No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts

Edwina J. Wright, Birgit Grund, Kevin R. Robertson, Lucette Cysique, Bruce J. Brew, Gary L. Collins, Mollie Poehlman-Roediger, Michael J. Vjecha, Augusto César Penalva De Oliveira, Barbara Standridge, Cate Carey, Anchalee Avihingsanon, Eric Florence, Jens D. Lundgren, Alejandro Arenas-Pinto, Nicolas J. Mueller, Alan Winston, Moses S. Nsubuga, Luxshimi Lal, Richard W. Price

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Objective: To compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with more than 500 CD4 + cells/μl. Design: Randomized trial. Methods: The START parent study randomized participants to commence immediate versus deferred ART until CD4 + less than 350 cells/μl. The START Neurology substudy used eight neuropsychological tests, at baseline, months 4, 8, 12 and annually, to compare groups for changes in test performance. Test results were internally standardized to z-scores. The primary outcome was the average of the eight test z-scores (QNPZ-8). Mean changes in QNPZ-8 from baseline were compared by intent-to-treat using longitudinal mixed models. Changes from baseline to specific time points were compared using ANCOVA models. Results: The 592 participants had a median age of 34 years; median baseline CD4 + count was 629 cells/μl; the mean follow-up was 3.4 years. ART was used for 94 and 32% of accrued person-years in the immediate and deferred groups, respectively. There was no difference between the immediate and deferred ART groups in QNPZ-8 change through follow-up [-0.018 (95% CI -0.062 to 0.027, P = 0.44)], or at any visit. However, QNPZ-8 scores increased in both arms during the first year, by 0.22 and 0.24, respectively (P < 0.001 for increase from baseline). Conclusion: We observed substantial improvement in neurocognitive test performance during the first year in both study arms, underlining the importance of using a control group in studies assessing neurocognitive performance over time. Immediate ART neither benefitted nor harmed neurocognitive performance in individuals with CD4 + cell counts above 500 cells/μl.

Original languageEnglish (US)
Pages (from-to)985-997
Number of pages13
Issue number8
StatePublished - May 15 2018

Bibliographical note

Funding Information:
NIH grants: UM1-AI068641 and UM1-AI120197, NINDS/NIMH (funding provided via START NIH grant).

Funding Information:
Funding: The parent START study was supported by the National Institute of Allergy and Infectious Diseases (United States), Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundesministerium für Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and the University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck. Additionally, the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke (United States) specifically funded the START Neurology substudy.

Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.


  • HAND
  • HIV
  • antiretroviral treatment
  • central nervous system
  • neurocognitive impairment


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