ABSTRACT Background Cytomegalovirus (CMV) infection remains a common complication after kidney transplantation, particularly among high‐risk donor‐seropositive/recipient‐seronegative (D+/R−) recipients. Valganciclovir is the standard first‐line therapy; however, its use may be limited by hematological toxicity or impaired graft function. Maribavir is a recently approved antiviral agent with a distinct mechanism of action. Case Presentation We report four high‐risk kidney transplant recipients in whom maribavir was introduced because continued valganciclovir therapy was difficult owing to cytopenia or renal dysfunction. After switching therapy, CMV viral loads decreased in all cases, and hematological abnormalities improved following discontinuation of valganciclovir. One patient developed a drug‐induced skin eruption, while no other serious adverse events were observed. No CMV recurrence or graft dysfunction occurred during follow‐up. Conclusion These cases highlighted practical clinical considerations for managing CMV infection when standard antiviral therapy cannot be safely continued.

Is It Justified to Order an Upfront Cytomegalovirus Immunohistochemical Stain in Patients with Severe Inflammatory Bowel Disease and Ulceration?

Cytomegalovirus immune globulin (CMVIG) reduces severe Cytomegalovirus (CMV) associated disease in liver transplant recipients (LTR). Because CMV viral loads (VL) were not available when the original prophylaxis trial was conducted, we retrospectively assessed CMV disease severity and CMV VL patterns in moderate and low-risk LTR receiving CMVIG prophylaxis. CMV VLs were measured using a quantitative PCR assay (Eurofins Viracor) in stored serial serum specimens from 96 LTR (D-/R- and R +). CMV-associated disease was classified according to original trial definitions and stratified by CMV disease severity. CMV outcomes and VL parameters were compared between CMVIG and placebo groups. 96 patients out of the original 146 study subjects had available serum samples for analysis. 67 (70%) had at least 1 detectable CMV VL. Severe CMV disease (vs. CMV syndrome/asymptomatic CMV disease) was associated with higher peak CMV VLs (p < 0.0001), shorter times to first detectable CMV VL (p = 0.01), and increased mortality (p = 0.003). Compared to placebo, CMVIG recipients had longer times to peak CMV VL (median days 38 vs. 35; log-rank p = 0.049), lower rates of CMV pneumonitis (0% vs. 17.6%, p = 0.01) and fewer cases of severe CMV disease (3% vs. 17.6%, p = 0.04). Using specimens from studies preceding the antiviral prophylaxis era, among moderate- and low-risk LTR, CMVIG prophylaxis was associated with attenuated CMV disease severity and delayed progression of CMV viremia. These findings suggest that CMVIG may offer both clinical and limited antiviral benefits in this population, particularly in settings where standard antiviral prophylaxis cannot be used.

Pharmacokinetics and pharmacodynamics of valganciclovir in infants with severe HIV-associated pneumonia in Africa: a sub-study of the EMPIRICAL randomised controlled trial.

Purpose: This study aimed to evaluate the clinical and laboratory features of cytomegalovirus (CMV) reactivation in immunosuppressed patients with rheumatic diseases and to compare the characteristics of patients with and without mortality. Materials and Methods: This retrospective cohort study included 30 adult patients with rheumatic diseases who were receiving immunosuppressive therapy and underwent CMV polymerase chain reaction (PCR) testing due to clinical and/or laboratory suspicion between November 2016 and April 2024. Patients with CMV PCR positivity were included in the analysis. Demographic, clinical, and laboratory data were collected. Comparisons of clinical and laboratory parameters were conducted according to antiviral treatment use and survival status. Results: Granulomatosis with polyangiitis (23%) and adult-onset Still’s disease (20%) were the most frequent underlying diagnoses. CMV reactivation predominantly occurred during periods of intensive immunosuppressive therapy. Antiviral treatment with ganciclovir was administered in 70% of patients, who had higher CMV viral loads, lower lymphocyte and albumin levels, and higher C-reactive protein levels compared with untreated patients. The overall mortality rate was 23.3%. In multivariable analysis, CMV-associated pneumonia was the only variable independently associated with mortality. Conclusion: CMV reactivation is a serious complication in immunosuppressed patients with rheumatic diseases and is associated with substantial mortality, particularly in the presence of pulmonary involvement.

