Neurocognitive impairment (NCI) in people living with HIV (PLWH) remains a concern despite combined antiretroviral therapy (cART). Higher Central nervous system Penetration Effectiveness (CPE) scores have been associated with better central nervous system HIV replication control, but the association between CPE and NCI remains controversial.

To analyse the potential association between Central nervous system Penetration Effectiveness (CPE) scores of antiretroviral agents and neurocognitive impairment (NCI) in people living with HIV.

The Neurocognitive Assessment in the Metabolic and Aging COhort (NAMACO) study, a sub-group of the Swiss HIV Cohort Study (SHCS), enrolled 909 HIV-positive aviraemic SHCS participants aged ≥45 years. All participants underwent standardized neurocognitive assessment. Cross-sectional CPE scores (at neurocognitive assessment) and cumulative CPE scores (summarizing CPE scores from cART initiation to the time of neurocognitive assessment) were examined as potential predictors of NCI in multivariate logistic regression models.

Most patients were male (80%) and Caucasian (92%). All had undetectable plasma HIV-RNA at neurocognitive assessment. NCI was present in 40%, of whom 26.4% had HIV-associated NCI: 25% with asymptomatic neurocognitive impairment, 0.8% with mild neurocognitive disorder and 0.6% with HIV-associated dementia. None of the CPE scores, neither cross-sectional nor cumulative, was statistically significantly associated with NCI.

In this large and well-treated HIV-positive cohort, a quarter of the population were diagnosed with HIV-associated NCI. We observed no association between NCI and cross-sectional or the novel cumulative CPE scores.