title: Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline.
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.
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY. igrant@ucsd.edu.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Franklin
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Reena
authors.initials: R
authors.lastname: Deutsch
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Woods
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Marcotte
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: J H
authors.initials: JH
authors.lastname: Atkinson
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: John A
authors.initials: JA
authors.lastname: McCutchan
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Ian
authors.initials: I
authors.lastname: Abramson
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gamst
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
authors.affiliation: From the University of California (I.G., D.R.F., R.D., S.P.W., F.V., R.J.E., S.L.L., T.D.M., J.H.A., J.A.M., I.A., A.G., C.F.-N., D.M.S., R.K.H.), San Diego; the University of Washington (A.C.C., C.M.M.), Seattle; Washington University (D.B.C.), St. Louis, MO; University of Texas Medical Branch (B.B.G.), Galveston; Johns Hopkins University (J.C.M.), Baltimore, MD; and The Icahn School of Medicine at Mount Sinai (S.M., D.M.S.), New York, NY.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
mesh_terms: D015526:AIDS Dementia Complex / Q000503:physiopathology*; D000203:Activities of Daily Living; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D018450:Disease Progression; D015658:HIV Infections / Q000145:classification / Q000503:physiopathology*; D006801:Humans; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D013997:Time Factors; D019562:Viral Load