Maribavir is indicated for the treatment of refractory cytomegalovirus (CMV) infection/disease in patients who have undergone a solid organ transplant (SOT) or hematopoietic cell transplant (HCT). Only limited data on its use in real-world settings have been published from retrospective series. This retrospective study describes the real-world effectiveness of maribavir in 79 transplant patients with refractory CMV infection (67 SOT and 12 HCT) treated under a compassionate use program in France between October 2021 and April 2023. Maribavir was administered for <8 weeks, 8 weeks, and >8 weeks in 17, 32, and 30 patients, respectively. The response rate, defined as viremia clearance, was 53.2%, with a median time to first CMV clearance of 59 days. CMV clearance was observed in patients beyond 8 weeks of treatment. De novo maribavir resistance mutations were observed in 13.9% of patients, and CMV recurrence occurred in 45.2% of patients. Presence of CMV disease at baseline was associated with a lower likelihood of maribavir response. Compared to the pivotal SOLSTICE trial, real-world maribavir use demonstrated comparable effectiveness and a lower emergence of maribavir resistance. Moreover, outcomes of patients with a longer treatment duration suggested potential benefits of extending maribavir therapy beyond the recommended 8 weeks.

Résumé L’infection congénitale à cytomégalovirus est la première cause d’anomalies congénitales d’origine virale au niveau mondial touchant plus de 0,5 % des naissances. Après des années d’opposition de nos autorités de santé à la mise en place d’un dépistage de l’infection à cytomégalovirus (CMV) pendant la grossesse, l’analyse des dernières données sur l’efficacité du valaciclovir pour prévenir la transmission materno-foetale du CMV a conduit la Haute Autorité de santé (HAS) à proposer le 5 juin 2025 la mise en place d’un dépistage systématique de la primo-infection CMV lors du premier trimestre de grossesse, période la plus à risque d’atteintes foetales graves. Afin d’accompagner la mise en place de ce dépistage, le CNR Herpèsvirus et le LBMR Virus et périnatalité ont proposé des algorithmes d’interprétation des résultats et ont mené des campagnes d’information en association avec d’autres sociétés savantes telle que le collège national des gynécologues et obstétriciens français. Les laboratoires de biologie médicale se sont montrés très réactifs pour mettre en place ce dépistage et appliquer les recommandations, ce qui a généré une augmentation considérable de recours aux centres experts. Afin que le dépistage puisse gagner encore en performance, il serait pertinent d’identifier les difficultés rencontrées par les laboratoires à l’occasion de ce dépistage et leur apporter des réponses, de définir les trousses de sérologie CMV les plus efficaces à utiliser dans ce cadre et de renforcer le dialogue clinico-biologique avec un retour rapide des résultats au prescripteur. Une évaluation du dispositif est prévue à l’issu de trois années de déploiement.

Hepatitis delta (HDV) infection affects 5% of hepatitis B (HBV)-positive patients and is associated with an increased risk of cirrhosis and hepatocellular carcinoma; however, it remains underdiagnosed. The first part of our Delta Describe study highlights the insufficient level of HDV screening among patients in metropolitan France. In this study, we report on their real-world management. Patients with at least one positive HDV RNA test performed in 2019 were identified through the major public and private laboratories in France. From January 2024 to July 2025, informed patients were interviewed, and physicians supplemented the collected data. A total of 547 patients were included, with a median age of 44 years; most originated from Africa or Eastern Europe. HIV and hepatitis C coinfections were reported in 15.2% and 4.6% of patients, respectively. Liver fibrosis was primarily assessed using FibroScan®. Most patients knew the year of their delta diagnosis, and 69.1% knew their fibrosis stage. Liver-related events occurred in 14.3% (67/468) of patients, mainly comprising portal hypertension (61.6%), liver failure (12.3%), and hepatocellular carcinoma (26%), and 45 patients (45/468) underwent liver transplantation. At the time of the survey, 47.1% of the patients reported undetectable HDV RNA; 40.6% (222/547) had currently or previously undergone BLV treatment. Among patients receiving ongoing treatment for HDV at the time of the survey, 84.8% were receiving nucleos(t)ide analogs (NUCs). In metropolitan France, HDV patients had access to specialized follow-up care and innovative therapies (bulevirtide), were mostly on NUCs, and demonstrated good disease awareness.

