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. Pricefor the INSIGHT START Neurology Substudy Group

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9 Citations (Scopus)


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
Pages (from-to)985-997
Number of pages13
Issue number8
Publication statusPublished - 15 May 2018


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

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