Phenotype and Genotype Study of Novel C480F Maribavir-Ganciclovir Cross-Resistance Mutation Detected in Hematopoietic Stem Cell and Solid Organ Transplant Recipients
Abstract Two transplant recipients (1 kidney and 1 hematopoietic stem cell) received maribavir (MBV) after cytomegalovirus (CMV) infection clinically resistant to standard therapy. Both patients achieved CMV DNA clearance within 30 and 18 days; however, the UL97 C480F variant emerged, causing recurr...
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| Veröffentlicht in: | The Journal of infectious diseases 2021-09, Vol.224 (6), p.1024-1028 |
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| creator | Santos Bravo, Marta Plault, Nicolas Sánchez Palomino, Sonsoles Mosquera Gutierrez, María Mar Fernández Avilés, Francesc Suarez Lledo, María Sabé Fernández, Nuria Rovira, Montserrat Alain, Sophie Marcos Maeso, M Ángeles |
| description | Abstract
Two transplant recipients (1 kidney and 1 hematopoietic stem cell) received maribavir (MBV) after cytomegalovirus (CMV) infection clinically resistant to standard therapy. Both patients achieved CMV DNA clearance within 30 and 18 days; however, the UL97 C480F variant emerged, causing recurrent CMV infection after a cumulative 2 months of MBV and 15 or 4 weeks of ganciclovir treatment, respectively. C480F was not detected under ganciclovir before MBV treatment. Recombinant phenotyping showed that C480F conferred the highest level of MBV resistance and ganciclovir cross-resistance, with impaired viral growth. Clinical follow-up and genotypic and phenotypic studies are essential for the assessment and optimization of patients with suspected MBV resistance.
A cytomegalovirus UL97 C480F mutation emerged after maribavir treatment in 2 transplant recipients (1 kidney, 1 hematopoietic stem cell). Phenotypic assay confirmed that C480F confers a high level of maribavir resistance and ganciclovir cross-resistance, with a decreased replicative capacity. |
| doi_str_mv | 10.1093/infdis/jiab029 |
| format | Article |
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Two transplant recipients (1 kidney and 1 hematopoietic stem cell) received maribavir (MBV) after cytomegalovirus (CMV) infection clinically resistant to standard therapy. Both patients achieved CMV DNA clearance within 30 and 18 days; however, the UL97 C480F variant emerged, causing recurrent CMV infection after a cumulative 2 months of MBV and 15 or 4 weeks of ganciclovir treatment, respectively. C480F was not detected under ganciclovir before MBV treatment. Recombinant phenotyping showed that C480F conferred the highest level of MBV resistance and ganciclovir cross-resistance, with impaired viral growth. Clinical follow-up and genotypic and phenotypic studies are essential for the assessment and optimization of patients with suspected MBV resistance.
A cytomegalovirus UL97 C480F mutation emerged after maribavir treatment in 2 transplant recipients (1 kidney, 1 hematopoietic stem cell). Phenotypic assay confirmed that C480F confers a high level of maribavir resistance and ganciclovir cross-resistance, with a decreased replicative capacity.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiab029</identifier><identifier>PMID: 33475730</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adult ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; Antiviral drugs ; Benzimidazoles - pharmacology ; Benzimidazoles - therapeutic use ; Cross-resistance ; Cytomegalovirus ; Cytomegalovirus - drug effects ; Cytomegalovirus - genetics ; Cytomegalovirus Infections - drug therapy ; Drug Resistance, Viral - drug effects ; Drug Resistance, Viral - genetics ; Female ; Ganciclovir ; Ganciclovir - pharmacology ; Ganciclovir - therapeutic use ; Genotypes ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hematopoietic Stem Cells ; Humans ; Kidney Transplantation - adverse effects ; Kidney transplants ; Mutation - drug effects ; Organ Transplantation ; Patients ; Phenotypes ; Phenotyping ; Phosphotransferases (Alcohol Group Acceptor) - genetics ; Phosphotransferases (Alcohol Group Acceptor) - therapeutic use ; Recurrent infection ; Ribonucleosides - pharmacology ; Ribonucleosides - therapeutic use ; Stem cell transplantation ; Stem cells ; Transplant Recipients ; Treatment Outcome</subject><ispartof>The Journal of infectious diseases, 2021-09, Vol.224 (6), p.1024-1028</ispartof><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c397t-a675360bd46485c2c0191344617c7e93653cea7a7401c6410a2c6e04ae23e7f03</citedby><cites>FETCH-LOGICAL-c397t-a675360bd46485c2c0191344617c7e93653cea7a7401c6410a2c6e04ae23e7f03</cites><orcidid>0000-0001-5270-4454 ; 0000-0002-9787-1421</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33475730$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Santos Bravo, Marta</creatorcontrib><creatorcontrib>Plault, Nicolas</creatorcontrib><creatorcontrib>Sánchez Palomino, Sonsoles</creatorcontrib><creatorcontrib>Mosquera Gutierrez, María Mar</creatorcontrib><creatorcontrib>Fernández Avilés, Francesc</creatorcontrib><creatorcontrib>Suarez Lledo, María</creatorcontrib><creatorcontrib>Sabé Fernández, Nuria</creatorcontrib><creatorcontrib>Rovira, Montserrat</creatorcontrib><creatorcontrib>Alain, Sophie</creatorcontrib><creatorcontrib>Marcos Maeso, M Ángeles</creatorcontrib><title>Phenotype and Genotype Study of Novel C480F Maribavir-Ganciclovir Cross-Resistance Mutation Detected in Hematopoietic Stem Cell and Solid Organ Transplant Recipients</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Abstract
Two transplant recipients (1 kidney and 1 hematopoietic stem cell) received maribavir (MBV) after cytomegalovirus (CMV) infection clinically resistant to standard therapy. Both patients achieved CMV DNA clearance within 30 and 18 days; however, the UL97 C480F variant emerged, causing recurrent CMV infection after a cumulative 2 months of MBV and 15 or 4 weeks of ganciclovir treatment, respectively. C480F was not detected under ganciclovir before MBV treatment. Recombinant phenotyping showed that C480F conferred the highest level of MBV resistance and ganciclovir cross-resistance, with impaired viral growth. Clinical follow-up and genotypic and phenotypic studies are essential for the assessment and optimization of patients with suspected MBV resistance.
