• 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 B Gelman, Justin C McArthur, Susan Morgello, David M Simpson, John A McCutchan, Ian Abramson, Anthony Gamst, Christine Fennema-Notestine, Davey M Smith, Robert K Heaton, and CHARTER Group.
• 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.
• Neurology. 2014 Jun 10;82(23):2055-62.

ObjectiveWhile 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).MethodsA 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.ResultsThe 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.ConclusionsThis 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.© 2014 American Academy of Neurology.

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