Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline.

TitleAsymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline.
Publication TypeJournal Article
Year of Publication2014
AuthorsGrant, I, Franklin, DR, Deutsch, R, Woods, SP, Vaida, F, Ellis, RJ, Letendre, SL, Marcotte, TD, Atkinson, JH, Collier, AC, Marra, CM, Clifford, DB, Gelman, BB, McArthur, JC, Morgello, S, Simpson, DM, McCutchan, JA, Abramson, I, Gamst, A, Fennema-Notestine, C, Smith, DM, Heaton, RK
Corporate AuthorsCHARTER Group
JournalNeurology
Volume82
Issue23
Pagination2055-62
Date Published2014 Jun 10
ISSN1526-632X
KeywordsActivities of Daily Living, AIDS Dementia Complex, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Disease Progression, HIV Infections, Humans, Odds Ratio, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prospective Studies, Risk, Time Factors, Viral Load
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 CD4+ 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.

DOI10.1212/WNL.0000000000000492
Alternate JournalNeurology
PubMed ID24814848
PubMed Central IDPMC4118496
Grant List1R01MH101017 / MH / NIMH NIH HHS / United States
2U01NS32228 / NS / NINDS NIH HHS / United States
AI057005 / AI / NIAID NIH HHS / United States
AI068543 / AI / NIAID NIH HHS / United States
AI100665 / AI / NIAID NIH HHS / United States
AI27757 / AI / NIAID NIH HHS / United States
AI36214 / AI / NIAID NIH HHS / United States
AI69495 / AI / NIAID NIH HHS / United States
DA022137 / DA / NIDA NIH HHS / United States
DA034978 / DA / NIDA NIH HHS / United States
DP1 DA034978 / DA / NIDA NIH HHS / United States
K24 AI100665 / AI / NIAID NIH HHS / United States
K30 RR22681 / RR / NCRR NIH HHS / United States
MH097520 / MH / NIMH NIH HHS / United States
MH62512 / MH / NIMH NIH HHS / United States
MH83552 / MH / NIMH NIH HHS / United States
N01 MH22005 / MH / NIMH NIH HHS / United States
NR012907 / NR / NINR NIH HHS / United States
NS077384 / NS / NINDS NIH HHS / United States
P01 DA026146 / DA / NIDA NIH HHS / United States
P01 DA12065 / DA / NIDA NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
P30 MH075673 / MH / NIMH NIH HHS / United States
P30 MH62512 / MH / NIMH NIH HHS / United States
P30MH62512 / MH / NIMH NIH HHS / United States
P50 DA026306 / DA / NIDA NIH HHS / United States
P50 DA26306 / DA / NIDA NIH HHS / United States
P50DA26306 / DA / NIDA NIH HHS / United States
R01 AG022381 / AG / NIA NIH HHS / United States
R01 AG031224 / AG / NIA NIH HHS / United States
R01 AI090783 / AI / NIAID NIH HHS / United States
R01 AI47033 / AI / NIAID NIH HHS / United States
R01 DA21115 / DA / NIDA NIH HHS / United States
R01 HL84229 / HL / NHLBI NIH HHS / United States
R01 HL95089 / HL / NHLBI NIH HHS / United States
R01 MH042984-18S1 / MH / NIMH NIH HHS / United States
R01 MH079752 / MH / NIMH NIH HHS / United States
R01 MH083552 / MH / NIMH NIH HHS / United States
R01 MH084794 / MH / NIMH NIH HHS / United States
R01 MH092225-02S1 / MH / NIMH NIH HHS / United States
R01 MH097520 / MH / NIMH NIH HHS / United States
R01 MH58076 / MH / NIMH NIH HHS / United States
R01 MH60720 / MH / NIMH NIH HHS / United States
R01 MH61146 / MH / NIMH NIH HHS / United States
R01 MH73419 / MH / NIMH NIH HHS / United States
R01 MH73433 / MH / NIMH NIH HHS / United States
R01 MH78737 / MH / NIMH NIH HHS / United States
R01 MH78748 / MH / NIMH NIH HHS / United States
R01 MH79752 / MH / NIMH NIH HHS / United States
R01 MH80150 / MH / NIMH NIH HHS / United States
R01 MH83552 / MH / NIMH NIH HHS / United States
R01 MH92225 / MH / NIMH NIH HHS / United States
R01MH058076 / MH / NIMH NIH HHS / United States
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R01MH095621 / MH / NIMH NIH HHS / United States
R01MH83552 / MH / NIMH NIH HHS / United States
R01NS072005 / NS / NINDS NIH HHS / United States
R01NS079166 / NS / NINDS NIH HHS / United States
R21MH78728 / MH / NIMH NIH HHS / United States
R21NS069355 / NS / NINDS NIH HHS / United States
T32DA031098 / DA / NIDA NIH HHS / United States
U01 AG10483 / AG / NIA NIH HHS / United States
U01 AI69432 / AI / NIAID NIH HHS / United States
U01 AI74521 / AI / NIAID NIH HHS / United States
U01 MH83506 / MH / NIMH NIH HHS / United States
U01MH83506 / MH / NIMH NIH HHS / United States
U13 MH81676 / MH / NIMH NIH HHS / United States
U24MH100930-01 / MH / NIMH NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States