Metabolic dysfunction-associated steatotic liver disease linked to antiretroviral exposure in cohort of people with HIV

Objectives: – To examine the association between exposure to antiretroviral therapy (ART) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a Danish cohort of people living with human immunodeficiency virus (PWH). Design: – Cross-sectional observational study. Methods: – MASLD was defined as a transient elastography-derived Continuous Attenuation Parameter ≥275 dB/m and ≥1 cardiometabolic risk factor. We analyzed associations between MASLD and exposure to ARTs using multivariable logistic regression, adjusted for age, sex, BMI, HIV diagnosis duration, diabetes, and comorbidity burden. ART use was categorized as none, past, or current. Non-linearity of cumulative exposure was assessed by comparing linear versus quadratic terms via a likelihood ratio test to select the final model. Results: – The prevalence of MASLD was 29.5% in 397 participants. Current bictegravir use was associated with higher odds of MASLD (aOR = 2.41; 95%CI: 1.15–5.04), while current use of nevirapine was associated with lower odds of MASLD (aOR = 0.26; 95%CI: 0.08–0.85). Similarly, cumulative exposure to bictegravir, tenofovir alafenamide (TAF), and ritonavir or cobicistat boosted atazanavir was associated with MASLD. The relationship was inversely U-shaped for bictegravir and TAF with increasing predicted probability of MASLD up to 2.1 years of cumulative bictegravir exposure, for TAF up to 2.7 years of cumulative exposure. Cumulative exposure to boosted atazanavir was associated with higher odds of MASLD (aOR = 1.09; 95%CI: 1.01–1.18). Conclusion: – Our findings suggest that commonly used antiretrovirals may contribute to the development of MASLD. Prospective studies examining the possible causal effects of these therapies on MASLD development and progression are warranted.