The current coronavirus disease 2019 (COVID-19) pandemic requires extra attention for immunocompromised patients, including solid organ transplant recipients. We report on a case of a 35-year-old... Show moreThe current coronavirus disease 2019 (COVID-19) pandemic requires extra attention for immunocompromised patients, including solid organ transplant recipients. We report on a case of a 35-year-old renal transplant recipient who suffered from a severe COVID-19 pneumonia. The clinical course was complicated by extreme overexposure to the mammalian target of rapamycin inhibitor everolimus, following coadministration of chloroquine and lopinavir/ritonavir therapy. The case is illustrative for dilemmas that transplant professionals may face in the absence of evidence-based COVID-19 therapy and concurrent pressure for exploration of experimental pharmacological treatment options. However, the risk-benefit balance of experimental or off-label therapy may be weighed differently in organ transplant recipients than in otherwise healthy COVID-19 patients, owing to their immunocompromised status and potential drug interactions with immunosuppressive therapy. With this case report, we aimed to achieve increased awareness and improved management of drug-drug interactions associated with the various treatment options for COVID-19 in renal transplant patients. Show less
Abacavir administration is associated with drug-induced hypersensitivity reactions in HIV+ individuals expressing the HLA-B*57:01 allele. However, the immunological effects of abacavir... Show moreAbacavir administration is associated with drug-induced hypersensitivity reactions in HIV+ individuals expressing the HLA-B*57:01 allele. However, the immunological effects of abacavir administration in an HLA-B57 mismatched transplantation setting have not been studied. We hypothesized that abacavir exposure could induce de novo HLA-B57-specific allorecognition. HIV-specific CD8 T cell clones were generated from HIV+ individuals, using single cell sorting based on HIV peptide/HLA tetramer staining. The T cell clones were assayed for alloreactivity against a panel of single HLA-expressing cell lines, in the presence or absence of abacavir. Cytokine assay, CD137 upregulation, and cytotoxicity were used as readout. Abacavir exposure can induce de novo HLA-B57 allorecognition by HIV-specific T cells. A HIV Gag RK9/HLA-A3-specific T cell did exhibit interferon-gamma production, CD137 upregulation, and cytolytic effector function against allogeneic HLA-B57, but only in the presence of abacavir. Allorecognition was specific to the virus specificity, HLA restriction, and T cell receptor TRBV use of the T cell. We provide proof-of-principle evidence that administration of a drug could induce specific allorecognition of mismatched HLA molecules in the transplant setting. We suggest that HIV-seropositive recipients of an HLA-B57 mismatched graft should not receive abacavir until further studies are completed. Show less