A cytomegalovirus UL97 C480F mutation emerged after maribavir treatment in 2 transplant recipients (1 kidney, 1 hematopoietic stem cell). Phenotypic assay confirmed that C480F confers a high level of maribavir resistance and ganciclovir cross-resistance, with a decreased replicative capacity.</description><subject>Adult</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Antiviral drugs</subject><subject>Benzimidazoles - pharmacology</subject><subject>Benzimidazoles - therapeutic use</subject><subject>Cross-resistance</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus - drug effects</subject><subject>Cytomegalovirus - genetics</subject><subject>Cytomegalovirus Infections - drug therapy</subject><subject>Drug Resistance, Viral - drug effects</subject><subject>Drug Resistance, Viral - genetics</subject><subject>Female</subject><subject>Ganciclovir</subject><subject>Ganciclovir - pharmacology</subject><subject>Ganciclovir - therapeutic use</subject><subject>Genotypes</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hematopoietic Stem Cells</subject><subject>Humans</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Kidney transplants</subject><subject>Mutation - drug effects</subject><subject>Organ Transplantation</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>Phenotyping</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - genetics</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - therapeutic use</subject><subject>Recurrent infection</subject><subject>Ribonucleosides - pharmacology</subject><subject>Ribonucleosides - therapeutic use</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Transplant Recipients</subject><subject>Treatment Outcome</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1ERbelV47IEhc4pPVX7PURBbpFainqxznyOhPwKrGD7VTaH8T_rMtue-DCaT70zDujeRF6R8kpJZqfOd93Lp1tnFkTpl-hBa25qqSk_DVaEMJYRZdaH6KjlDaEEMGleoMOOReqVpws0J8fv8CHvJ0AG9_h1XNxm-dui0OPv4cHGHAjluQcX5no1ubBxWplvHV2CCXHTQwpVTeQXMqlDfhqzia74PEXyGAzdNh5fAGjyWEKDrKzRR5G3MAw_N16GwbX4ev403h8F41P02B8xjdg3eTA5_QWHfRmSHCyj8fo_vzrXXNRXV6vvjWfLyvLtcqVkarmkqw7IcWytswSqikXQlJlFWgua27BKKMEoVYKSgyzEogwwDionvBj9HGnO8Xwe4aU29ElW840HsKcWiaUVpQoJgr64R90E-boy3Utq5WUaqklK9TpjrJPT4rQt1N0o4nblpL2ycB2Z2C7N7AMvN_LzusRuhf82bECfNoBYZ7-J_YIGTKnyg</recordid><startdate>20210917</startdate><enddate>20210917</enddate><creator>Santos Bravo, Marta</creator><creator>Plault, Nicolas</creator><creator>Sánchez Palomino, Sonsoles</creator><creator>Mosquera Gutierrez, María Mar</creator><creator>Fernández Avilés, Francesc</creator><creator>Suarez Lledo, María</creator><creator>Sabé Fernández, Nuria</creator><creator>Rovira, Montserrat</creator><creator>Alain, Sophie</creator><creator>Marcos Maeso, M Ángeles</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5270-4454</orcidid><orcidid>https://orcid.org/0000-0002-9787-1421</orcidid></search><sort><creationdate>20210917</creationdate><title>Phenotype and Genotype Study of Novel C480F Maribavir-Ganciclovir Cross-Resistance Mutation Detected in Hematopoietic Stem Cell and Solid Organ Transplant Recipients</title><author>Santos Bravo, Marta ; Plault, Nicolas ; Sánchez Palomino, Sonsoles ; Mosquera Gutierrez, María Mar ; Fernández Avilés, Francesc ; Suarez Lledo, María ; Sabé Fernández, Nuria ; Rovira, Montserrat ; Alain, Sophie ; Marcos Maeso, M Ángeles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c397t-a675360bd46485c2c0191344617c7e93653cea7a7401c6410a2c6e04ae23e7f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Antiviral Agents - pharmacology</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Antiviral drugs</topic><topic>Benzimidazoles - pharmacology</topic><topic>Benzimidazoles - therapeutic use</topic><topic>Cross-resistance</topic><topic>Cytomegalovirus</topic><topic>Cytomegalovirus - drug effects</topic><topic>Cytomegalovirus - genetics</topic><topic>Cytomegalovirus Infections - drug therapy</topic><topic>Drug Resistance, Viral - drug effects</topic><topic>Drug Resistance, Viral - genetics</topic><topic>Female</topic><topic>Ganciclovir</topic><topic>Ganciclovir - pharmacology</topic><topic>Ganciclovir - therapeutic use</topic><topic>Genotypes</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Hematopoietic Stem Cells</topic><topic>Humans</topic><topic>Kidney Transplantation - adverse effects</topic><topic>Kidney