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Neuropsychological Performance is
Better in HIV-Infected Subjects Treated with Neuroactive HAART
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Reported by Jules Levin
17th CROI Feb 16-19 2010 SF
Fabrizio Starace1,2, Manuela de Stefano1,2, Antonietta D’Abrosca1, Miriam Gargiulo1, Antonio Chirianni1, 1CotugnoHospital, Naples, Italy, 2University of Naples SUN, Italy
Prof. Fabrizio Starace
Director, PsychiatricUnit,
CotugnoHospital
Via Quagliariello, 54 -Naples(IT)
Phone: +39 0815908202
Fax: +39 0815908430
E-mail: fabrizio.starace@tin.it
AUTHOR SUMMARY & CONCLUSIONS
A. In our sample of virally suppressed HIV-seropositive individuals, in stable HAART treatment and not exposed to other risk factors, neuropsychological performance was better in subjects taking neuroactive ARV drugs
B. Higher CPE ranks were strongly associated with better scores on tests measuring working memory, verbal fluency and executive functions
C. Moreover, ANI and MND prevalence was lower in high CPE group than in low CPE group
D. These findings suggest the need for routine neuropsychological screening to guide the optimal management of milder but potentially relevant cognitive impairment
E. Further studies should longitudinally evaluate the course of these deficits, to help identifying possible interventions and reducing the incidence of cognitive impairment in patients who achieve effective systemic viral suppression.
ABSTRACT
Background: The association between CNS Penetration Effectiveness (CPE) of ARV drugs and cognitive performance is still unclear. For example, in ACTG 736 study an inverse relationship was found between ARV therapy with good CNS penetration and neuropsychological performance. Here we report results from an exploratory case-control study carried out in virally suppressed HIV-seropositive individuals.
Methods: Trained research psychologists blind to ARV regimens administered the Cotugno Mini Battery (a brief neuropsychological battery including Verbal Memory Span, Auditory Verbal Learning Test Trial 1-5, Verbal Fluency, Color Trails 2, Symbol Digit Modalities Test and Timed Gait) to subjects admitted to care. For the purpose of this analysis, cases were included if they showed stable plasma viral suppression and had ART regimen unchanged for at least 6 months before assessment. Exclusion criteria were age > 60, formal educational < 8 years, depressive symptomatology(MADRS score > 15), other major neurological or psychiatric disorders, current use of illicit drugs. CNS penetration effectiveness score was calculated according to Italian National Guidelines for HIV Therapy. Subjects with higher CNS penetration effectiveness rank were compared with those with lower CNS penetration effectiveness rank (cut-off 2.0) in terms of performance on each neuropsychological test.
Results: We included 45 subjects in the analysis (80% male; median age 42 years; median years of education 11); 15 patients were on ART regimen with a high CNS penetration effectiveness score (>2). As compared to those with a low CNS penetration effectiveness score, they showed a better performance on Verbal Memory Span (5.6 +1.3 vs4.8 +1.1; p < 0.05), Verbal Fluency (14.7 +9.9 vs9.8 +4.6; p <0.05), Symbol Digit Modalities Test (44.4 +16.4 vs34.6 +11.4; p <0.05). No significant difference was found on other tests.
Conclusions: In this sample of virally suppressed HIV individuals in stable HAART and not exposed to other risk factors, neurocognitive performance was better in subjects taking neuroactive ART drugs on measures of working memory, verbal fluency, and executive functions. Findings suggest the need for routine neurocognitive screening to guide the optimal management of milder but potentially relevant neuropsychological deficits. Future studies should longitudinally evaluate the course of these deficits to help identify possible interventions aiming to reduce the incidence of neurocognitive impairment in patients who achieved effective systemic viral suppression.
BACKGROUND
HAART has led to long-lasting suppression of systemic HIV replication in most HIV-seropositivepersons. However, the prevalence of HIV associated Neurocognitive Disorders (HAND) is reported to be stable or even increased. Poor CNS penetration of antiretroviral (ARV) drugs has been considered amongpossible explaining factors, though the association between CNS Penetration Effectiveness (CPE) of ARV drugs and cognitive performance is still unclear.
THE AIM of this study was to evaluate whether HAART penetration into the CNS, estimated by CPE rank, is associated with better neuropsychological performances and lower HAND prevalence in HIV subjects.
METHODS
Trained research psychologists, blind to ARV regimens, administered the Cotugno Mini Battery (Table 4) to 85 HIV patients consecutively admitted to DH at CotugnoHospital, Naples.
For the purpose of this analysis, cases were included if they showed stable plasma viral suppression and had ARV regimen unchanged for at least 6 months before assessment.
Exclusion criteria were age > 60, education years < 8, prominent depressive symptoms (MADRS score > 15), other major neurological or psychiatric disorders, current drug abuse.
CPE score was assessed according to Italian National Guidelines for HIV Therapy.
Subjects with higher CPE rank were compared with those with lower CPE rank(cut-off = 2.0) in terms of performance on each neuropsychological test and of prevalence of HAND.
RESULTS
45 subjects were included in the analysis. 15 patients were on HAART regimen with a high CPE score (>2) (Table 1). As compared to those with lower CPE score, they showed a better performance on Verbal Memory Span (p < 0.05), Verbal Fluency (p < 0.05) and Symbol Digit Modalities Test (p < 0.05). No significant difference was found on other tests (Table 2). Moreover, the prevalence of HIV-associated Asymptomatic Neurocognitive Impairment (ANI) and of Minor Neurocognitive Disorder (MND) was significantly lower in the group on HAART with high CPE score (Table 3).
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