Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients.
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 SN (p-corrected = 0.006). 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.


CONCLUSIONS
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.
Chang
L
L
Department of Medicine, Division of Neurology, John A. Burns School of Medicine, University of Hawaii at Manoa, The Queen's Medical Center University Tower, 1356 Lusitana Street, Honolulu, HI 96813, USA. lchang@hawaii.edu
Yakupov
R
R
Nakama
H
H
Stokes
B
B
Ernst
T
T
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000503:physiopathology; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004359:Drug Therapy, Combination; D005625:Frontal Lobe / Q000503:physiopathology; D015497:HIV-1; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010296:Parietal Lobe / Q000503:physiopathology; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D011698:Pursuit, Smooth / Q000187:drug effects* / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors