Background: clinically relevant methods to identify individuals at risk for impaired daily living abilities secondary to neurocognitive impairment (ADLs) remain elusive. This is especially true for complex clinical conditions such as HIV-Associated Neurocognitive Disorders (HAND). The aim of this study was to identify novel and modifiable factors that have potential to improve diagnostic accuracy of ADL risk, with the long-term goal of guiding future interventions to minimize ADL disruption. Methods: study participants included 79 people with HIV (PWH; mean age = 63; range = 55À80) enrolled in neuroHIV studies at University California San Francisco (UCSF) between 2016 and 2019. All participants were virally suppressed and exhibited objective evidence of neurocognitive impairment. ADL status was defined as either normative (n = 39) or at risk (n = 40) based on a task-based protocol. Gradient boosted multivariate regression (GBM) was employed to identify the combination of variables that differentiated ADL subgroup classification. Predictor variables included demographic factors, HIV disease severity indices, brain white matter integrity quantified using diffusion tensor imaging, cognitive test performance, and health co-morbidities. Model performance was examined using average Area Under the Curve (AUC) with repeated fivefold cross validation. Findings: the univariate GBM yielded an average AUC of 83% using Wide Range Achievement test 4 (WRAT-4) reading score, self-reported thought confusion and difficulty reading, radial diffusivity (RD) in the left external capsule, fractional anisotropy (FA) in the left cingulate gyrus, and Stroop performance. The model allowing for two-way interactions modestly improved classification performance (AUC of 88%) and revealed synergies between race, reading ability, cognitive performance, and neuroimaging metrics in the genu and uncinate fasciculus. Conversion of Neuropsychological Assessment Battery Daily Living Module (NAB-DLM) performance from raw scores into T scores amplified differences between White and non-White study participants. Interpretation: demographic and sociocultural factors are critical determinants of ADL risk status among older PWH who meet diagnostic criteria for neurocognitive impairment. Task-based ADL assessment that relies heavily on reading proficiency may artificially inflate the frequency/severity of ADL impairment among diverse clinical populations. Culturally relevant measures of ADL status are needed for individuals with acquired neurocognitive disorders, including HAND.