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Master Thesis

Caractéristiques et analyse chronologique des infections à CMV conduisant à une résistance aux antiviraux, étude rétrospective mono-centrique du CHU de Bordeaux

Abstract : Introduction: CMV guidelines recommend testing for an antiviral drug resistance in kidney transplant recipients (KTR) who exhibit the two following criteria: 1/ a cumulative (Val)ganciclovir ((V)GCV) exposure >6 weeks and 2/ a treatment failure after >2 weeks of ongoing full dose (V)GCV. The objectives of this study were to describe the characteristics, the risk factors and the time course of CMV infections leading to antiviral drug resistance. Material and methods: we performed a retrospective cohort study in 313 KTR treated for a first episode of CMV infection or disease from Oct 2004 to December 2017. Logistic and Cox regression analyses were performed for identifying risk factors of persistent CMV DNAemia, CMV recurrence, and antiviral drug resistance. Results: fifty-eight (18%) of the 313 KTR developed persistent CMV DNAemia and 65 (21%) clinical recurrence. The risk factors of persistent CMV DNAemia and clinical recurrence were similar: treatment with corticosteroid and anti-lymphocyte globulin, D+R- CMV serostatus, lymphopenia, high viral load and CMV disease. The incidence of an antiviral drug resistance was 6.3% (20/313). Importantly, 30% of antiviral drug resistances were detected outside the screening criteria indicated by the guidelines. We found that persistent CMV DNAemia (HR = 6.25, CI95% 2.45-15.96, p <0.001) and clinical recurrence (HR = 7.20, CI95% 2.57-18.09, p <0.001) were the only risk factors associated with the development of antiviral drug resistance. The addition of the clinical recurrence to the 2 current criteria improved the screening strategy of antiviral drug resistance by 10%. Conclusion: we identified a new scenario leading to resistance to antivirals associating persistent CMV DNAemia and clinical recurrence. This perspective involving a chronological analysis of the history of the CMV episode could allow a better and earlier diagnosis of antiviral resistance.
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https://dumas.ccsd.cnrs.fr/dumas-02985999
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Submitted on : Monday, November 2, 2020 - 4:01:10 PM
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Mathieu Acquier. Caractéristiques et analyse chronologique des infections à CMV conduisant à une résistance aux antiviraux, étude rétrospective mono-centrique du CHU de Bordeaux. Sciences du Vivant [q-bio]. 2020. ⟨dumas-02985999⟩

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