Biopsychosocial phenotypes in people with HIV in the CHARTER cohort

Neuropsychiatric complications such as neurocognitive impairment and depression are common in people with HIV despite viral suppression on antiretroviral therapy, but these conditions are heterogeneous in their clinical presentations and associated disability. Identifying novel biopsychosocial phenotypes that account for neurocognitive performance and depressive and functional symptoms will better reflect the complexities encountered in clinical practice and may have pathological and therapeutic implications. We classified 1580 people with HIV based on 17 features, including 7 cognitive domains, 4 subscales of the Beck depression inventory-II, 5 components of the patient's assessment of own functioning inventory, and dependence in instrumental and basic activities of daily living. A two-stage clustering procedure consisting of dimension reduction with self-organizing maps and Mahalanobis distance-based k-means clustering algorithms was applied to cross-sectional data. Baseline demographic and clinical characteristics were compared between the phenotypes, and their prediction on the biopsychosocial phenotypes was evaluated using multinomial logistic regression. Four distinct phenotypes were identified. Participants in Phenotype 1 overall did well in all domains. Phenotype 2 had mild-to-moderate depressive symptoms and the most substance use disorders. Phenotype 3 had mild-to-moderate cognitive impairment, moderate depressive symptoms, and the worst daily functioning; they also had the highest proportion of females and non-HIV conditions that could affect cognition. Phenotype 4 had mild-to-moderate cognitive impairment but with relatively good mood, and daily functioning. Multivariable analysis showed that demographic characteristics, medical conditions, lifetime cocaine use disorder, triglycerides, and non-antiretroviral therapy medications were important variables associated with biopsychosocial phenotype. We found complex, multidimensional biopsychosocial profiles in people with HIV that were associated with different risk patterns. Future longitudinal work should determine the stability of these phenotypes, assess factors that influence transitions from one phenotype to another, and characterize their biological associations.