Cytomegalovirus (CMV) infection is a common complication following solid organ transplantation and is associated with significant morbidity. While CMV classically presents with systemic symptoms, bone marrow suppression or gastrointestinal disease, atypical manifestations may occur. Anasarca and refractory ascites in liver transplant recipients are more commonly attributed to graft dysfunction, vascular complications, cardiac disease or renal pathology, and CMV is not often considered as a primary aetiology. A 63-year-old woman with a history of alcohol-related cirrhosis underwent deceased donor liver transplantation and later presented with progressive abdominal distension and bilateral lower extremity oedema. Evaluation demonstrated tense ascites and anasarca without evidence of graft dysfunction, acute rejection, portal vascular complications, cardiac disease or nephrotic syndrome. Liver function tests were normal, transthoracic echocardiography revealed preserved systolic function, and urinalysis was negative for proteinuria. Further workup identified CMV viremia, and the patient was treated with valganciclovir per infectious disease recommendations, along with supportive measures including diuresis and large-volume paracentesis. Serial monitoring demonstrated improvement in CMV viral load with corresponding gradual resolution of fluid retention. This case highlights CMV viremia as an important and potentially reversible cause of anasarca in post-liver transplant patients, likely mediated by CMV-induced endothelial dysfunction. Recognition of CMV-related fluid retention is essential to avoid unnecessary invasive procedures and to guide timely antiviral therapy in immunosuppressed individuals. Cytomegalovirus (CMV) infection should be considered in the differential diagnosis of unexplained anasarca and refractory ascites in liver transplant recipients, even in the absence of graft dysfunction or classic CMV symptoms.A systematic evaluation to exclude cardiac, renal, vascular and graft-related causes of fluid overload is essential before attributing post-transplant anasarca to non-infectious aetiologies.Early recognition and treatment of CMV viremia can lead to clinical improvement and optimise outcomes in immunosuppressed patients.

Non-hepatotropic viruses (NHVs), as a category of pathogens not primarily targeting the liver, can also cause hepatic injury. Liver injury associated with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, in particular, often attracts significant clinical attention. This retrospective cohort study analyzed the seroprevalence and clinical features of EBV and CMV infections among patients in Beijing from 2020 to 2024, with a focus on the impact of immunosuppression status on liver injury patterns. The CMV IgM positivity rate was 4.00% (646/16,201), and the EBV IgM positivity rate was 7.84% (1007/12,838), both showing significant upward annual trends (p < 0.001). Analysis of 236 IgM-positive inpatients revealed a "bifurcation phenomenon": the non-immunosuppressed group exhibited more severe hepatocellular injury (e.g., ALT levels 6.5- to 10.9-fold higher) and cholestatic damage (e.g., CMV group: TBIL increased 7.8-fold), yet had better clinical outcomes (adverse outcome rate: 0-4.8%) compared to the immunosuppressed group (adverse outcome rate: 18.4-27.8%, p < 0.05). Further analysis of 125 patients with confirmed liver injury demonstrated that the immunosuppressed group had severe CD4 + T-cell depletion and inverted CD4 + /CD8+ ratios. During EBV and CMV co-infection, the immunosuppressed group showed higher CMV DNA detection rates (66.7% vs. 20.0%, p = 0.0097) and viral loads (median 2675 vs. 625 copies/mL, p = 0.002). Within the immunosuppressed group, patients with CD4 + T-cell counts > 300 cells/μL had higher ALT and AST levels, supporting an immune-mediated injury mechanism. These findings indicate that immune status and virus type jointly shape the clinical spectrum of EBV/CMV-related liver injury. The dissociation between severe liver injury and favorable prognosis in non-immunosuppressed patients underscores the role of immune pathology, while poorer outcomes in immunosuppressed patients are driven by CD4 + T-cell depletion, impaired viral clearance, and extrahepatic complications.

To introduce an atypical occlusive panretinal vasculitis without necrotizing retinitis secondary to cytomegalovirus (CMV) infection as the heralding clinical event for a patient ultimately discovered to have Good Syndrome, a systemic immunodeficiency. Case report. A 77-year-old male with a history of hypertension, diabetes mellitus, recurrent sinusitis, and oral thrush presented with 3 weeks of headaches and vision loss (20/250) in the right eye. Examination revealed panuveitis, scattered mid-peripheral intraretinal hemorrhages without retinal necrosis, profound retinal vascular nonperfusion, and elevated IOP due to anterior segment neovascularization. Aqueous humor viral PCR analysis revealed a high CMV viral load. Systemic evaluation was negative for HIV, CMV, toxoplasmosis, and syphilis; carotid duplex imaging was normal, leukemia and lymphoma studies were negative; and he was not neutropenic. CD4+ count and immunoglobulin levels were decreased, suggesting a combined B- and T-cell immunodeficiency. Computed tomography of the chest revealed a thymoma, consistent with Good Syndrome, a rare immunocompromising condition. Antiviral therapy did not significantly reverse retinal perfusion. Panretinal occlusive vasculitis without retinal necrosis is a rare phenotype of CMV retinitis. In HIV-negative patients with CMV retinitis, additional immunodeficiency workup is required, and rare combined immunodeficiencies such as Good Syndrome should be included on the differential.

