The impact of dolutegravir on depressive side effects: A multivariate analysis of age, gender, anti‐depressant use and race in charter cohort of people with HIV

23 Background: Integrase strand transfer inhibitors (InSTIs) are first-line therapy in the United States and other countries. One InSTI drug, dolutegravir (DTG), has been linked to neuropsychiatric adverse events, but few reports have used standardized assessments of depression or assessed the concomitant influence of age and antidepressant use. The aim of these analyses was to determine the relationships between InSTI use, ageing, antidepressant use and depressive symptoms in people with HIV (PWH). Methods: All 280 participants were comprehensively assessed in the CHARTER Ageing project, were taking ART and had plasma HIV RNA ≤ 200 copies/mL. The project enrolled participants based on chronological age < or ≥60 years. The Beck Depression Inventory (BDI)-II and four subscales were compared to demographic characteristics, use of InSTIs and antidepressants and clinical biomarkers in a cross-sectional design by multivariable linear regression, including backward selection by Akaike Information Criterion. Results: Participant characteristics included median age 56 years (28.7% > 60), 18.3% female, 38.8% black, 71.7% AIDS, median CD4 + T-cells 625/μL, median duration of the current ART regimen 19.4 months and 67.8% InSTI use. Overall, InSTI use was not associated with BDI-II, but DTG use trended toward association with worse BDI-II scores (p = 0.064). Multivariable analysis identified that non-Black race (p = 0.0033), DTG use (p = 0.0042), female sex (p = 0.011), antidepressant use (p = 0.039) and age ≥ 60 (p = 0.056) were associated with worse BDI-II scores. The effects of DTG were present in the Apathy (p = 0.0027), Cognitive (p = 0.019) and Somatic (p = 0.020) BDI-II subscales. Interaction analyses identified that DTG was associated with worse BDI-II principally among those older than 60 years (interaction p = 0.026; see Figure). Conclusions: DTG may increase depressive symptoms in older PWH and those who use an antidepressant. Additionally, DTG worsened depressive symptoms in females or non-Black individuals. Others have reported neuropsychiatric adverse events associated with DTG, but this is the first study to use a standardized depression assessment and to identify an interaction with antidepressants, which may provide mechanistic and clinical insights to improve the care of PWH.