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Chapter 2 : Evolution of Neuropsychological Issues in HIV-1 Infection during the HAART Era
Category: Viruses and Viral Pathogenesis
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This chapter summarizes the neuropsychological (NP) findings from the highly active antiretroviral therapy (HAART), and pre-HAART eras, including a discussion of the impact that impairment has on “real-world” functioning. Reports from a number of cohorts suggest that, in the HAART era, a subset of individuals transition in and out of impairment over time, raising the possibility that neurocognitive dysfunction in HIV-1 infection may be neither static nor chronically progressive but in the mildest forms may exhibit a fluctuating, relapsing/remitting course, similar to demyelinating disorders. HIV-1 infection of the brain is characterized by HIV encephalitis (HIVE), or the presence of multinucleated giant cells, microglial nodules, astrocytosis, and myelin pallor. Importantly, in the Heaton and coworkers study, both the NP and functional batteries were independent predictors of “real-world” functional status, based on complaints of cognitive difficulties, level of dependence/independence in instrumental activities of daily living, and employment status. Several brief cognitive screening techniques have been developed for situations in which a full or focused NP evaluation is not indicated or not feasible. Most research studies of NP function in HIV-1 infection utilize between-group mean comparisons of test scores on individual measures. Some controversy still exists regarding whether affective/ mood disorders, such as major depression and anxiety, interact with neurocognitive impairment. Ivnik and coworkers showed that large positive and negative test score changes were not uncommon for individuals across time, even though test-retest means stay relatively stable across the entire sample.
Estimate for distribution of time to neurocognitive impairment (in years) on or prior to 31 December 1995 (pre-HAART) versus on or after 1 January 1996 (post-HAART). (From Deutsch et al., 2001 .)
Reduction (improvement) in NP performance (GDS) among subjects with and without suppressed CSF HIV RNA viral load at follow-up. The box-and-whisker plots show the median (center line), interquartile range (box), and 5th and 95th percentiles (whiskers). (From Letendre et al., 2004 .)
Relationship between dendritic complexity in the midfrontal region and blinded clinical rating of global neurocognitive functioning. (From Masliah et al., 1997 .)
Performances of HIV– (open columns), HIV+ NP normal (gray columns), and HIV+ NP impaired (black columns) subjects on driving simulator measures of accidents and navigational errors and an on-road driving evaluation. (Adapted from Marcotte et al., 2004 .)
Neuropsychological tests in the current HNRC battery