ABSTRACT
BACKGROUND: Nirmatrelvir/ritonavir, a newly authorized drug for the treatment of COVID-19, is a strong CYP3A4 inhibitor that can interact with many drugs, such as tacrolimus, reducing its metabolism. The reported case is a renal transplant patient who experienced a strong increase in tacrolimus blood concentration (up to 112ng/mL, more than ten times above the target range) when treated with both drugs at the same time, which caused a neurologic condition that required hospital admission for its control and treatment. The resolution of the symptoms was rapid, but the elevation of tacrolimus concentration remained for several days, even after discontinuing both drugs. This case shows the importance of developing a protocol for managing this interaction to guarantee the efficacy and safety of treatment with nirmatrelvir/ritonavir in transplant patients.
ABSTRACT
Nirmatrelvir/ritonavir, a newly authorized drug for the treatment of COVID-19, is a strong CYP3A4 inhibitor, which can interact with a large number of drugs, such as tacrolimus, reducing its metabolism. The reported case is a renal transplant patient who experienced a strong increase in tacrolimus blood concentration (up to 112ng/ml, more than ten times the reference range) when treated with both drugs at the same time, which caused a neurological condition that required hospital admission its control and treatment. The resolution of the symptoms was rapid, but the elevation of tacrolimus concentration remained for several days, even after discontinuation of both drugs. This study shows the importance of developing a protocol for the management of this interaction to guarantee the efficacy and safety of treatment with nirmatrelvir/ritonavir in transplant patients.
Subject(s)
COVID-19ABSTRACT
Global pandemics by influenza or coronaviruses cause severe disruptions to the public health and lead to severe morbidity and mortality. Vaccines against these pathogens remain a medical need. CMV (cytomegalovirus) is a β-herpesvirus that induces uniquely robust immune responses, where outstandingly large populations of antigen-specific CD8+ T cells are maintained for a lifetime. Hence, CMV has been proposed and investigated as a novel vaccine vector expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens. We generated two recombinant murine CMV (MCMV) vaccine vectors expressing the hemagglutinin (HA) of influenza A virus (MCMVHA) or the spike protein of the severe acute respiratory syndrome coronavirus 2 (MCMVS). A single shot of MCMVs expressing either viral protein induced potent neutralizing antibody responses, which strengthened over time. Importantly, MCMVHA vaccinated mice were protected from illness following challenge with the influenza virus, and we excluded that this protection was due to effects of memory T cells. Conclusively, we show here that MCMV vectors do not only induce long-term cellular immunity, but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.