Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline

Igor Grant, Donald R. Franklin, Reena Deutsch, Steven P. Woods, Florin Vaida, Ronald J. Ellis, Scott L. Letendre, Thomas D. Marcotte, J. H. Atkinson, Ann C. Collier, Christina M. Marra, David B. Clifford, Benjamin Gelman, Justin C. McArthur, Susan Morgello, David M. Simpson, John A. McCutchan, Ian Abramson, Anthony Gamst, Christine Fennema-Notestine & 2 others Davey M. Smith, Robert K. Heaton

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Objective: While HIV-associated neurocognitive disorders (HAND) remain prevalent despite combination antiretroviral therapy (CART), the clinical relevance of asymptomatic neurocognitive impairment (ANI), the most common HAND diagnosis, remains unclear. We investigated whether HIV-infected persons with ANI were more likely than those who were neurocognitively normal (NCN) to experience a decline in everyday functioning (symptomatic decline). Methods: A total of 347 human participants from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort were NCN (n = 226) or had ANI (n = 121) at baseline. Neurocognitive assessments occurred approximately every 6 months, with median (interquartile range) follow-up of 45.2 (28.7-63.7) months. Symptomatic decline was based on self-report (SR) or objective, performance-based (PB) problems in everyday functioning. Proportional hazards modeling was used to generate risk ratios for progression to symptomatic HAND after adjusting for baseline and time-dependent covariates, including CD41 T-lymphocyte count (CD4), virologic suppression, CART, and mood. Results: The ANI group had a shorter time to symptomatic HAND than the NCN after adjusting for baseline predictors: adjusted risk ratios for symptomatic HAND were 2.0 (confidence interval [CI] 1.1-3.6; p = 0.02) for SR, 5.8 (CI 3.2-10.7; p < 0.0001) for PB, and 3.2 (CI 2.0-5.0; p < 0.0001) for either SR or PB. Current CD4 and depression were significant time-dependent covariates, but antiretroviral regimen, virologic suppression, and substance abuse or dependence were not. Conclusions: This longitudinal study demonstrates that ANI conveys a 2-fold to 6-fold increase in risk for earlier development of symptomatic HAND, supporting the prognostic value of the ANI diagnosis in clinical settings. Identifying those at highest risk for symptomatic decline may offer an opportunity to modify treatment to delay progression.

Original languageEnglish (US)
Pages (from-to)2055-2062
Number of pages8
JournalNeurology
Volume82
Issue number23
DOIs
StatePublished - Jun 10 2014

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HIV
Self Report
Confidence Intervals
Substance-Related Disorders
Odds Ratio
Cohort Effect
Impairment
AIDS/HIV
Lymphocyte Count
Longitudinal Studies
Neurocognitive Disorders
Therapeutics
Depression
T-Lymphocytes
Research
Antiretroviral Therapy
Confidence Interval
Self-report
Suppression
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ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Grant, I., Franklin, D. R., Deutsch, R., Woods, S. P., Vaida, F., Ellis, R. J., ... Heaton, R. K. (2014). Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology, 82(23), 2055-2062. https://doi.org/10.1212/WNL.0000000000000492

Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. / Grant, Igor; Franklin, Donald R.; Deutsch, Reena; Woods, Steven P.; Vaida, Florin; Ellis, Ronald J.; Letendre, Scott L.; Marcotte, Thomas D.; Atkinson, J. H.; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin; McArthur, Justin C.; Morgello, Susan; Simpson, David M.; McCutchan, John A.; Abramson, Ian; Gamst, Anthony; Fennema-Notestine, Christine; Smith, Davey M.; Heaton, Robert K.

In: Neurology, Vol. 82, No. 23, 10.06.2014, p. 2055-2062.