The SCANVIR® project is a regional initiative aimed at accelerating the elimination of hepatitis C virus (HCV) by reaching high-risk populations outside traditional healthcare settings. Launched in 2017 in Limoges and later expanded to Poitiers and Bordeaux, the project organized dedicated screening and treatment days in 43 facilities taking care of intravenous drug users, migrants, and prisoners in Nouvelle-Aquitaine. These events involved multidisciplinary teams and advanced diagnostic tools, including rapid tests for HCV, HBV, and HIV; FibroScan® for liver assessment; and GeneXpert® for on-site HCV RNA detection. Patients also received counseling on risk prevention, addiction, psychosocial support, and treatment when needed. Between 2017 and 2024, SCANVIR® screened 1664 patients, with 98.9% accepting FibroScan®. Anti-HCV antibodies were detected in 23.4% of participants, among whom 41.5% (N = 162) had a replicative profile. Of these, 83% initiated treatment and 80% were cured or were still undergoing therapy. FibroScan® assessments showed advanced fibrosis in 17% of patients, severe fibrosis in 7.2%, and severe steatosis in 18%. By promoting a “Test, Treat, Prevent” strategy, SCANVIR® proved cost-effective in diagnosing and treating individuals distant from care structures, highlighting the value of integrating education and prevention into liver disease screening. SCANVIR® is an officially registered European trademark.

BACKGROUND:Maribavir is currently administered at a dose of 400 mg twice daily (q12h) for the treatment of cytomegalovirus (CMV) infections in transplant recipients. However, virological failure rates of up to 40% have been reported in clinical practice, with potentially severe consequences and the selection of mutant strains. OBJECTIVES:This study aims to evaluate, in silico, the pharmacokinetic (PK) and pharmacodynamic (PD) interest of alternative maribavir dosing regimens using population pharmacokinetic (POPPK) modelling and Monte Carlo simulations. METHODS:A published two-compartment POPPK model with first-order absorption and an absorption lag time was implemented. Monte Carlo simulations (n = 10 000 virtual PK profiles) were performed for maribavir regimens of 400, 600, and 800 mg administered q12h and every 8 h (q8h). PK metrics, including trough concentration (C0) and area under the concentration-time curve (AUC), as well as probability of target attainment (PTA), were compared across regimens at steady state. RESULTS:The standard 400 mg q12h regimen resulted in the lowest PTA, falling below 90% for a pharmacologically active inhibitory concentration 50 of 2 mg/L. In contrast, q8h regimens substantially improved PTA across targets and were associated with reduced interindividual variability in C0. CONCLUSIONS:Increasing dosing frequency to a three-times-daily regimen improved PK/PD target attainment compared with the standard q12h regimen. These findings support the need for prospective clinical and pharmacoeconomic studies to assess the benefit-risk balance of alternative maribavir dosing strategies.

Cytomegalovirus (CMV) infection poses significant challenges in solid organ transplant (SOT) recipients, impacting graft outcomes, morbidity, and in some cases survival. The ESOT CMV Workshop 2023 convened European experts to discuss current practices and advances in the management of CMV with the aim of improving the quality of life of transplant recipients. Discussions covered crucial areas such as preventive strategies, diagnostic challenges, therapeutic approaches, and the role of cell-mediated immunity (CMI) monitoring. Despite advances, ambiguity persists in optimal CMV management across European transplant centers. Preventive strategies, including universal prophylaxis and pre-emptive therapy, are effective but consensus is lacking with respect to the preferred approach. Diagnostic challenges such as standardization of viral load thresholds and detection of end-organ disease complicate timely intervention. While newer therapies like maribavir hold promise for treating complicated CMV infections, sustaining viral clearance remains a challenge. Integrating CMI monitoring into CMV management could personalize treatment decisions but has limitations in in terms of predictive value and accessibility. Further research is needed to fill these gaps and optimize CMV management. The collaborative efforts, led by the European Society for Organ Transplantation (ESOT), aim to standardize and improve CMV care, ensuring better outcomes for SOT recipients.

