The effect of efavirenz on reward processing in asymptomatic people living with HIV: a randomized controlled trial.

Functional MRI studies have demonstrated that HIV-infection affects the fronto-striatal network. It has not been examined what impact efavirenz, an antiretroviral drug notorious for its neurocognitive effects, has on the reward system: a key subcomponent involved in depressive and apathy symptoms. Therefore, this study aims to investigate the effect of efavirenz on reward processing using a monetary incentive delay task. In this multicenter randomized controlled trial, asymptomatic adult participants stable on emtricitabine/tenofovirdisoproxil/efavirenz (FTC/TDF/EFV) were randomly assigned in a 2:1 ratio to switch to emtricitabine/tenofovirdisoproxil/rilpivirine (FTC/TDF/RPV) (n=30) or continue taking FTC/TDF/EFV (n=13). At baseline and twelve weeks after therapy switch, both groups performed a monetary incentive delay task. Behavior and functional brain activity related to reward anticipation and reward outcome were assessed with blood oxygen level dependent functional MRI. Both groups were matched for age, education-level and time since HIV-diagnosis and on EFV. At the behavioral level, both groups had faster response times and better response accuracy during rewarding versus non-rewarding trials, with no improvement resulting from switching FTC/TDF/EFV to FTC/TDF/RPV. No significant change in activation related to reward anticipation in the ventral striatum was found after switching therapy. Both groups had significantly higher activation levels over time, consistent with a potential learning effect. Similar activity related to reward outcome in the orbitofrontal cortex was found. Discontinuing FTC/TDF/EFV was not found to improve activity related to reward anticipation in asymptomatic people living with HIV, with similar cortical functioning during reward outcome processing. It is therefore likely that EFV does not affect motivational control. Further research is needed to determine whether EFV affects motivational control in HIV populations with different characteristics.