Research output: Contribution to journalArticle

Grant, I, Franklin, DR, Deutsch, R, Woods, SP, Vaida, F, Ellis, RJ, Letendre, SL, Marcotte, TD, Atkinson, JH, Collier, AC, Marra, CM, Clifford, DB, Gelman, B, McArthur, JC, Morgello, S, Simpson, DM, McCutchan, JA, Abramson, I, Gamst, A, Fennema-Notestine, C, Smith, DM & Heaton, RK 2014, 'Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline', Neurology, vol. 82, no. 23, pp. 2055-2062. https://doi.org/10.1212/WNL.0000000000000492
Grant I, Franklin DR, Deutsch R, Woods SP, Vaida F, Ellis RJ et al. Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology. 2014 Jun 10;82(23):2055-2062. https://doi.org/10.1212/WNL.0000000000000492
Grant, Igor ; Franklin, Donald R. ; Deutsch, Reena ; Woods, Steven P. ; Vaida, Florin ; Ellis, Ronald J. ; Letendre, Scott L. ; Marcotte, Thomas D. ; Atkinson, J. H. ; Collier, Ann C. ; Marra, Christina M. ; Clifford, David B. ; Gelman, Benjamin ; McArthur, Justin C. ; Morgello, Susan ; Simpson, David M. ; McCutchan, John A. ; Abramson, Ian ; Gamst, Anthony ; Fennema-Notestine, Christine ; Smith, Davey M. ; Heaton, Robert K. / Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. In: Neurology. 2014 ; Vol. 82, No. 23. pp. 2055-2062.
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abstract = "Objective: While HIV-associated neurocognitive disorders (HAND) remain prevalent despite combination antiretroviral therapy (CART), the clinical relevance of asymptomatic neurocognitive impairment (ANI), the most common HAND diagnosis, remains unclear. We investigated whether HIV-infected persons with ANI were more likely than those who were neurocognitively normal (NCN) to experience a decline in everyday functioning (symptomatic decline). Methods: A total of 347 human participants from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort were NCN (n = 226) or had ANI (n = 121) at baseline. Neurocognitive assessments occurred approximately every 6 months, with median (interquartile range) follow-up of 45.2 (28.7-63.7) months. Symptomatic decline was based on self-report (SR) or objective, performance-based (PB) problems in everyday functioning. Proportional hazards modeling was used to generate risk ratios for progression to symptomatic HAND after adjusting for baseline and time-dependent covariates, including CD41 T-lymphocyte count (CD4), virologic suppression, CART, and mood. Results: The ANI group had a shorter time to symptomatic HAND than the NCN after adjusting for baseline predictors: adjusted risk ratios for symptomatic HAND were 2.0 (confidence interval [CI] 1.1-3.6; p = 0.02) for SR, 5.8 (CI 3.2-10.7; p < 0.0001) for PB, and 3.2 (CI 2.0-5.0; p < 0.0001) for either SR or PB. Current CD4 and depression were significant time-dependent covariates, but antiretroviral regimen, virologic suppression, and substance abuse or dependence were not. Conclusions: This longitudinal study demonstrates that ANI conveys a 2-fold to 6-fold increase in risk for earlier development of symptomatic HAND, supporting the prognostic value of the ANI diagnosis in clinical settings. Identifying those at highest risk for symptomatic decline may offer an opportunity to modify treatment to delay progression.",
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AU - Grant, Igor

AU - Franklin, Donald R.

AU - Deutsch, Reena

AU - Woods, Steven P.

AU - Vaida, Florin

AU - Ellis, Ronald J.

AU - Letendre, Scott L.

AU - Marcotte, Thomas D.

AU - Atkinson, J. H.

AU - Collier, Ann C.

AU - Marra, Christina M.

AU - Clifford, David B.

AU - Gelman, Benjamin

AU - McArthur, Justin C.

AU - Morgello, Susan

AU - Simpson, David M.

AU - McCutchan, John A.

AU - Abramson, Ian

AU - Gamst, Anthony

AU - Fennema-Notestine, Christine

AU - Smith, Davey M.

AU - Heaton, Robert K.

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N2 - Objective: While HIV-associated neurocognitive disorders (HAND) remain prevalent despite combination antiretroviral therapy (CART), the clinical relevance of asymptomatic neurocognitive impairment (ANI), the most common HAND diagnosis, remains unclear. We investigated whether HIV-infected persons with ANI were more likely than those who were neurocognitively normal (NCN) to experience a decline in everyday functioning (symptomatic decline). Methods: A total of 347 human participants from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort were NCN (n = 226) or had ANI (n = 121) at baseline. Neurocognitive assessments occurred approximately every 6 months, with median (interquartile range) follow-up of 45.2 (28.7-63.7) months. Symptomatic decline was based on self-report (SR) or objective, performance-based (PB) problems in everyday functioning. Proportional hazards modeling was used to generate risk ratios for progression to symptomatic HAND after adjusting for baseline and time-dependent covariates, including CD41 T-lymphocyte count (CD4), virologic suppression, CART, and mood. Results: The ANI group had a shorter time to symptomatic HAND than the NCN after adjusting for baseline predictors: adjusted risk ratios for symptomatic HAND were 2.0 (confidence interval [CI] 1.1-3.6; p = 0.02) for SR, 5.8 (CI 3.2-10.7; p < 0.0001) for PB, and 3.2 (CI 2.0-5.0; p < 0.0001) for either SR or PB. Current CD4 and depression were significant time-dependent covariates, but antiretroviral regimen, virologic suppression, and substance abuse or dependence were not. Conclusions: This longitudinal study demonstrates that ANI conveys a 2-fold to 6-fold increase in risk for earlier development of symptomatic HAND, supporting the prognostic value of the ANI diagnosis in clinical settings. Identifying those at highest risk for symptomatic decline may offer an opportunity to modify treatment to delay progression.

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