Cytomegalovirus (CMV) infections occur in 10%-40% of organ or stem cell transplant patients. Despite the low prevalence, CMV antiviral resistance has an important impact on patient outcomes. Guidelines for transplant recipients recommend that resistance should be suspected in cases of unchanged or increasing CMV viral loads after a minimum of 2 weeks of antiviral therapy at an appropriate dose or >6 weeks of ganciclovir exposure. Next-generation amplicon sequencing (NGS) makes it possible to directly target the genes involved in this resistance. Currently, six drugs are available, and six CMV genes (UL54-UL97-UL89-UL56-UL51-UL27 genes) can harbor mutations affecting drug efficacy. Here, we developed different primers targeting these six genes with long-range polymerase chain reaction (PCR). Based on clinical requirements, all genes or a subset could be sequenced in a single run using Oxford Nanopore technology and combined with an automatic bioinformatics pipeline to detect and report mutations. We utilized 46 blood samples, five external quality controls, and 10 mixes of two bacmids provided by the national reference center (CNR) Herpesvirus Limoges, each carrying distinct mutations. Assay performance (sensitivity, specificity, and accuracy) was evaluated through an interlaboratory exchange with CNR Herpesvirus. Long-range PCR combined with next-generation sequencing analysis enables earlier and more comprehensive discrimination of the double population and determines whether the detected single-nucleotide polymorphisms are present on single or multiple CMV strains. We developed a next-generation sequencing assay combined with eight long-range PCRs to sequence all genes involved in CMV antiviral resistance and to detect early low-frequency mutations.

Background/objectivesHuman papillomavirus (HPV) genotyping is essential for cervical cancer screening and prevention. The AllplexTM HPV28 real-time PCR kit, using different chemistry and results analysis compared with its predecessor, the AnyplexTM II HPV28 kit, has recently been launched. This study aims to compare the AllplexTM HPV28 and AnyplexTM II HPV28 assays in detecting and genotyping the 13 high-risk (HR)-HPV types.Study designBetween 2022 and 2023, 459 cervical samples from women undergoing cervical cancer screening were selected. These samples were analysed by liquid-based cytology and tested by both kits concurrently.ResultsAllplexTM HPV28 Ct values correlated well with AnyplexTM II HPV28 signal intensity scores. No significant differences between assays were observed in overall and genotype-specific HR-HPV prevalence determined in all samples and according to cytological results. In addition, no significant differences were identified between assays in the detection of single and multiple HR-HPV infections. Most of the discordant results corresponded to samples showing weak HR-HPV signals and multiple HR-HPV types.ConclusionsOur results demonstrate that the AllplexTM HPV28 kit can be used for HPV genotyping, with results overall similar to those obtained with the AnyplexTM II HPV28 kit and the addition of Ct values for patient follow-up. The clinical implications of the potentially reduced sensitivity of the AllplexTM HPV28 kit in detecting HPV31 (p = 0.07) and HPV39 (p = 0.08) warrant further investigation in subsequent studies.

The Société de Pathologie Infectieuse de Langue Française released in 2024 a new national recommendation for clinical practice on the prevention and management of varicella zoster virus (VZV) infection during pregnancy and the perinatal period. The previous recommendation was issued in 1998, at a time of anti-VZV immunoglobulins shortage; it has hence become obsolete. This recommendation is a formalized expert consensus focusing on infectious diseases management; it is drawn up by a multidisciplinary working group (infectiologists, obstetricians, pediatricians, microbiologists, midwives, hygienists). It has been endorsed by the Collège National des Gynécologues Obstétriciens Français, the Société Française de Médecine Périnatale, the Société Française de Néonatologie, the Collège des Sage-femmes, and the Groupe Infections et Périnatalité of the Société Française de Microbiologie. The aim of this article is to explain and recontextualize the elements of this recommendation.

