Objective: To determine factors associated with baseline neurocognitive performance in HIV-infected participants enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) neurology substudy. Methods: Participants from Australia, North America, Brazil, and Thailand were administered a 5-test neurocognitive battery. Z scores and the neurocognitive performance outcome measure, the quantitative neurocognitive performance z score (QNPZ-5), were calculated using US norms. Neurocognitive impairment was defined as z scores <-2 in two or more cognitive domains. Associations of test scores, the QNPZ-5, and impairment with baseline factors including demographics and risk factors for HIV-associated dementia (HAD) and cardiovascular disease (CVD) were determined in multiple regression. Results: The 292 participants had a median CD4 cell count of 536 cells/mm, 88% had an HIV viral load ≤400 copies/mL, and 92% were taking antiretrovirals. Demographics, HIV, and clinical factors differed between locations. The mean QNPZ-5 score was-0.72; 14% of participants had neurocognitive impairment. For most tests, scores and z scores differed significantly between locations, with and without adjustment for age, sex, education, and race. Prior CVD was associated with neurocognitive impairment. Prior CVD, hypercholesterolemia, and hypertension were associated with poorer neurocognitive performance but conventional HAD risk factors and the CNS penetration effectiveness rank of antiretroviral regimens were not. Conclusions: In this HIV-positive population with high CD4 cell counts, neurocognitive impairment was associated with prior CVD. Lower neurocognitive performance was associated with prior CVD, hypertension, and hypercholesterolemia, but not conventional HAD risk factors. The contribution of CVD and cardiovascular risk factors to the neurocognition of HIV-positive populations warrants further investigation.
Bibliographical noteFunding Information:
Dr. Wright has served on a scientific advisory board for GlaxoSmithKline and receives research support from Gilead Sciences, Inc., Boehringer Ingelheim, Abbott, the National Health and Medical Research Council of Australia , and the NIH ( NIMH/NINDS 1U01-AI068641 [Study Chair]). Dr. Grund has received research support from the NIH/NIAID ( U01-AI068641 [Statistician], U01-AI042170 [Statistician], and U01-AI46362 [Statistician] ). Dr. Robertson has received speaker honoraria from GlaxoSmithKline, Abbott, Boehringer Ingelheim, and Clinical Care Options, and receives research support from the NIH (NIAID, supplement to 1U01AI068636-01 [PI], NIMH MH067751 [coinvestigator], NIAID U01-AI068641 [Co-PI], and NINDS R21NS0692 [coinvestigator]). Prof. Brew serves on scientific advisory boards for GlaxoSmithKline, ViiV Healthcare, Biogen Idec, and Merck Serono; has received funding for travel from Abbott; serves on the editorial boards of Open Virology, the International Journal for Tryptophan Research, Faculty of 1000 Medicine, the Journal of Neurovirology, and Neurobehavioral HIV Medicine; receives royalties from the publication of HIV Neurology (Oxford University Press, 2001) and Palliative Neurology (Cambridge University Press, 2006); has received speaker honoraria from GlaxoSmithKline, ViiV Healthcare, Boehringer Ingelheim, Abbott, and Biogen Idec; and receives/has received research support from Eli Lilly and Company, GlaxoSmithKline, ViiV Healthcare, Merck Serono, the National Health and Medical Research Council (NHMRC) of Australia , the NIH ( R01 NS43103, co-PI ), the University of New South Wales, and from St. Vincent's Clinic Research Foundation. Ms. Roediger has received research support from the NIH ( NIAID U01-AI068641 [Statistician], NIAID U01-AI042170 [Statistician], and NIAID U01-AI46362 [Statistician] ). Ms. Bain has received speaker honoraria from GlaxoSmithKline. Dr. Drummond and Dr. Vjecha report no disclosures. Prof. Hoy serves on scientific advisory boards for Gilead Sciences, Inc., Tibotec Therapeutics (Janssen), Merck Sharp & Dohme, and Bristol-Myers Squibb; has received speaker honoraria from Gilead Sciences, Inc.; and receives research support from the National Health and Medical Research Council of Australia, Gilead Sciences, Inc., Merck Sharp & Dohme, Tibotec Therapeutics, Bristol-Myers Squibb, and Boehringer Ingelheim. Ms. Miller and Dr. Penalva de Oliveira report no disclosures. Dr. Pumpradit has received funding for travel from Pfizer Inc. and has received research support from the Ministry of Public Health, Thailand. Dr. Shlay reports no disclosures. Dr. El-Sadr receives research support from the NIH/NIAID ( 5 U01 AI69466-04 [PI], 5 U01 AI69466-03S1 [PI], and R01AI083038-01 [PI] ). Dr. Price has received speaker honoraria from the International AIDS Society and receives research support from Merck and Co, and from the NIH ( NIDA P01DA026134 [Project PI], NIMH R01-MH62701 [PI], NIMH R21-MH083520 [PI],. NIMH U01-MH083545 [Consultant], NIMH R01MH081772 [coinvestigator], NIMH/NIAIDU01-AI068641 [Co-Chair Neurology substudy Protocol], and NIMH/NIAID U01-AI38858 [Co-Chair AACTG study]).
Study funding: Supported by the NIH ( NIMH/NINDS U01-AI4636, NIAID U01AI042170, and NIAID U01AI46362 ).