HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study
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OBJECTIVES: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). METHODS: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). RESULTS: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm(3) (30% vs 47% in remaining subgroups). CONCLUSIONS: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.
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Physical activity may be an important measure for reducing HAND.
“Physical activity may be an important measure for reducing HAND.[8]”
From Management of psychiatric disorders with HIV and dermatological disorders (2022) · cites this paper as [8]
The Discussion addresses antiretroviral therapy and possible approaches to preventing or treating HAND, but does not address physical activity. Searches for “physical activity,” “exercise,” and lifestyle interventions found no passage linking them to reduced HAND. Page numbers were not available in our copy. (LLM, conf=0.76)
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- ington, Seattle Site: Ann Collier, MD (Co-P.I.), and Christina Marra, MD (Co-P.I.), Trudy Jones, MN, ARNP; University of Texas, Galveston Site: Benjamin Gelman, MD, PhD (P.I.), Eleanor Head, RN, BSN; and Washington University, St. Louis Site: David Clifford, MD (P.I.), Mu- hammad Al-Lozi, MD, Mengesha Teshome, MD. DISCLOSURE Dr. Heaton serves on a scientific advisory board for the NINCDS; serves on the editorial boards of the Journal of the International Neuropsychologi- cal Society, the Journal of Clinical and Experimental Neuropsychology, and The Clinical Neuropsychologist; has received royalties from the publication of Revised Comprehensive Norms for and Expanded Halstead-Reitan Battery: Demographically Adjusted Neuropsychological Norms for African American and Caucasian Adults (Psychological Assessment Resources, Inc., 1991- present), Revised Comprehensive Norms for and Expanded Halstead-Reitan Battery: Demographically Adjusted Neuropsychological Norms for African American and Caucasian Adults Scoring Program (Psychological Assess- ment Resources, Inc., 1994-present), and Wisconsin Card Sorting Test Manual-Revised and Expanded (Psychological Assessment Resources, Inc., 1991-present); and receives research support from the NIH (P30 MH62512 [coinvestigator], P50 DA26306 [coinvestigator], P01 DA12065 [coinvestigator], R01 MH60720 [coinvestigator], R01 MH73433
- Mr. Franklin receives research support from the NIH (NIMH N01 MH22005 [Center Manager]). Dr. Woods serves as Book Review Editor for the Journal of Clinical and Experimental Neuropsychology and on the editorial board of Archives of Clinical Neuropsychology; and receives re- search support from the NIH (P30 MH62512 [coinvestigator], P50 DA26306 [coinvestigator], N01 MH22005 [coinvestigator], R01 MH73419
- Henry M. Jackson Foundation. Dr. Ake has received research support from the NIH (NIHM N01 MH22005 [statistician] and NIHM P30 MH62512 [statistician]). Dr. Vaida served on a scientific advisory board for Ardea Biosciences, Inc.; serves as Research Methodol- ogy Section Editor for the Californian Journal of Health Promotion; and receives research support from Precision Photonics Corporation and the NIH (P30 MH62512 [coinvestigator], P50 DA26306 [coinvestigator], N01 MH22005 [coinvestigator], R01 MH083552 [coinvestigator], NIH R01 AI47033 [subcontract PI], U01 AI74521 [coinvestigator], R01 MH085608
- and AI068543 [coinvestigator]. Dr. Ellis serves on the editorial advisory board for the Journal of Neuroimmune Pharmacology; has served on the speakers' bureau for and received speaker honoraria from GlaxoSmithKline; and has received research support from the NIH (R01 MH058076-12 [PI], P30 MH062512-09 [coinvestigator], DA012065-10 [coinvestigator], N01 MH22005-08 [coinvestigator], MH083506-02 [coinvestigator], MH083552-02 [coinvestigator], DA026306-01 [coinvestigator], MH085608-01 [coinvestigator], and DA026146 [coinvestigator]). Dr. Letendre serves on a scientific advisory board for Tibotec Therapeutics; has received speaker honoraria from Gl- axoSmithKline, Tibotec Therapeutics, and Abbott; and receives research support from Abbott, Merck Serono, Tibotec Therapeutics, Schering- Plough Corp., GlaxoSmithKline, and the NIH (N01 MH22005 [co- investigator], R01 MH58076 [coinvestigator], P01 DA12065
