Changes in alanine aminotransferase levels after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in HIV-positive people without viral hepatitis in the Swiss HIV Cohort Study. HIV Medicine
Kovari et al. assessed the impact of switching from TDF to TAF on alanine aminotransferase (ALT) in people with HIV. Authors included all patients without viral hepatitis on a stable antiretroviral therapy containing TDF who either switched to TAF, or remained on TDF. Changes in ALT were estimated using discontinuity regression with linear mixed effect models.
The study population included 1712 individuals, of whom 75% were male, and the median age was 50 years (IQR 42-57). At the time of switch, 11% of participants had elevated liver enzymes for 6 months or longer. Switching from TDF to TAF led to an adjusted decrease in ALT of 3.7 U/L (95% CI 3.2-4.2). Among individuals with abnormal ALT levels at the time of switch, replacing TDF with TAF was associated with a larger decrease in ALT (17 U/L) compared with individuals with a normal ALT (3.3 U/L). Results were similar across sensitivity analyses, and decreases in ALT were also observed in individuals who switched from TDF to a tenofovir-free dual-therapy. Authors found no relevant effect modifications of the ALT change by gender, age, transmission risk group or BMI.
Taken together, the present shows that switching from TDF to TAF among people with HIV but without viral hepatitis is associated with improvements in liver enzymes. Switching away from TDF – including to a tenofovir-free dual treatment – should be considered among people with HIV and unexplained chronically elevated transaminases. Due to the absence of effect modification by known risk factors for hepatotoxicity, the mechanisms behind the hepatotoxic potential of TDF and its long-term impact remain unclear.