Antiretroviral Treatment is Associated with Increased Attentional Load-Dependent Brain Activation in HIV Patients

Abstract

Objective-The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection.Methods-Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n=18), HIV subjects treated with antiretroviral medications (HIV+ ARV, n=12), or not treated with antiretroviral medications (HIV+NARV, n=12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging.Results-HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to . HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected=0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs.Interpretation-These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention. Prior functional magnetic resonance imaging (fMRI) studies demonstrated increased usage of reserve brain regions during working memory and attention tasks in HIV patients with mild dementia as well as in those who were neuroasymptomatic (Ernst et al. 2002). With effective antiretroviral treatments (ARVs), HIV-infected individuals are living longer, and the full clinical manifestation of HIV-dementia is less common (Dore et al. 2003;Ghafouri et al. 2006). However, the prevalence of a milder form of cognitive impairment appears to be rising among HIV-infected individuals, possibly due to the longer duration of illness and the additional effect of aging in these patients. Although treatment with ARVs typically leads to improved cognitive performance in HIV patients with dementia or cognitive deficits (Larussa et al. 2006;Sacktor et al. 2006;Sacktor et al. 2000), some studies suggest that some ARV treatments may not benefit the cognitive performance of those with lower nadir CD4 counts (Cysique et al. 2006). In addition, patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy (Dalakas 2001); however, the effects of these drugs on brain function are not well understood. As NRT...

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