Antiviral Treatment Failures After Transplantation of Organs From Donors With HCV Infection: A Report of 4 Cases.

The transplantation of organs from donors with hepatitis C virus (HCV) infection into uninfected recipients has expanded the available organ donor pool. With the advancement of direct acting antivirals (DAAs), high rates of cure among transplant recipients are possible. Although DAAs are highly effective, treatment failure can occur following an appropriate 12-week course of a pan-genotypic regimen. Here we describe four kidney transplant recipients of organs from donors with HCV infection (three with genotype 3, one genotype 1a) in whom first-line DAA treatment with either glecaprevir-pibrenatasvir or sofosbuvir-velpatasvir was unsuccessful, started 22-35 days after the day of transplantation. All ultimately achieved sustained virologic response with second- or third- line therapy. Post-treatment resistance associated substitutions were tested and noted to be present in two cases. Additionally, antiviral levels were assessed in two cases and found to be therapeutic in each. This article explores possible reasons for treatment failure, including medication interactions, bariatric surgery, viral dynamics, and drug resistance.