-
Factors Associated with Persistent Neurocognitive Impairment
Despite Long-term HAART in Patients with HIV-DementiaV Tozzi, P
Balestra, MF Salvatori, C Vlassi, A Corpolongo, R Bellagamba, P
Lorenzini, S Galgani, M Zaccarelli, G Liuzzi, L Giancola, U
Visco-Comandini, E Boumis, A Antinori, P Narciso. National
Institute for Infectious Diseases "L. Spallanzani", Via Portuense
292, 00149 Rome, Italy. *Contact e-mail: [email protected]
optimal treatment for HIV-D has not been established, but there are
strong evidences that the highly active antiretroviral therapy
(HAART) is effective in treating the neurocognitive impairment
(NCI). However, although potent antiretroviral treatment can
reverse HIV-D, the benefits vary substantially between individuals.
In the era of HAART, the course of HIV-D has changed, and several
distinct patters of evolution of cognitive functions have been
proposed. Although these patterns have not been fully
characterized, they include: 1) improvement of cognitive functions
with full reversal of the cognitive deficit (reversible NCI), 2a)
initial improvement after the initiation of HAART but with
significant persistent neurological deficit, or 2b) slow continued
decline in neurocognitive functions with or without effective
peripheral virological control (persistent NCI). Thus, although
HAART improves NCI, predictors of reversible NCI are unknown.
Therefore, we have conducted a prospective observational study to
examine the clinical course of HIV associated NCI in patients with
HIV-D treated with HAART. Aims To describe prevalence of persistent
neurocognitive impairment despite long-term HAART in patients with
HIV-D. To assess and risk factors for persistent neurocognitive
impairment despite long-term HAART in patients with
HIV-D.MethodsDesign. Prospective observational study.Setting.
National Institute for Infectious Diseases, L Spallanzani, Rome,
Italy.Patients. All patients with HIV-related NCI (as defined
below) seen in our Institute since 1995. Exclusion criteria.
Opportunistic infections or tumors of the CNS, any confounding
neurological illness, major neurological or psychiatric disorders,
current drug abuse, use of sedative-hypnotics. Neuropsychological
testing. A battery of 17 standardized tests sensitive to a wide
spectrum of different cognitive domains. Administered by one of us
(P.B.). Requiring approximately 90 minutes to
complete.Neuropsychological (NP) testing z-scores. The NPl scores
from each test was transformed into a z-scores using a reference
population. Each z-score was adjusted so that negative values
indicated below-average performance. Summary global NPZ8 and NPZ4
scores were also ogtained. Neurological diagnosis. HIV-related
neurocognitive impairment (NCI) was defined as performing below one
standard deviation for the normative mean on at least two NP tests
or two standard deviations below the mean on at least one test. The
diagnosis of NCI also required the exclusion of other conditions
that could explain the finding. HAART regimens. As best judged by
the treating physician. Criteria for the diagnosis of either
reversible or persistent neurocognitive impairment (NCI). According
to the results of serial NP assessments, patients were considered
having either reversible or persistent NCI. End points.
Neuropsychological test results.Statistics. The Kaplan-Meier method
was used to estimate the probability of reversible neurocognitive
impairment over time. The association between reversible NCI and
selected characteristics was assessed by means of the chi-square
test, or, when appropriate, by means of the students t-test. A
multivariable analysis using a multiple logistic regression model
was performed in order to assess statistically significant
associations between reversible neurocognitive impairment and main
demographic (age, gender, years of education), clinical (HIV
disease stage at enrollment, virological response to HAART,
antiretroviral treatment, exposure to CSF penetrating drugs),
laboratory (CD4 cell count at enrollment and during follow-up,
plasma HIV RNA at enrollment and during follow-up), and
neuropsychological (NPZ4 and NPZ8 scores at enrollment and
follow-up) variables. Moreover, a multiple logistic regression was
also used to assess the probability of reversible neurocognitive
impairment adjusted by the same variables. AbstractE-119
Factors associated with reversible neurocognitive impairment
(NCI)Reversible NCI All patients No Yes p (n=116) (n=81) (n=35) Age
in years, mean (SD) 41.5 (8.4) 40.7 (8.0) 43.4 (9.0) .110Education
in years, mean (SD) 10.8 (3.9) 10.1 (3.6) 12.4 (4.4) .004Gender, n.
