Improved neurocognitive test performance in both arms of the SMART study: Impact of practice effect

Birgit Grund, Edwina J. Wright, Bruce J. Brew, Richard W. Price, Mollie P. Roediger, Margaret P. Bain, Jennifer F. Hoy, Judith C. Shlay, Michael J. Vjecha, Kevin R. Robertson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


We evaluated factors associated with improvement in neurocognitive performance in 258 HIV-infected adults with baseline CD4 lymphocyte counts above 350 cells/mm3 randomized to intermittent, CD4-guided antiretroviral therapy (ART) (128 participants) versus continuous therapy (130) in the Neurology substudy of the Strategies for Management of Antiretroviral Therapy trial. Participants were enrolled in Australia, North America, Brazil, and Thailand, and neurocognitive performance was assessed by a five-test battery at baseline and month 6. The primary outcome was change in the quantitative neurocognitive performance z score (QNPZ-5), the average of the z scores of the five tests. Associations of the 6-month change in test scores with ART use, CD4 cell counts, HIV RNA levels, and other factors were determined using multiple regression models. At baseline, median age was 40 years, median CD4 cell count was 513 cells/mm3, 88 % had plasma HIV RNA ≤400 copies/mL, and mean QNPZ-5 was -0.68. Neurocognitive performance improved in both treatment groups by 6 months; QNPZ-5 scores increased by 0.20 and 0.13 in the intermittent and continuous ART groups, respectively (both P < 0.001 for increase and P = 0.26 for difference). ART was used on average for 3.6 and 5.9 out of the 6 months in the intermittent and continuous ART groups, respectively, but the increase in neurocognitive test scores could not be explained by ART use, changes in CD4, or plasma HIV RNA, which suggests a practice effect. The impact of a practice effect after 6 months emphasizes the need for a control group in HIV studies that measure intervention effects using neurocognitive tests similar to ours.

Original languageEnglish (US)
Pages (from-to)383-392
Number of pages10
JournalJournal of neurovirology
Issue number4
StatePublished - Aug 2013

Bibliographical note

Funding Information:
The study was funded by NIH grants U01-AI4636 (National Institute of Mental Health [NIMH] and the National Institute of Neurological Disorders and Stroke [NINDS]), U01AI042170, and U01AI46362 (National Institute of Allergy and Infectious Diseases [NIAID]). We gratefully acknowledge the contributions of participants, investigators, and staff who were crucial to the success of the study. Clinical sites and investigators participating in the SMART Neurology substudy were published (Wright et al. ).

Funding Information:
The following authors received research support from the NIH: BG and MPR from NIH/NIAID (U01-AI068641, U01-AI042170, and U01-AI46362); EJW (NIMH/NINDS 1U01-AI068641); BJB (R01 NS43103); RWP (NIDA P01DA026134, NIMH R01-MH62701, NIMH R21-MH083520, NIMH U01-MH083545, NIMH R01MH081772, NIMH/NIAIDU01-AI068641, and NIMH/NIAID U01-AI38858); and KRR (NIAID, supplement to 1U01AI068636-01, NIMH MH067751, NIAID U01-AI068641, and NINDS R21NS0692). MPB, JH, JCS, and MJV declare that they have no conflicts of interest.


  • HIV
  • Learning effect
  • Neurocognitive performance
  • Neuropsychological tests
  • Practice effect
  • Test-retest


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