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Cited by 2,353HIV Research and TreatmentHIV/AIDS drug development and treatmentInfectious Diseases and Tuberculosis

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HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study

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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·2010·Neurology
DOI 10.1212/wnl.0b013e318200d727PMC PMC2995535
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Abstract

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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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
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2010-12-07
Volume
75
Issue
23
Pages
2087-2096
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0b013e318200d727
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
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 › Infectious Diseases › 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

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