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4309-1116307afc77738905a5d709807e4b6d06e7e4ecafbf342730d4f9aabdaf25b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Age</topic><topic>Aged</topic><topic>Aging</topic><topic>AIDS Dementia Complex - pathology</topic><topic>AIDS Dementia Complex - virology</topic><topic>AIDS/HIV</topic><topic>Antiretroviral Therapy, Highly Active</topic><topic>Atrophy</topic><topic>Atrophy - pathology</topic><topic>Brain</topic><topic>Brain - pathology</topic><topic>Brain injury</topic><topic>Brain stem</topic><topic>Case-Control Studies</topic><topic>CD4 antigen</topic><topic>Cerebellum</topic><topic>Cognition</topic><topic>Cognitive ability</topic><topic>Cortex</topic><topic>Female</topic><topic>Frontal lobe</topic><topic>Globus pallidus</topic><topic>Head injuries</topic><topic>Health risks</topic><topic>HIV</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - drug therapy</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Image processing</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Medical treatment</topic><topic>Middle Aged</topic><topic>Morphometry</topic><topic>Neuroimaging</topic><topic>Patients</topic><topic>Ribonucleic acid</topic><topic>Risk management</topic><topic>RNA</topic><topic>Sexually transmitted diseases</topic><topic>STD</topic><topic>Substantia grisea</topic><topic>Sustained Virologic Response</topic><topic>Traumatic brain injury</topic><topic>Viremia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Clifford, Katherine M</creatorcontrib><creatorcontrib>Samboju, Vishal</creatorcontrib><creatorcontrib>Cobigo, Yann</creatorcontrib><creatorcontrib>Milanini, Benedetta</creatorcontrib><creatorcontrib>Marx, Gabriel A</creatorcontrib><creatorcontrib>Hellmuth, Joanna M</creatorcontrib><creatorcontrib>Rosen, Howard J</creatorcontrib><creatorcontrib>Kramer, Joel H</creatorcontrib><creatorcontrib>Allen, Isabel E</creatorcontrib><creatorcontrib>Valcour, Victor G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Clifford, Katherine M</au><au>Samboju, Vishal</au><au>Cobigo, Yann</au><au>Milanini, Benedetta</au><au>Marx, Gabriel A</au><au>Hellmuth, Joanna M</au><au>Rosen, Howard J</au><au>Kramer, Joel H</au><au>Allen, Isabel E</au><au>Valcour, Victor G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years</atitle><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle><addtitle>J Acquir Immune Defic Syndr</addtitle><date>2017-11-01</date><risdate>2017</risdate><volume>76</volume><issue>3</issue><spage>289</spage><epage>297</epage><pages>289-297</pages><issn>1525-4135</issn><eissn>1944-7884</eissn><abstract>BACKGROUND:Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. 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In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status. CONCLUSIONS:Despite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.</abstract><cop>United States</cop><pub>Copyright Wolters Kluwer Health, Inc. 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subjects Age
Aged
Aging
AIDS Dementia Complex - pathology
AIDS Dementia Complex - virology
AIDS/HIV
Antiretroviral Therapy, Highly Active
Atrophy
Atrophy - pathology
Brain
Brain - pathology
Brain injury
Brain stem
Case-Control Studies
CD4 antigen
Cerebellum
Cognition
Cognitive ability
Cortex
Female
Frontal lobe
Globus pallidus
Head injuries
Health risks
HIV
HIV Infections - complications
HIV Infections - drug therapy
Human immunodeficiency virus
Humans
Image processing
Magnetic Resonance Imaging
Male
Medical treatment
Middle Aged
Morphometry
Neuroimaging
Patients
Ribonucleic acid
Risk management
RNA
Sexually transmitted diseases
STD
Substantia grisea
Sustained Virologic Response
Traumatic brain injury
Viremia
title Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years
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