Objective: To determine whether treatment with ritonavir-boosted protease inhibitor (PI) monotherapy is associated with detrimental effects on neurocognitive function or brain imaging markers compared to standard antiretroviral therapy (ART).

Methods: Neuropsychological assessment and brain magnetic resonance imaging were performed at the last study visit in a subset of participants randomised to PI monotherapy (PI-mono group) or ongoing triple ART (OT group) in the PIVOT trial. We calculated a global z-score (NPZ-7) from the average of the individual test z-scores and the proportion of participants with symptomatic neurocognitive impairment (score >1 standard deviation (SD) below normative means in ≥2 cognitive domains and neurocognitive symptoms). In a subgroup, white matter hyperintensities, bicaudate index, global cortical (GCA) and medial temporal lobe atrophy scores and single voxel (basal ganglia) N-acetylaspartate (NAA)/Choline, NAA/Creatine and myo-inositol/Creatine ratios were measured.

Results: 146 participants (75 PI-mono) had neurocognitive testing (median time after randomisation 3.8 years), of whom 78 were imaged. We found no difference between arms in NPZ-7 score (median -0.4 (Interquartile range (IQR)=-0.7; 0.1) vs -0.3 (IQR=-0.7; 0.3) for the PI-mono and OT groups respectively, p=0.28), the proportion with symptomatic neurocognitive impairment (13% and 18% in the PI-mono and OT groups respectively; p=0.41), or any of the neuroimaging variables (p>0.05). Symptomatic neurocognitive impairment was associated with higher GCA score (OR=6.2 per additional score; 95% confidence interval (CI)=1.7-22.3 p=0.005) but no other imaging variables.

Conclusions: Based on a comprehensive neuropsychological assessment and brain imaging, PI monotherapy does not increase the risk of neurocognitive impairment in stable HIV+ patients.