Abstract
Background: Emergence of human cytomegalovirus (HCMV) resistance to ganciclovir in solid-organ transplant recipients has been found to be mostly associated with primary HCMV infection. Materials and methods: The case of a donor-positive/recipeent-negative (D+/R-) lung transplant patient developing ganciclovir and cidofovir resistance is described. HCMV infection was monitored by weekly determination of antigenaemia, viraemia and DNAaemia. HCMV-specific CD4 cell immunity was determined by cytokine flow cytometry. The emergence of drug-resistant HCMV strains was documented by sequencing of UL97 and UL54 genes of HCMV directly in blood samples. Results: Following primary HCMV infection, the patient showed repeated reactivations for over a year, eventually resulting in the selection of a ganciclovir-resistant HCMV strain with a mutation in the UL97 gene product (A594V). Determination of HCMV-specific CD4 cell immunity showed a persistently impaired immune response. Subsequent foscarnet treatment allowed only transitory virus clearance from blood owing to renal toxicity. Further ganciclovir treatment induced a new mutation in both UL97 (H520Q) and UL54 (P522S) with final emergence of double resistance to both ganciclovir and cidofovir. The patient eventually died of lung failure. Discussion: Determination of HCMV-specific CD4 cell immunity could be of help in predicting the emergence of drug-resistant strains in D+/R-transplant recipients.
Original language | English |
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Pages (from-to) | 536-539 |
Number of pages | 4 |
Journal | Journal of Antimicrobial Chemotherapy |
Volume | 53 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 2004 |
Keywords
- CD4 cell response
- DR
- Drug resistance
- HCMV
ASJC Scopus subject areas
- Microbiology
- Pharmacology