Case Report: When access is limited: using CYP3A4 inhibition to maintain clinical benefit from elexacaftor/tezacaftor/ivacaftor.

Introduction: Cystic fibrosis transmembrane conductance regulator modulators (CFTRm), particularly elexacaftor/tezacaftor/ivacaftor (ETI), have transformed outcomes for people with cystic fibrosis (pwCF). However, access remains limited globally due to genotype-based eligibility and high medication cost. Pharmacokinetic manipulation using cytochrome P450 3A4 (CYP3A4) inhibitors has emerged as a potential strategy to extend ETI exposure in resource-constrained settings. Case: We describe a 52-year-old female with CF (G542X/T1246I) whose genotype initially precluded subsidised ETI access in Australia. She experienced progressive clinical decline in 2024, with worsening bronchiectasis, recurrent Conclusion: This report supports the potential for CYP3A4 inhibition to aid with personalised ETI dosing strategies, particularly in low and middle-income countries where CFTRm access remains limited. Further research is needed to define optimal manipulation strategies, understand inter-individual variability in CFTRm metabolism, and evaluate the feasibility of therapeutic drug monitoring in diverse healthcare settings.