Neurocognitive change in the era of HIV combination antiretroviral therapy: The longitudinal CHARTER study

Robert K. Heaton, Donald R. Franklin, Reena Deutsch, Scott Letendre, Ronald J. Ellis, Kaitlin Casaletto, Maria J. Marquine, Steven P. Woods, Florin Vaida, J. Hampton Atkinson, Thomas D. Marcotte, J. Allen McCutchan, Ann C. Collier, Christina M. Marra, David B. Clifford, Benjamin Gelman, Ned Sacktor, Susan Morgello, David M. Simpson, Ian AbramsonAnthony C. Gamst, Christine Fennema-Notestine, David M. Smith, Igor Grant

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P <. 0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.

Original languageEnglish (US)
Pages (from-to)473-480
Number of pages8
JournalClinical Infectious Diseases
Volume60
Issue number3
DOIs
StatePublished - Feb 1 2015
Externally publishedYes

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Longitudinal Studies
HIV
Virus Diseases
Therapeutics
Cohort Effect
Survival Analysis
Aspartate Aminotransferases
Intelligence
Hematocrit
Mental Disorders
Comorbidity
Albumins
Demography
Clinical Trials
Depression
Viruses
Incidence
Research
Proteins
Neurocognitive Disorders

Keywords

  • antiretroviral therapy
  • cognitive change
  • comorbidities
  • HIV

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

Heaton, R. K., Franklin, D. R., Deutsch, R., Letendre, S., Ellis, R. J., Casaletto, K., ... Grant, I. (2015). Neurocognitive change in the era of HIV combination antiretroviral therapy: The longitudinal CHARTER study. Clinical Infectious Diseases, 60(3), 473-480. https://doi.org/10.1093/cid/ciu862

Neurocognitive change in the era of HIV combination antiretroviral therapy : The longitudinal CHARTER study. / Heaton, Robert K.; Franklin, Donald R.; Deutsch, Reena; Letendre, Scott; Ellis, Ronald J.; Casaletto, Kaitlin; Marquine, Maria J.; Woods, Steven P.; Vaida, Florin; Atkinson, J. Hampton; Marcotte, Thomas D.; McCutchan, J. Allen; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin; Sacktor, Ned; Morgello, Susan; Simpson, David M.; Abramson, Ian; Gamst, Anthony C.; Fennema-Notestine, Christine; Smith, David M.; Grant, Igor.

In: Clinical Infectious Diseases, Vol. 60, No. 3, 01.02.2015, p. 473-480.

Research output: Contribution to journalArticle

Heaton, RK, Franklin, DR, Deutsch, R, Letendre, S, Ellis, RJ, Casaletto, K, Marquine, MJ, Woods, SP, Vaida, F, Atkinson, JH, Marcotte, TD, McCutchan, JA, Collier, AC, Marra, CM, Clifford, DB, Gelman, B, Sacktor, N, Morgello, S, Simpson, DM, Abramson, I, Gamst, AC, Fennema-Notestine, C, Smith, DM & Grant, I 2015, 'Neurocognitive change in the era of HIV combination antiretroviral therapy: The longitudinal CHARTER study', Clinical Infectious Diseases, vol. 60, no. 3, pp. 473-480. https://doi.org/10.1093/cid/ciu862
Heaton, Robert K. ; Franklin, Donald R. ; Deutsch, Reena ; Letendre, Scott ; Ellis, Ronald J. ; Casaletto, Kaitlin ; Marquine, Maria J. ; Woods, Steven P. ; Vaida, Florin ; Atkinson, J. Hampton ; Marcotte, Thomas D. ; McCutchan, J. Allen ; Collier, Ann C. ; Marra, Christina M. ; Clifford, David B. ; Gelman, Benjamin ; Sacktor, Ned ; Morgello, Susan ; Simpson, David M. ; Abramson, Ian ; Gamst, Anthony C. ; Fennema-Notestine, Christine ; Smith, David M. ; Grant, Igor. / Neurocognitive change in the era of HIV combination antiretroviral therapy : The longitudinal CHARTER study. In: Clinical Infectious Diseases. 2015 ; Vol. 60, No. 3. pp. 473-480.
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abstract = "Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7{\%}) declined, 265 (60.8{\%}) remained stable, and 72 (16.5{\%}) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P <. 0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.",
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T1 - Neurocognitive change in the era of HIV combination antiretroviral therapy

T2 - The longitudinal CHARTER study

AU - Heaton, Robert K.

AU - Franklin, Donald R.

AU - Deutsch, Reena

AU - Letendre, Scott

AU - Ellis, Ronald J.

AU - Casaletto, Kaitlin

AU - Marquine, Maria J.

AU - Woods, Steven P.

AU - Vaida, Florin

AU - Atkinson, J. Hampton

AU - Marcotte, Thomas D.

AU - McCutchan, J. Allen

AU - Collier, Ann C.

AU - Marra, Christina M.

AU - Clifford, David B.

AU - Gelman, Benjamin

AU - Sacktor, Ned

AU - Morgello, Susan

AU - Simpson, David M.

AU - Abramson, Ian

AU - Gamst, Anthony C.

AU - Fennema-Notestine, Christine

AU - Smith, David M.

AU - Grant, Igor

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N2 - Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P <. 0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.

AB - Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P <. 0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.

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KW - cognitive change

KW - comorbidities

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