Predictors of Liver Steatosis Progression Among People Living With HIV in Low‐ and Middle‐Income Countries: A Multicentre Longitudinal Study

ABSTRACT Introduction Liver steatosis is increasingly recognized as a major comorbidity in people living with HIV (PLWH), with growing evidence suggesting an increased risk of progression to advanced liver disease. We assessed predictors of liver steatosis progression over 36 months in PLWH from low‐ and middle‐income countries. Methods Between 2020 and 2023, we enrolled PLWH aged ≥40 years who had been on antiretroviral therapy (ART) for ≥6 months at nine HIV clinics in the IeDEA Sentinel Research Network (SRN) across the Asia‐Pacific, the Americas and African IeDEA regions, and followed them prospectively for 36 months. Participants with available and reliable controlled attenuation parameter (CAP) measurements at both enrolment and the 36‐month visits were included in the analysis. Steatosis progression was defined as incident steatosis (CAP ≥248 dB/m) or a transition to a higher steatosis grade (moderate ≥268 dB/m; severe ≥280 dB/m) among those with a lower steatosis grade at enrolment. Logistic regression was used to assess predictors of progression. Results We included 923 participants (63% female; median age 50 years, interquartile range 45–55) in this analysis. At enrolment, 51% were overweight or obese, 10% had type 2 diabetes mellitus (T2DM), 94% had HIV RNA <1000 copies/mL and 72% were on integrase strand inhibitor (INSTI)‐based ART. During the 36‐month follow‐up, 190 (20%) participants showed steatosis progression, including 147 (74%) with incident steatosis and 49 (26%) with worsening of steatosis grades. The progression rate was significantly higher in Asia‐Pacific (33% [95% CI, 24−44]) and the Americas (36% [95% CI, 26−46]) compared to the African regions (17% [95% CI, 14−20]). Independent predictors of steatosis progression were overweight/obesity (aOR: 2.97, 95% CI: 2.03−4.40), T2DM (aOR: 2.41, 95% CI: 1.45−3.96) and dyslipidaemia (aOR: 1.46, 95% CI: 1.01−2.12). In females, INSTI use for ≥2 years at enrolment was additionally associated (aOR 3.19, 95% CI: 1.35−8.01). Conclusions Metabolic disorders—including T2DM, overweight/obesity and dyslipidaemia—were associated with steatosis progression in PLWH in our cohort. These findings underscore the need for targeted monitoring and prevention strategies to address this significant public health issue.