(%) female21 (18.1)20 (24.7) 2 (5.7) .017Months of follow-up, mean
(SD) 36.2 (27.7)35.6 (26.7)37.6 (30.0).725HIV transmission
modality, n. (%):- Intravenous drug use47 (40.2)37 (45.7)10 (28.6)-
MSM27 (23.1)17 (20.9)10 (28.6).408- Heterosexuality40 (35.0)25
(30.9)15 (42.3)- unknown2 (1.7) 2 (2.5) 0HIV clinical stage, n.
(%):- CDC group A or B56 (48.7) 35 (43.2)21 (60.0).148- CDC group
C60 (51.3)46 (56.8) 14 (40.0)Positive HCV serology, n. (%)56
(47.)44 (54.3)12 (34.3).231Baseline CD4 cell/ml, mean (SD) 259
(224) 268 (228) 238 (219).514Nadir CD4 cell/ml, mean (SD) 153 (137)
142 (116) 178 (174).205Bas viral load log cp/ml, mean (SD)3.93
(1.4)3.8 (1.5)4.3 (1.3).097Virological suppression (
-
Neuropsychological test battery, by cognitive domain
Concentration and Speed of Mental Processing
Trail Making A
WAIS-R Digit Span (forward)
WAIS-R Digit Span (backward)
WAIS-R Digit Symbol
Stroop Word and Colour
Corsi Cube test
Mental Flexibility
Trail Making B
Stroop Colour-Word
Stroop Colour-Word
Controlled Oral Word
Memory
Rey Auditory Verbal Learning
Rey Auditory Verbal Learning after 15
Rey Complex Figure, delayed
Figura Complessa di Rey, ritardata
Babcock Story Recall, immediate
Babcock Story Recall, delayed
Fine Motor Functioning
Lafayette Grooved Pegboard, dominant
Lafayette Grooved Pegboard, non domin.
Visuospatial and Constructional
Rey Complex Figure, copy
-
Neuropsychological testing:criteria for interpretation
Scores are adjusted for gender, age, education and compared to
population based norms. Criteria for impairment: >1 SD below the
normative mean on two tests or > 2 SD below the normative mean
on one test. Impaired patients: evaluation of other conditions that
could explain the finding (clinical, laboratory, neuroimaging).
Clinical evaluation of functional impairment. Diagnostic criteria
for HIV-D: impairment meeting or not meeting HIV-D criteria.
-
Delta changes from baseline in NPZ4* and NPZ8** scores in 68
HAART naive cognitively impaired patients, by month of HAART. *
Trail Making A, Trail Making B, Lafayette Grooved Pegboard dominant
hand, WAIS-R DigitSymbol** Trail Making A, Trail Making B,
Lafayette Grooved Pegboard dominant hand, Lafayette Grooved
Pegboard non dominant hand, WAIS-R Digit Span (backward), WAIS-R
DigitSymbol, Rey Auditory Verbal Learning Test, Rey Auditory Verbal
Learning after 15
* p
-
Delta changes from baseline in neuropsychological tests
exploring concentration and speed of mental processing in 68 HAART
naive cognitively impaired patients, by month of HAART.
* p
-
Delta changes from baseline in neuropsychological tests
exploring mental flexibility in 68 HAART naive cognitively impaired
patients, by month of HAART.
* p
-
Delta changes from baseline in neuropsychological tests
exploring memory in 68 HAART naive cognitively impaired patients,
by month of HAART.
* p
-
Delta changes from baseline in neuropsychological tests
exploring fine motor functioning in 68 HAART naive cognitively
impaired patients, by month of HAART.
* p
-
Proportion remaining impaired
Years since HAART
Kaplan-Meier estimates of the probability of remaining
cognitively impaired in the 116 cognitively impaired HIV+ patients,
by year of HAART
-
Abnormal Neuropsychological Test Battery results consistent with
HIV-related Neurocognitive Impairment
Exclusion of confounding conditions
HIV-related neurocognitive impairment(n=116 patients)
Serial neuropsychological assessments
Impaired Unimpaired (Persistent NCI) (Reversible NCI) n=81
(69.8%) n=35 (30.2%)
HAART
