Dataset Information

Molecular detection and genotyping of Human Cytomegalovirus in kidney transplant recipients under ganciclovir prophylaxis in Iran.

ABSTRACT:

Introduction

Human Cytomegalovirus (HCMV) infection is one of the most common viral complications in kidney transplant recipients. Although there are effective treatments strategies for the HCMV infection, this infection is still one of the causes of kidney transplant rejection.

Methods

A total of 246 kidney transplant recipients participated in this cross-sectional study. Viral DNA was extracted from these plasma samples and the presence of HCMV genome was determined by Semi-nested PCR with specific primers for HCMV B glycoprotein gene. Sanger sequencing analyses were carried out to determine HCMV genotypes and Mega x software was used for nucleotide alignment and construction of a phylogenetic tree.

Results

Human cytomegalovirus DNA was detected in 11 (4.47%) recipients. According to the phylogenetic analysis, HCMV gB3 was 50% among kidney transplant recipients, followed by gB4 30% and gB1 20% however, the gB2 genotype was not detected.

Conclusions

This study demonstrated that the HCMV infection in our patients is relatively low because all transplant recipients received appropriate prophylaxis, thereby antiviral prophylaxis is recommended for all patients at risk of HCMV infection after kidney transplantation. Also, gB3 was the most predominant genotype among our kidney transplant recipients that was related to the higher rate of prevalence of severe HCMV infections. Moreover, elevated serum creatinine level was detected in patients at the time of detection of HCMV infection.

SUBMITTER: Behnezhad F

PROVIDER: S-EPMC10015764 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Molecular Detection and Genotyping of Human Cytomegalovirus in Kidney Transplant Recipients under Ganciclovir Prophylaxis in Iran.

Behnezhad Farzane F Parhizgari Najmeh N Shafiei-Jandaghi Nazanin Zahra NZ Yavarian Jila J Mokhtari-Azad Talat T

Intervirology 20220720 1

<h4>Introduction</h4>Human cytomegalovirus (HCMV) infection is one of the most common viral complications in kidney transplant recipients. Although there are effective treatments strategies for the HCMV infection, this infection is still one of the causes of kidney transplant rejection.<h4>Methods</h4>A total of 246 kidney transplant recipients participated in this cross-sectional study. Viral DNA was extracted from these plasma samples, and the presence of HCMV genome was determined by semi-nes ...[more]

PMID: 35858540

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Project description:Cytomegalovirus infection during antiviral prophylaxis occurs in transplant recipients despite individualized regimens based on renal function. Fifty kidney transplant recipients were assessed between 2016 and 2019 for valganciclovir dosing, ganciclovir exposure, cytomegalovirus infection, and genotypic resistance markers during the first year posttransplant. Ganciclovir plasma concentrations were measured using mass spectrometry. Population pharmacokinetics was used to determine individual ganciclovir exposure and to evaluate the ability of manufacturer dosing guidelines to meet therapeutic target daily area under the curve (AUC24) of 40 to 50 μg·h/mL. Full-length UL54 and UL97 were assessed using high-throughput sequencing in cytomegalovirus DNA-positive patient specimens. Valganciclovir doses administered to recipients with creatinine clearance of <40 mL/min were higher than specified by guidelines, and they were lower for recipients with creatinine clearance of ≥40 mL/min. The mean ganciclovir AUC24 was 33 ± 13 μg·h/mL, and 82% of subjects did not attain the therapeutic target. Pharmacokinetic simulations showed that the guidelines similarly could not attain the therapeutic target in 79% of individuals. Cytomegalovirus breakthrough occurred in 6% (3/50) of recipients, while 12% (6/50) developed late-onset infection. The mean AUC24s of recipients with (n = 3) and without (n = 47) infection were not significantly different (P = 0.528). However, one recipient with an AUC24 of 20 μg·h/mL acquired two UL97 ganciclovir resistance mutations. Current prophylaxis guidelines resulted in subtherapeutic ganciclovir exposure in several study recipients, including the emergence of resistance genotypes. IMPORTANCE This study examined the pharmacokinetics and viral genomic data from a prospective cohort of kidney transplant recipients undergoing valganciclovir prophylaxis for cytomegalovirus (CMV) prevention. We showed for the first time using high-throughput sequencing the detection of ganciclovir resistance mutations in breakthrough CMV infection during subtherapeutic plasma ganciclovir as indicated by the pharmacokinetic parameter daily area under the curve (AUC24). In addition, we found that current valganciclovir dosing guidelines for CMV prophylaxis are predicted to attain therapeutic targets in only 21% of recipients, which is consistent with previous pharmacokinetic studies. The novel findings of resistance mutations during subtherapeutic ganciclovir exposure presented here can inform future studies investigating the dynamics of drug selection pressure and the emergence of resistance mutations in vivo.

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