A History of Methamphetamine Use Disorder in People with HIV Is Associated with Altered Functional Response to Risky Choice.

Methamphetamine (METH) use is highly prevalent among people with HIV (PWH) and those at risk and may contribute to overall worse health outcomes. Poorer health-related problems may be mediated by METH enhancing risky decision-making among PWH. While both METH and HIV are known to have overlapping and deleterious effects on the frontostriatal neural circuitry essential for decision-making, few studies have examined their combined effects. Eighty-eight participants stratified by HIV and a history of METH use disorder completed a risky decision-making paradigm, which involved choosing among safe (20¢) and risky (40¢/80¢ win or loss) choices, during blood-oxygen level-dependent functional magnetic resonance imaging (fMRI). Linear mixed-effects models were used to assess voxelwise differences in group and choice constrained to the anterior cingulate cortex (ACC), insula, and striatum. Despite similar choice behavior across groups, PWH and a history of METH use disorder had greater activation of the ACC and caudate than either condition alone (i.e., HIV+/METH- and HIV-/METH+), which was similar to seronegative, non-using controls. Within the ACC in particular, these differences may have been driven by safe choices. A longer estimated duration of HIV infection was associated with greater ACC activation to risky choices for PWH regardless of METH use history. These findings suggest that PWH and a history of METH use disorder may exhibit compensatory activation of regions associated with decision-making in the context of rewards and that the effects of HIV and past METH use might not be additive.