Detecting human cytomegalovirus drug resistant mutations and monitoring the emergence of resistant strains using real-time PCR

Volfová, Pavlína; Lengerová, Martina; Lochmanová, Jana; Dvořáková, Dana; Říčná, Dita; Palacková, Martina; Weinbergerová, Barbora; Mayer, Jiřı́; Ráčil, Zdeněk

doi:10.1016/j.jcv.2014.07.008

Cited by 10 publications

(4 citation statements)

References 12 publications

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“…Drug-resistant CMV infections caused by the human CMV phosphotransferase gene (UL97) and/or the polymerase gene (UL54) mutation were observed in 2-4% of patients with CMV reactivation after allo-HSCT, and always with severe outcomes [25][26][27][28]. Performing analyses of UL97 and UL54 in refractory CMV infection might identify further drug-resistant CMV infections.…”

Section: Discussionmentioning

confidence: 99%

Patients with refractory cytomegalovirus (CMV) infection following allogeneic haematopoietic stem cell transplantation are at high risk for CMV disease and non-relapse mortality

Liu

Kong

Chang

et al. 2015

Clinical Microbiology and Infection

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Pre-emptive therapy is an effective approach for cytomegalovirus (CMV) control; however, refractory CMV still occurs in a considerable group of recipients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Until now, hardly any data have been available about the clinical characteristics and risk factors of refractory CMV, or its potential harmful impact on the clinical outcome following allo-HSCT. We studied transplant factors affecting refractory CMV in the 100 days after allo-HSCT, and the impact of refractory CMV on the risk of CMV disease and non-relapse mortality (NRM). We retrospectively studied 488 consecutive patients with CMV infection after allo-HSCT. Patients with refractory CMV in the 100 days after allo-HSCT had a higher incidence of CMV disease and NRM than those without refractory CMV (11.9% vs. 0.8% and 17.1% vs. 8.3%, respectively). Multivariate analysis showed that refractory CMV infection in the 100 days after allo-HSCT was an independent risk factor for CMV disease (hazard ratio (HR) 10.539, 95% CI 2.467-45.015, p 0.001), and that refractory CMV infection within 60-100 days after allo-HSCT was an independent risk factor for NRM (HR 8.435, 95% CI 1.511-47.099, p 0.015). Clinical factors impacting on the risk of refractory CMV infection included receiving transplants from human leukocyte antigen-mismatched family donors (HR 2.012, 95% CI 1.603-2.546, p <0.001) and acute graft-versus-host disease (HR 1.905, 95% CI 1.352-2.686, p <0.001). We conclude that patients with refractory CMV infection during the early stage after allo-HSCT are at high risk for both CMV disease and NRM.

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Section: Discussionmentioning

confidence: 99%

Patients with refractory cytomegalovirus (CMV) infection following allogeneic haematopoietic stem cell transplantation are at high risk for CMV disease and non-relapse mortality

Liu

Kong

Chang

et al. 2015

Clinical Microbiology and Infection

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“…However the clinical correlates of CMV positivity in saliva are unclear, whereas assays of the blood have established prognostic value [8]. PCR assays can also distinguish strains of CMV, including those resistant to ganciclovir used for therapy and prophylaxis [9,10]. In Australia, the 'gold standard' for CMV detection is the Abbot Molecular assay as it is highly sensitive and reliable.…”

Section: Clinical Significance Of Detecting CMV Dnamentioning

confidence: 99%

HIV patients, healthy aging and transplant recipients can reveal the hidden footprints of CMV

Waters

Brook

Lee

et al. 2018

Clinical Immunology

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Cytomegalovirus (CMV) is a β-herpesvirus. Latent infections are common in all populations. However age-associated increases in levels of CMV-reactive antibody are testament to repeated reactivations and periods of viral replication. CMV has been associated with several diseases of aging, including vasculopathy and neurocognitive impairment. These conditions occur at a younger age in persons with particularly high burdens of CMV - transplant recipients and people living with HIV. Here we define the "clinical footprints" as immunopathologies triggered by CMV that develop over many years. A high burden of CMV also drives accumulation of multifunctional terminally-differentiated αβ T-cells, a novel population of Vδ2 γδ T-cells, and a population of CD56 NK cells lacking a key regulatory molecule. An understanding of these "immunological footprints" of CMV may reveal how they collectively promote the "clinical footprints" of the virus. This is explored here in transplant recipients, HIV patients and healthy aging.

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“…The majority of drug resistance mutations have been reported in immunocompromised hosts, especially in SOT and AIDS patients with very few data on HSCT patients . Overall, in HSCT recipients, HCMV resistance remains relatively rare, ranging from 1.7% to 5.1% .…”

Section: Human Cytomegalovirus Drug Resistancementioning

confidence: 99%

Human cytomegalovirus antiviral drug resistance in hematopoietic stem cell transplantation: current state of the art

Campos

Ribeiro

Boutolleau

et al. 2016

Reviews in Medical Virology

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Human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant recipients. The significant clinical impact of HCMV infection and progression to HCMV disease among allogeneic hematopoietic stem cell transplant recipients has been reduced by prophylactic, preemptive, and curative treatments using ganciclovir, valganciclovir, foscarnet, and cidofovir. Resistance to (val)ganciclovir results from mutations localized in HCMV UL97 gene (encoding the pUL97 phosphotransferase), UL54 gene (encoding the pUL54 DNA polymerase), or both genes, whereas foscarnet and cidofovir resistance results from mutations localized within UL54 gene only. This review is focused on HCMV antiviral drug resistance, including the functions of target genes of antivirals, the mechanisms of antiviral resistance, the different mutations in pUL97 and pUL54 that have been identified in either clinical isolates or laboratory strains, and their impact on HCMV susceptibility to antiviral drugs. It emphasizes the importance of proving that observed genetic changes confer resistance so they can be distinguished from polymorphisms. Because of the emergence of HCMV resistance to currently available drugs, novel drugs are urgently needed for the therapeutic management of HCMV-resistant infections in hematopoietic stem cell transplant patients.

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Detecting human cytomegalovirus drug resistant mutations and monitoring the emergence of resistant strains using real-time PCR

Cited by 10 publications

References 12 publications

Patients with refractory cytomegalovirus (CMV) infection following allogeneic haematopoietic stem cell transplantation are at high risk for CMV disease and non-relapse mortality

Patients with refractory cytomegalovirus (CMV) infection following allogeneic haematopoietic stem cell transplantation are at high risk for CMV disease and non-relapse mortality

HIV patients, healthy aging and transplant recipients can reveal the hidden footprints of CMV

Human cytomegalovirus antiviral drug resistance in hematopoietic stem cell transplantation: current state of the art

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