Modeling deficits in attention, inhibition, and flexibility in HAND

Nearly half of all HIV-1-positive individuals on combination antiretroviral therapy (cART) are afflicted with HIV-1-associated neurocognitive disorders (HAND). The most prevalent cognitive deficits observed in the cART era are those of attention and executive function. Presently, we sought to model deficits in attention and core components of executive function (inhibition, flexibility, and set-shifting) observed in HAND using the HIV-1 transgenic (Tg) rat, which expresses 7 of the 9 HIV-1 genes. Ovariectomized female Fischer HIV-1 Tg and non-transgenic control rats (ns = 39-43) were tested in a series of operant tasks: signal detection, discrimination learning, reversal learning, and extradimensional set-shifting. The HIV-1 Tg animals attained the criterion of three sessions at 70% accuracy at a significantly slower rate than the control animals on all tasks with the exception of the extradimensional set-shifting task. Of the animals that met the criteria, there was no significant difference in percent accuracy in any task. However, the HIV-1 Tg rats showed a lower overall response rate in signal detection and discrimination learning. A discriminant function analysis classified the animals by genotype with 90.4% accuracy based on select measures of their performance. The functional consequences of chronic low-level expression of the HIV-1 proteins on attention, as well as inhibition and flexibility as core components of executive function, are apparent under conditions which resemble the brain proinflammatory immune responses and suppression of infection in HIV-1+ individuals under cART. Deficits in attention and core components of executive function may reflect an underlying impairment in temporal processing in HAND.