transplants</topic><topic>Mutation - drug effects</topic><topic>Organ Transplantation</topic><topic>Patients</topic><topic>Phenotypes</topic><topic>Phenotyping</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - genetics</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - therapeutic use</topic><topic>Recurrent infection</topic><topic>Ribonucleosides - pharmacology</topic><topic>Ribonucleosides - therapeutic use</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Transplant Recipients</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Santos Bravo, Marta</creatorcontrib><creatorcontrib>Plault, Nicolas</creatorcontrib><creatorcontrib>Sánchez Palomino, Sonsoles</creatorcontrib><creatorcontrib>Mosquera Gutierrez, María Mar</creatorcontrib><creatorcontrib>Fernández Avilés, Francesc</creatorcontrib><creatorcontrib>Suarez Lledo, María</creatorcontrib><creatorcontrib>Sabé Fernández, Nuria</creatorcontrib><creatorcontrib>Rovira, Montserrat</creatorcontrib><creatorcontrib>Alain, Sophie</creatorcontrib><creatorcontrib>Marcos Maeso, M Ángeles</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Santos Bravo, Marta</au><au>Plault, Nicolas</au><au>Sánchez Palomino, Sonsoles</au><au>Mosquera Gutierrez, María Mar</au><au>Fernández Avilés, Francesc</au><au>Suarez Lledo, María</au><au>Sabé Fernández, Nuria</au><au>Rovira, Montserrat</au><au>Alain, Sophie</au><au>Marcos Maeso, M Ángeles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phenotype and Genotype Study of Novel C480F Maribavir-Ganciclovir Cross-Resistance Mutation Detected in Hematopoietic Stem Cell and Solid Organ Transplant Recipients</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2021-09-17</date><risdate>2021</risdate><volume>224</volume><issue>6</issue><spage>1024</spage><epage>1028</epage><pages>1024-1028</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><abstract>Abstract
Two transplant recipients (1 kidney and 1 hematopoietic stem cell) received maribavir (MBV) after cytomegalovirus (CMV) infection clinically resistant to standard therapy. Both patients achieved CMV DNA clearance within 30 and 18 days; however, the UL97 C480F variant emerged, causing recurrent CMV infection after a cumulative 2 months of MBV and 15 or 4 weeks of ganciclovir treatment, respectively. C480F was not detected under ganciclovir before MBV treatment. Recombinant phenotyping showed that C480F conferred the highest level of MBV resistance and ganciclovir cross-resistance, with impaired viral growth. Clinical follow-up and genotypic and phenotypic studies are essential for the assessment and optimization of patients with suspected MBV resistance.
A cytomegalovirus UL97 C480F mutation emerged after maribavir treatment in 2 transplant recipients (1 kidney, 1 hematopoietic stem cell). Phenotypic assay confirmed that C480F confers a high level of maribavir resistance and ganciclovir cross-resistance, with a decreased replicative capacity.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>33475730</pmid><doi>10.1093/infdis/jiab029</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-5270-4454</orcidid><orcidid>https://orcid.org/0000-0002-9787-1421</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Antiviral drugs Benzimidazoles - pharmacology Benzimidazoles - therapeutic use Cross-resistance Cytomegalovirus Cytomegalovirus - drug effects Cytomegalovirus - genetics Cytomegalovirus Infections - drug therapy Drug Resistance, Viral - drug effects Drug Resistance, Viral - genetics Female Ganciclovir Ganciclovir - pharmacology Ganciclovir - therapeutic use Genotypes Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic Stem Cells Humans Kidney Transplantation - adverse effects Kidney transplants Mutation - drug effects Organ Transplantation Patients Phenotypes Phenotyping Phosphotransferases (Alcohol Group Acceptor) - genetics Phosphotransferases (Alcohol Group Acceptor) - therapeutic use Recurrent infection Ribonucleosides - pharmacology Ribonucleosides - therapeutic use Stem cell transplantation Stem cells Transplant Recipients Treatment Outcome |
| title | Phenotype and Genotype Study of Novel C480F Maribavir-Ganciclovir Cross-Resistance Mutation Detected in Hematopoietic Stem Cell and Solid Organ Transplant Recipients |
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