Journal Article

Human cytomegalovirus double resistance in a donor-positive/recipient-negative lung transplant patient with an impaired CD4-mediated specific immune response

Fausto Baldanti, Daniele Lilleri, Giulia Campanini, Giuditta Comolli, Anna Lisa Ridolfo, Stefano Rusconi and Giuseppe Gerna

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 53, issue 3, pages 536-539
Published in print March 2004 | ISSN: 0305-7453
Published online March 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh065
Human cytomegalovirus double resistance in a donor-positive/recipient-negative lung transplant patient with an impaired  CD4-mediated specific immune response

Show Summary Details

Preview

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/recipient-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.

Keywords: Keywords: HCMV, drug resistance, D+R–, CD4 cell response

Journal Article.  2162 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.