Long-term trajectories of Hepatic and Metabolic biomarkers after switching from TDF to TAF in ART-Experienced PWH with and without Hepatic Coinfection: Data from the ICONA Cohort.

Objective: Long-term effects of switching from Tenofovir Disoproxil Fumarate (TDF) to Tenofovir Alafenamide (TAF) on hepatic, renal, and metabolic parameters remain poorly characterized, especially in people with HIV (PWH) and HBV coinfection.

Methods: We analyzed 24-month trajectories before and after the switch to TDF/TAF in ART-experienced, virologically suppressed participants from the ICONA cohort, excluding those who started antiviral treatment or had detectable HCV-RNA during the study period. Mean values at 18 (T_-18) and 6 months (T_-6) pre-switch, at switch, and 6, 12, and 24 months post-switch (T₊₆, T₊₁₂, T₊₂₄) were assessed using adjusted mixed linear models.

Results: At 6 months, Alanine Aminotransferase (ALT) decreased modestly by -3.05 [-6.42, 0.31] U/L, remaining stable at T+24; similar toother liver damage markers. In participants with chronic liver enzyme elevation, ALT reductions were more marked (-20.5 to -22.6 U/L from T₊₆ to T₊₂₄). Total cholesterol, LDL-Cholesterol, and triglycerides increased by 14.46, 10.70, and 11.56 mg/dL, respectively, at T₊₆, and then stabilized thereafter. PWH with baseline LDL-Cholesterol <100 mg/dL showed larger LDL increases. Compared to HIV-monoinfected, HBsAg+ individuals had higher ALT and lower eGFR on TDF, differences attenuated after switching to TAF(p<0.001 and p=0.002). No lipid trajectory differences emerged by coinfection status.

Conclusions: Greater hepatic improvement was noticed after TDF to TAF switch in PWH with HBV coinfection, with no differences in lipid increases compared to monoinfected patients.