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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish
Pages (from-to)536-539
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume53
Issue number3
DOIs
Publication statusPublished - Mar 2004

Fingerprint

Cytomegalovirus
Tissue Donors
Transplants
Lung
Ganciclovir
Cytomegalovirus Infections
Immunity
Foscarnet
Mutation
Viremia
Pharmaceutical Preparations
Genes
Flow Cytometry
Cytokines
Viruses
Kidney
Therapeutics

Keywords

  • CD4 cell response
  • DR
  • Drug resistance
  • HCMV

ASJC Scopus subject areas

  • Microbiology
  • Pharmacology

Cite this

@article{aceb162ef019492baa71333c5f09ccad,
title = "Human cytomegalovirus double resistance in a donor-positve/recipient-negative lung transplant patient with an impaired CD4-mediated specific immune response",
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.",
keywords = "CD4 cell response, DR, Drug resistance, HCMV",
author = "Fausto Baldanti and Daniele Lilleri and Giulia Campanini and Giuditta Comolli and Ridolfo, {Anna Lisa} and Stefano Rusconi and Giuseppe Gerna",
year = "2004",
month = "3",
doi = "10.1093/jac/dkh065",
language = "English",
volume = "53",
pages = "536--539",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Human cytomegalovirus double resistance in a donor-positve/recipient-negative lung transplant patient with an impaired CD4-mediated specific immune response

AU - Baldanti, Fausto

AU - Lilleri, Daniele

AU - Campanini, Giulia

AU - Comolli, Giuditta

AU - Ridolfo, Anna Lisa

AU - Rusconi, Stefano

AU - Gerna, Giuseppe

PY - 2004/3

Y1 - 2004/3

N2 - 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.

AB - 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.

KW - CD4 cell response

KW - DR

KW - Drug resistance

KW - HCMV

UR - http://www.scopus.com/inward/record.url?scp=1642330769&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642330769&partnerID=8YFLogxK

U2 - 10.1093/jac/dkh065

DO - 10.1093/jac/dkh065

M3 - Article

C2 - 14739146

AN - SCOPUS:1642330769

VL - 53

SP - 536

EP - 539

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 3

ER -