- Dr. Collier serves/has served on scientific advisory boards for Merck & Co., Inc.; Pfizer Inc, and GlaxoSmithKline; receives/has re- ceived research support from Merck & Co., Inc., Schering-Plough Corp, Boehringer Ingelheim, Gilead Sciences, Inc., Koronis Pharmaceuticals, Johnson & Johnson, and the NIH (NIAID AI 069434 [PI], NIAID AI27757 [PI on Core], NIHM N01 MH22005 [Site PI], NIAID AI069918 [coinvestigator of subcontract], NINDS RC1NS068904 [co- investigator], NIAID P01 AI 057005 [PI on Core], and NIAID AI069438 [PI of Subcontract]); and she and an immediate family mem- ber own stock in Abbott and Bristol-Myers Squibb. Dr. Marra receives royalties from the publication of Infections of the Central Nervous System, 3d edition (Lippincott Williams & Wilkins, 2004) and from an article in UptoDate; and receives research support from the NIH (1R01 NS/AI 34235 [PI], N01 MH22005 [coinvestigator]). Dr. Gelman receives re- search support from the NIH/NIMH (U01MH083507 [PI], R01MH079886 [PI], and N01MH022005 [PI]). Dr. McArthur serves as a consultant to Allergan, Inc., Pfizer Inc, and Biogen Idec; receives royal- ties from the publication of Current Therapy in Neurologic Disease, 7th edition (Mosby, 2006); is an author on patents re: Device for thermal stimulation of small neural fibers and Immunophilin ligand treatment of antiretroviral toxic neuropathy; and receives research support from Biogen Idec, the NIH (R01 MH075673 [PI], RO1 NS44807 [PI], RO1 NS49465 [PI], and R01 MH067831 [Co-I]), the National Multiple Scle- rosis Society, and the Foundation for Peripheral Neuropathy. Dr. Morg- ello has received research support from the NIH (U01MH083501 [PI] and N01MH22005 [PI]). Dr. Simpson has served on scientific advisory boards for Pfizer Inc, Cephalon, Inc., Eli Lilly and Company, Glaxo- SmithKline, Allergan, Inc., Merz Pharmaceuticals LLC, MEDA Pharma- ceuticals Ltd., Boehringer Ingelheim, Endo Pharmaceuticals, Biogen Idec, and Alpharma Inc.; serves on the editorial board of AIDS Patient Care; has served on speakers' bureaus for and received speaker honoraria from Eli Lilly and Company and GlaxoSmithKline; has served as a consultant for NeurogesX, Eli Lilly and Company, Regeneron Pharmaceuticals, Inc., GlaxoSmithKline, Allergan, Inc., Merz Pharmaceuticals LLC, and Torrey Pines; and receives research support from NeurogesX, Pfizer Inc, Allergan, Inc., Eli Lilly and Company, and the NIH (NINDS R01-NS-328-05
- Dr. Abramson serves as an Associate Editor for the Journal of Nonparamet- ric Statistics; and receives research support from the NIH (P30 MH62512 [coinvestigator], P50 DA26306 [coinvestigator], R01 MH61146 [coin- vestigator], N01 MH22005 [coinvestigator], R01 DA21115 [coinvestiga- tor], and R21 MH78728 [coinvestigator]). Dr. Gamst receives research 2094 Neurology 75 December 7, 2010 support from Pfizer Inc, and the NIH (P30 MH62512 [coinvestigator], P50 DA26306 [coinvestigator], R01 HL95089 [coinvestigator], U01 MH83506 [coinvestigator], R01 HL84229 [coinvestigator], R01 MH79752
- and from the Lundbeck Foundation. Dr. Wong has served on a scientific advisory board for Abbott; serves on the editorial boards of the Journal of AIDS and AIDS Research and Therapy; has re- ceived research material support from Bristol-Myers Squibb; and has re- ceived research support from the NIH (R01 NS051132 [PI] and N01 MH22005 [Core PI], R21 MH083573 [PI], and R01 AI087145 [coin- vestigator], and from the US Department of Veterans Affairs. Dr. Grant serves as an Associate Editor for the Journal of Neurovirology; and receives research support from the NIH (NIMH P30 MH62512 [PI], NIDA P50 DA26306 [PI], NIDA P01 DA12065 [PI], NIMH N01 MH22005 [PI], NIMH U01 MH83506 [PI], NIMH R01 MH78748 [coinvestigator], NIA R01 AG15301 [PI], NIMH R01 MH83552 [coinvestigator], and NIH/University of Nebraska P01 DA026146 [subcontract PI]).
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- Authors
- Heaton, R. K., Clifford, D. B., Franklin, D. R., Woods, S. P., Ake, C., Vaida, F., Ellis, R. J., Letendre, S. L., Marcotte, T. D., Atkinson, J. H., Rivera-Mindt, M., Vigil, O. R., Taylor, M. J., Collier, A. C., Marra, C. M., Gelman, B. B., McArthur, J. C., Morgello, S., Simpson, D. M., McCutchan, J. A., Abramson, I., Gamst, A., Fennema-Notestine, C., Jernigan, T. L., Wong, J., Grant, I., & For the CHARTER Group
- Affiliations
- University of California San Diego (US)
- From the University of California (R.K.H., D.R.F., S.P.W., C.A., F.V., R.J.E., S.L.L., T.D.M., J.H.A., O.R.V., M.J.T., J.A.M., I.A., A.G., C.F.-N., T.L.J., I.G.), San Diego; University of California (J.W.), San Francisco; Washington University (D.B.C.), St. Louis, MO; Mount Sinai School of Medicine (M.R.-M., S.M., D.M.S.), New York, NY; University of Washington (A.C.C., C.M.M.), Seattle; University of Texas Medical Branch (B.B.G.), Galveston; and Johns Hopkins University (J.C.M.), Baltimore, MD.