Human cytomegalovirus (HCMV) is a major cause of morbidity in immunocompromised patients and the leading viral cause of congenital infection. The toxicity and emergence of resistance associated with current antivirals underscore the need for alternative therapeutic strategies. The viral terminase complex (pUL56-pUL89-pUL51), essential for genome cleavage and packaging and without homologs in mammalian cells, represents a promising antiviral target. This study evaluated the antiviral potential of peptides targeting the pUL56-pUL89 interaction domain. Peptides derived from the minimal interaction domain between pUL56 and pUL89 (WF10: 671WMVVKYMGFF680) or an extended sequence (PD17: 668PSEWMVVKYMGFFNFSD684) were synthesized to interfere with this interaction. To optimize intracellular delivery, peptides were conjugated to a cell-penetrating peptide (CPP) derived from either the HIV-1 transactivator of transcription (TAT) or the Antennapedia homeodomain of Drosophila melanogaster (penetratin; PT). Peptide candidates- PT-WF10, TAT-WF10, and PT-PD17- were evaluated in cellular models for cytotoxicity, hemolysis, antiviral activity, and intracellular distribution. TAT-WF10 and PT-PD17 significantly reduced the cytopathic foci in HCMV-infected cells, with IC50 values of 58 μM and 39 μM, respectively. PT-WF10 lacked antiviral activity, induced significant cytotoxicity and hemolysis, and was mainly localized in the cytoplasm, with only minimal nuclear signal. TAT-WF10 showed cytoplasmic and nuclear distribution, no hemolysis, but induced long-term cytotoxicity from 40 μM. PT-PD17 exhibited cytoplasmic and nuclear distribution, with no significant cytotoxicity or hemolysis up to 80 μM. This study provides the first proof of concept that a peptide targeting the pUL56-pUL89 interaction domain can inhibit HCMV replication. PT-PD17 demonstrated antiviral activity, intracellular distribution, and a favorable safety profile.

The Coronavirus pandemic unveiled the unprecedented need for diagnostic tests to rapidly detect the presence of pathogens in the population. Real-time RT-PCR and other nucleic acid amplification techniques are accurate and sensitive molecular techniques that necessitate quality control strategies and stable quality control materials. To meet this need, Twist Bioscience has developed and released synthetic RNA controls. However, RNA is an inherently unstable molecule needing cold storage, costly shipping, and resource-intensive logistics. Imagene provides a solution to this problem by encapsulating dehydrated RNA inside metallic capsules filled with anhydrous argon, allowing room temperature and eco-friendly storage and shipping. This technology initially developed for DNA storage has been successfully applied to RNA and other biospecimen and extensively validated through real time and accelerated aging. Here, RNA controls produced by Twist Bioscience were encapsulated in RNAshells and distributed to several laboratories that used them for COVID-19 detection tests by amplification. One RT-LAMP procedure, four different RT-PCR devices and 6 different PCR kits were used. The amplification targets were genes E, N; RdRp, Sarbeco-E and Orf1a/b. RNA retrieval was satisfactory, and the detection was reproducible. RNA stability was checked by real-time (3 years at room temperature) and accelerated aging (16 h at 90 °C, corresponding to approximately 10 years of storage at 25 °C, according to our previously published Arrhenius study for encapsulated RNA). The results were not significantly different from those for unaged capsules. This room temperature RNA stability allows the preparation and distribution of large strategic batches which can be stored for more than 10 years a long time and used for standardization processes between detection sites. Moreover, this provides the advantage of single-use and field usability across varying temperatures. Consequently, this type of encapsulated synthetic RNA, processed at room temperature, can be used as internal quality control materials for the SARS-Cov-2 virus as well as for detection of other RNA viruses.

Human coronavirus OC43 (HCoV-OC43) is predominantly associated with mild respiratory infections. HCoV-OC43 also has neuroinvasive properties, and severe encephalitis has been described in immunocompromised patients, with fatal outcomes due to the lack of specific antiviral treatment. We report a case of severe febrile encephalitis attributed to HCoV-OC43 that progressively worsened over 3 months in a 65-year-old immunocompromised man. Clinical symptoms improved remarkably after treatment with remdesivir, with an increase of the Glasgow Coma Score from 8 to 14 within 7 days.

