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

## TL;DR

People with HIV who have a history of methamphetamine use show altered brain activity when making risky choices, suggesting combined effects on decision-making.

## Contribution

The study reveals compensatory brain activation in PWH with methamphetamine use disorder during risky decision-making tasks.

## Key findings

- PWH with a history of METH use disorder showed greater ACC and caudate activation during risky choices.
- Longer HIV infection duration was linked to increased ACC activation to risky choices in PWH.
- Combined HIV and METH effects on decision-making regions may not be additive.

## Abstract

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.