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From the Department of Psychiatry (L.A.C., M.C., S.P.W., R.K.H.), Division of Biostatistics and Bioinformatics, Department of Family and Preventive Medicine (F.V.), Department of Medicine (S.L., S.G., J.A.M.), and Department of Neurosciences (R.J.E.), University of California at San Diego; and Brain Sciences (L.A.C.), University of New South Wales, Sydney, Australia.
Address correspondence and reprint requests to Dr. Lucette Cysique, Department of Neurology, St. Vincent’s Hospital, Xavier Building, Level 4, 390 Victoria Street, Darlinghurst, NSW 2010, Australia lcysique{at}unsw.edu.au
Objective: To rigorously evaluate the time course of cognitive change in a cohort of individuals with HIV-associated neurocognitive disorders (HAND) initiating combination antiretroviral therapy (CART), and to investigate which demographic, laboratory, and treatment factors are associated with neuropsychological (NP) outcome (or "any NP improvement").
Methods: Study participants included 37 HIV+ individuals with mild to moderate NP impairment who initiated CART and underwent NP testing at 12, 24, 36, and 48 weeks thereafter. NP change was assessed using a regression-based change score that was normed on a separate NP-stable group thereby controlling for regression toward the mean and practice effect. Mixed-effect regression models adjusting for loss to follow-up were used to evaluate the time course of cognitive change and its association with baseline and time-varying predictors.
Results: In persons with HAND initiating CART, cognitive improvement happens soon after initiation (13% at week 12), but more often 24, 36, and up to 48 weeks after initiation (up to 41%), with fewer than 5% demonstrating significant worsening. In multivariate analyses, unique predictors of NP improvement included more severe baseline NP impairment and higher CART CNS penetration index. Greater viral load decrease was associated with NP improvement only in univariate analyses.
Conclusion: Clinically meaningful neuropsychological improvement seemed to peak around 24–36 weeks after combination antiretroviral therapy initiation and was prolonged over the 1-year study period. This study also provides new evidence that benefit may be maximized by choosing antiretroviral medications that reach therapeutic concentrations in the CNS.
Abbreviations: ANI = asymptomatic neurocognitive impairment; CART = combination antiretroviral therapy; CI = confidence interval; CIT = Cognitive Intervention Trial; CPE = CNS penetration effectiveness; GDS = Global Deficit Score; IQR = interquartile range; HAD = HIV-associated dementia; HAND = HIV-associated neurocognitive disorders; MND = mild neurocognitive disorder; MS-Reg-CS = mean scaled score regression-based change score; NP = neuropsychological.
Supplemental data at www.neurology.org
Editorial, page 338
e-Pub ahead of print on May 27, 2009, at www.neurology.org.
Supported by NIH R01 MH50876 (PI, R. Ellis). Dr. Cysique received a post-doctoral fellowship from the HIV Neurobehavioral Research Center (HNRC). The HIV Neurobehavioral Research Center (HNRC) is supported by Center award MH 62512 from NIMH.
Disclosure: Author disclosures are provided at the end of the article.
The views expressed in this article are those of the authors and do not reflect the official policy or position of the US Department of the Navy, Department of Defense, or the United States Government.
Received November 26, 2008. Accepted in final form March 6, 2009.
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Neurology 2009 73: 338-339.
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  R. A. Cohen and A. Gongvatana HIV-associated brain dysfunction in the era of HAART: Reasons for hope, but continued concern Neurology, August 4, 2009; 73(5): 338 - 339. [Full Text] [PDF]
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