Cytomegalovirus (CMV) remains the most important viral pathogen in patients after allogeneic haematopoietic cell transplantation (HCT), resulting in morbidity and mortality. The European Conference on Infections in Leukaemia (ECIL) brings together experts in several fields to produce evidence-based recommendations from comprehensive literature reviews. Management of CMV has been addressed twice before; the previous guideline update from the ECIL was published in 2019. The 10th ECIL meeting in 2024 addressed new developments in CMV management after allogeneic HCT, and recommendations are presented in this Review. Management recommendations include diagnostics, such as immune monitoring, antiviral prophylaxis with letermovir, management of resistant and refractory CMV infections, and paediatric aspects of CMV management. Furthermore, the 10th ECIL introduced recommendations for two new categories: patients treated with chimeric antigen receptor T cells or treated with bispecific T-cell-engaging antibodies.

PURPOSE:This study seeks to reassess and enhance the dosing strategies of letermovir and maribavir for treating cytomegalovirus (CMV) infection, aiming to propose adjustments that could improve therapeutic effectiveness. METHODS:Pre-existing population pharmacokinetic models were used alongside Monte Carlo simulations to evaluate the dosing strategies of letermovir and maribavir in CMV treatment. The simulations assessed the probability of target attainment for current and alternative dosing regimens, including scenarios with missed doses. RESULTS:For letermovir, a loading dose on the first day of treatment initiation appeared more effective than the current strategy without a loading dose. Additionally, in cases of missed doses, doubling the dose upon resumption was more effective than returning to the normal dosage. For maribavir, the current 400mg BID regimen only covers the lower end of the inhibitory concentration 50 range, suggesting a potential benefit from increasing the doses. Simulations indicated that for missed doses, all tested regimens only covered the lower range of inhibitory concentrations, but the current strategy of resuming the normal dosage provided the lowest chances of target attainment. CONCLUSION:Our findings suggest a strong rationale to reconsider and potentially modify the approved dosing guidelines for letermovir and maribavir in CMV treatment. Adjusting dosing regimens, including the use of loading doses and increased doses after missed doses, could enhance treatment outcomes by ensuring higher probabilities of achieving therapeutic targets and better managing missed doses.

Une nouvelle recommandation nationale pour la pratique clinique sur la prévention et la prise en charge de l’infection par le virus varicelle zona (VZV) pendant la grossesse et la période périnatale est parue en 2024, sous l’égide de la Société de Pathologie Infectieuse de Langue Française.La précédente recommandation, publiée en 1998 pendant une période de pénurie en immunoglobulines spécifiques, était devenue en effet obsolète.Il s’agit d’un consensus formalisé d’experts élaboré par un groupe de travail multidisciplinaire (infectiologues, obstétriciens, pédiatres, microbiologistes, sage-femme, hygiénistes), dont le champ est infectiologique.Cette recommandation a été endossée par le Collège National des Gynécologues Obstétriciens Français, par la Société Française de Médecine Périnatale, par la Société Française de Néonatologie, par le collège des Sage-femmes, et par le Groupe Infections et Périnatalité de la Société Française de Microbiologie.L’objectif de cet article est d’expliciter, en les recontextualisant, les éléments de cette mise à jour.

Human cytomegalovirus (HCMV) is one of the most important causes of complications in immunocompromised patients and congenital infections. HCMV could also represent an interesting target for treatment to limit the progression of glioblastoma, a highly aggressive tumor. Ganciclovir, foscarnet and cidofovir, which interfere with the activity of the viral polymerase pUL54, are widely used in the treatment of transplant patients. However, their use in pregnant women remains limited or even contraindicated. On the other hand, hyperimmune immunoglobulins and valaciclovir have been shown to have a protective effect on the fetus. However, the toxicity of these treatments and the emergence of resistance mean that new therapeutic strategies need to be identified. Letermovir and maribavir have been developed to inhibit new targets, respectively the terminase complex and UL97 protein kinase. Their respective indications are the prevention of HCMV infection in haematopoietic stem cell transplant patients and the treatment of refractory HCMV infections. Finally, with the development of mRNA vaccines, the hope of one day seeing a prophylactic HCMV vaccine has never been greater. New therapeutic approaches are also being explored, but they still require extensive preclinical and clinical evaluation.