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Improved Cognitive Function in Immune Reconstituted Advanced AIDS Patients Is Associated with Maintenance of HIV Suppression
A McCutchan*1, J Wu2, P Williams2, K Robertson3, R Ellis1, S Koletar4, and J Currier5
1Univ. of California, San Diego, USA; 2Harvard Sch. of Publ. Hlth., Boston, MA, USA; 3Univ. of North Carolina at Chapel Hill, USA; 4Ohio State Univ., Columbus, USA; and 5Univ. of California, Los Angeles, USA
Background: Continuing HIV-induced brain damage during
otherwise successful HAART is plausible because of the limited CNS penetration by some antiretroviral drugs and is
supported by epidemiological and magnetic resonance spectroscopic studies. We
hypothesized that neuropsychological impairment might progress despite
successful HAART therapy in patients with a history of AIDS.
Methods: A
subset (n = 370) of the ACTG 362 cohort with CD4
<50 before and >100 after HAART has had 3 neuropsychological assessments in 96 weeks. Neuropsychological
impairment was diagnosed if performance of any subtest (Trails A and B and Digit-symbol) was 2 SD or more
below age- and education-adjusted means for a normal population. Prevalence of neuropsychological
impairment was estimated in the white group (n = 240), for whom such age- and education adjusted normative data
is available. Viral (plasma HIV RNA levels)
and immune (CD4 counts) correlates of
trends in raw NPZ3 scores for the entire study population were assessed by Generalized
Estimating Equations which adjusted for age, race/ethnicity, education, and
time.
Results: The
cohort was predominantly male (90%),
white (65%), mature (median age = 40),
and educated beyond high school (median = 14 years). At baseline neuropsychological assessment, most patients had good immune
recovery (mean CD4 = 230) and HIV suppression (65% <500; only 14% >20,000
RNA copies/mL). Prevalence of neuropsychological impairment declined from 20% at baseline (n = 226) to 14% at 48 weeks (n
= 194) and 12% at 96 weeks (n = 190).
Improving raw NPZ3 scores were associated with plasma HIV RNA levels of <500
and drops in levels from >500 to <500 over the prior 16 weeks, but not
with contemporaneous, 16 weeks prior, or lowest lifetime CD4 counts.
Conclusions: Prevalence
of cognitive impairment (neuropsychological
impairment) was estimated at 20% in
immune-reconstituted, advanced AIDS patients with prolonged immune recovery on
HAART. Improved neuropsychological performance over 2 years likely reflects practice effects (learning), but could also indicate continuing
recovery after more than 5 years of HAART. On average, improvement of NP
performance was associated with continued or improving control of plasma HIV
RNA levels, but not with levels of immunosuppression (CD4 counts). We conclude
that most advanced AIDS patients responding to HAART for prolonged periods do
not experience detectable cognitive decline. Improving cognitive performance
was associated with plasma HIV suppression, which appears to be critical to
maintaining or restoring cognitive function.
Keywords: cognitive impairment; central nervous system; neuropsychology