- ORCID
- Venue
- Neurology
- Published
- 2010-12-07
- Volume
- 75
- Issue
- 23
- Pages
- 2087-2096
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2995535
- OpenAlex
- W2137321682
- Cited by
- 2,353
- References
- 33
- Citations by year
- 2026: 92 · 2025: 93 · 2024: 119 · 2023: 131 · 2022: 127 · 2021: 182 · 2020: 172 · 2019: 225 · 2018: 153 · 2017: 202 · 2016: 181 · 2015: 172 · 2014: 165 · 2013: 152 · 2012: 115
- FWCI
- 38.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Fordham Research Commons (Fordham University) (submittedVersion)
- Funders
- National Institutes of Health (5u01ai069495-05, n01mh22005-16-0-1, 5r01ag024506-03, 5r01ns036524-10, N01 MH22005, MH22005)
- Centers for Disease Control and Prevention (U2G PS00623)
- U.S. Public Health Service (R213857-53187, NIMH-22005)
- National Institute on Alcohol Abuse and Alcoholism (R01 AA13419, R01AA013419, R32AA17321)
- National Institute on Aging (R01AG015301, U01‐AG10483, R01AG031224, R01-AG024506, R01 AG-15301, U01AG010483, R01AG022381, U19AG010483)
- National Heart, Lung, and Blood Institute (R01HL084229, R01 HL95089, R01 HL84229, R01HL095089)
- National Institute of Mental Health (U01MH083507, U01-MH83506, R21-MH85610, R01MH067831, U01MH083506, R01-MH73419, N01 MH-22005, R01 MH73433, R01MH079881, N01 MH22005-08, R01 MH-60720, R01 MH78748, R01MH058076, R21MH78728, MH 22005, N01MH022005, R01MH064907, K23MH079718, R01MH081861, MH058076, R01MH085608, R01 MH78737, R01MH64907, R01MH083552, R01MH073419, R24-MH-59724, U13 MH81676, R32 MH77487, R01MH079886, R24MH059724, R21MH078728, U01MH083501, R01MH38552, R01MH078737, R21MH085610, R01 MH81861, R01 MH83552, R01 MH79752, R01MH078748, R01MH073433, R01MH079752, R01MH060720, P30MH62512, R01MH061146, MH085608-01, MH083506-02, R01 MH61146, R01 MH79881, R01 MH075673, R21MH083573, R01MH084796, MH083552-02, P30MH062512, U13MH081676, R01 MH58076)
- National Institute on Drug Abuse (P50DA026306, R01 DA21115, RC2DA029475, DA026306-01, P01DA012065, P50DA26306, RC2-DA29475, P01-DA12065, DA012065-10, DA026146, P01DA026146, R03DA022137, R01DA021115)
- National Institute of Allergy and Infectious Diseases (AI 27757, R01-AI47033, AI-069434, AI069918, UO1AI69495, U01 AI74521, U01AI074521, R01AI034235, U01AI069432, R01AI047033, 00-AI-0005, U01 AI69432, R01AI087145, P01AI057005, AI069438, AI068543, 1R01 NS/AI34235, P30AI027757, U01AI069918)
- National Institute of Neurological Disorders and Stroke (R01 NS44807, R21NS069355, R01NS049465, UO1 NS32228, R01NS044807, R01NS49465, RC1NS068904, R01-NS-41198, R01NS041198, R01-NS36524, R01NS051132, U01NS032228)
- National Center for Research Resources (U24RR021992, U24RR021382, K30RR22681, K30RR022681, U24 RR21382, U24RR019701)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
- Keywords
- HIV-associated neurocognitive disorders, HIV-associated dementia, highly active antiretroviral therapy, CD4 nadir, viral suppression, comorbidities, asymptomatic neurocognitive impairment, mild neurocognitive disorder, HIV infection
- MeSH terms
- Activities of Daily Living, Adult, Algorithms, Cognition Disorders, Disability Evaluation, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Neurologic Examination, Neuropsychological Tests, Psychiatric Status Rating Scales, Retrospective Studies, Models, Statistical, HIV Infections, Cross-Over Studies, Observation, Antiretroviral Therapy, Highly Active
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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