Chronic alanine aminotransferase elevation in people with HIV : Time trends over 22 years and genetic predisposition

INTRODUCTION: Chronic elevation of alanine aminotransferase (cALT) is common in people with HIV. Published reports on cALT prevalence time trends have not been uniform. It is unknown whether genetic background is associated with cALT in people with HIV. METHODS: cALT was defined as ALT levels (male, >50 U/L, female, >35 U/L) at ≥2 consecutive, 6-monthly per protocol Swiss HIV Cohort Study (SHCS) visits. We calculated cALT prevalence plus trends in time-updated clinical and HIV-related cALT risk factors per calendar year in SHCS participants without viral hepatitis co-infection. In cALT cases and matched controls, we obtained uni- and multivariable odds ratios (ORs) for cALT, adjusting additionally for a polygenic risk score (PGS) associated with transaminase levels in the general population. RESULTS: Between 2002 and 2023, 8'909 SHCS participants contributed 203'832 ALT values obtained per protocol, and 8'414 cALT events occurred. The yearly cALT prevalence increased significantly (p < 0.001) from 7.5% (95% confidence interval, 6.3%-8.9%) in 2002 to the highest level of 10.1% (9.1%-11.1%) in 2005, followed by a significant (p < 0.001) decline to 5.3% (4.8%-5.9%) in 2018, with stable rates thereafter (p = 0.280). An increased multivariable cALT-OR was noted for obesity (OR = 2.84; 1.99-4.07), for 6-12-month exposure to non-nucleoside reverse transcriptase inhibitors (OR = 2.09; 1.09-4.03) and tenofovir disoproxil fumarate (OR = 1.99; 1.15-3.46). Participants with unfavourable genetic background (top vs. bottom quintile of PGS) had a multivariable-adjusted cALT-OR of 4.44 (3.09-6.39). CONCLUSION: cALT prevalence has decreased by almost half in people with HIV in Switzerland since 2005. Unfavourable genetic background is a strong independent risk factor for cALT.