HBV status modulates transaminase decrease after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in people with HIV

BACKGROUND: Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) has been associated with reduced transaminase level among people with HIV (PWH), with and without HBV. It is unclear whether the effect is mediated by HBV serostatus. METHODS: We conducted a longitudinal observational study of PWH who switched from TDF to TAF between 2016 and 2023. A mixed-effects model with random intercepts assessed the effect of the switch on transaminases, including an interaction term for HBV status: chronic hepatitis B (HBsAg+), possible occult HBV infection (pOBI; HBsAg-/HBcAb+) and no HBV. RESULTS: Among 727 individuals, 7% had chronic hepatitis B and 35% had pOBI. Switching to TAF was associated with a significant ALT decrease (β -3.5 UI/mL, 95%CI: -5.2 to -1.9). Compared to HBV-negative individuals, individuals with chronic hepatitis B experienced steeper ALT reduction (β -7.5, 95%CI: -11.8 to -3.2), while pOBI was associated with a non-significant reduction (β -1.9; 95%CI: -4.4-0.6; P = 0.133). These findings persisted after adjusting for other predictors of transaminase levels. TAF was also associated with accelerated weight gain (+0.75 kg/year, 95% CI: 0.63-0.87) and a transient drop in the Hepatic Steatosis Index (-0.22; 95% CI: -0.38 to -0.06) followed by an annual increase thereafter (+0.18/year; 95% CI: 0.10-0.27). CONCLUSIONS: Switching from TDF to TAF is associated with modest but statistically significant ALT reduction in PWH, especially in HBsAg + individuals. Our findings suggest that TAF may represent a favourable option in this subgroup, although potential metabolic consequences warrant close monitoring.