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

Abstract

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.

Fig. 1

Study design, CONSORT flow diagram, and use of antiretroviral treatment (ART)

Fig. 2

a Change in QNPZ-5 and z scores from baseline to month 6, with 1 SE indicated by error bars. b Change in QNPZ-5 scores within subgroups by ART status, and mean CPE rank of ART at baseline and month 6. *P≤0.05, increase in z score is statistically significant (for two-sided t test); **P<0.01; ***P<0.001. Superscript letter a estimated difference 0.05 (P=0.40) after adjustment for change in CD4 and HIV RNA. CPE Rank CNS penetration rank of ART (Letendre et al. 2010), CT Color Trails tests, FT Finger Tapping test (nondominant hand), GPB Grooved Pegboard (dominant hand), QNPZ-5 quantitative neurocognitive performance z score, TG Timed Gait test