Abstract Background Cytomegalovirus (CMV) is a latent herpesvirus that can reactivate under conditions of immunosuppression, a phenomenon of particular relevance in patients with inflammatory bowel disease (IBD). Its reactivation in ulcerative colitis (UC) has been associated with more severe disease forms, especially in corticosteroid-refractory cases with poorer clinical outcomes. Our objective was to evaluate the clinical impact of CMV infection in patients with UC and Crohn’s disease (CD) by analyzing its relationship with treatment modification, hospitalization risk and need for surgery. Methods A retrospective case–control study (2019–2023) was conducted on patients with UC and CD followed at Hospital Clinic Barcelona. Colon biopsies were assessed by histology and microbiology (PCR). Results A total of 209 patients were included, of whom 72 tested positive for CMV (34.4% by PCR, and only 7.2% by histology). All CMV-positive cases received antiviral therapy. CMV-positive UC patients had higher clinical activity scores (Mayo and UC PRO-2) (p &amp;lt; 0.05) compared with CMV-negative controls, with no differences in endoscopic activity (Mayo subscore). In CD, CMV-positive cases had more liquid stools (p = 0.0448) compared with CMV-negative controls, but no differences in endoscopic severity (SES-CD). Erythrocyte sedimentation rate (ESR) was the only independent predictor of CMV positivity (OR = 1.028; p = 0.0006). Logistic regression analysis revealed a statistically significant association between CMV viral load and the probability of CMV-related hospitalization (p = 0.0363). CMV-positive patients required fewer treatment modifications (38.9% vs. 63.5%; p = 0.0007), with no significant differences in surgery or hospitalization rates during a median follow-up period of three years. Conclusion CMV infection is associated with greater clinical severity in UC, though not with increased endoscopic severity. Detection is more sensitive by PCR than by immunohistochemistry on paraffin-embedded tissue. Treatment of CMV infection (in both UC and CD) is associated with fewer changes in baseline IBD therapy. These findings support systematic CMV screening by PCR in moderate-to-severe flares to improve clinical management.

Cytomegalovirus (CMV) reactivation occurs in the context of coronavirus disease 2019 (COVID-19); however, the viral kinetics, risk factors, and clinical outcomes are poorly defined. We examined the association of CMV DNAemia with clinical outcomes among participants of a randomized trial of remdesivir with or without baricitinib (National Institute of Allergy and Infectious Diseases [NIAID], Adaptive COVID-19 Treatment Trial 2 [ACTT-2]). Plasma CMV DNAemia from CMV-seropositive participants with COVID-19 (NIAID ordinal scale [OS] 5, 6, or 7 at entry) were assessed longitudinally by quantitative polymerase chain reaction. Factors associated with CMV DNAemia, and clinical outcomes were analyzed by Cox regression and proportional odds models. Of 772 trial participants with available samples, 643 (83%) were CMV seropositive. Baseline CMV serostatus was not associated with COVID-19 outcomes. The cumulative incidence of CMV DNAemia among seropositive persons by day 28 was overall 11% (baseline OS 5, 6.3%; OS 6, 16.4%; OS 7, 24.7%), and was associated with older age, baseline OS, male sex, lymphopenia, and systemic corticosteroid use, while remdesivir and baricitinib did not affect risk. CMV DNAemia was associated with a lower probability of improvement by day 29 (adjusted hazard ratio, 0.3 [95% confidence interval, .17-.56]), with a more pronounced delay of recovery with higher CMV viral load. CMV DNAemia was also associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and death. In hospitalized adults with COVID-19 requiring oxygen, CMV viremia occurs within well-defined clinical risks and is independently associated with delayed recovery from illness, higher SARS-CoV-2 viral load, and increased mortality.

Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss in children. Recent evidence that high-dose valacyclovir reduces vertical transmission following primary maternal infection has renewed the urgency for screening. We investigated the utility of quantifying cell-free CMV DNA from noninvasive prenatal screening (NIPS) data to identify pregnancies at risk for primary CMV infection and cCMV. In this retrospective study, we analyzed NIPS data from 22 333 unselected pregnancies at 12 weeks gestation. CMV-aligned reads were quantified from low-pass whole-genome sequencing data and validated against quantitative PCR (qPCR) for viral load, maternal serology for infection status and systematic newborn screening for cCMV. CMV read counts demonstrated good correlation with qPCR-measured viral loads (rs = 0.76; 95%CI: 0.68-0.81). Presence of ≥1 CMV read count (2.1% of pregnancies) was highly predictive of cCMV [likelihood ratio (LR) = 21.1; 95% confidence interval (CI): 14.9-30.1]. CMV read counts showed good diagnostic accuracy for primary infection [area under the receiver operator characteristic curve (AUROC) = 0.77; 95% CI: 0.72-0.82] and for cCMV (AUROC = 0.82; 95% CI: 0.76-0.86). A threshold of ≥4 read counts identified a subgroup with significantly elevated risk for primary infection (LR = 7.8; 95% CI: 4.3-14.2) and cCMV (LR = 6.0; 95% CI: 3.3-10.8), achieving positive predictive value for cCMV of 51.7%. Quantification of CMV DNA during NIPS is an accurate and sensitive method for CMV viral load. This approach effectively stratifies risk for both primary maternal infection and cCMV, enabling identification of pregnancies that may benefit from antiviral therapy.

Immune responses may determine natural history and optimal management of cytomegalovirus (CMV) reactivation following allogeneic hematopoietic cell transplantation (alloHCT). To assess this, we performed serial QuantiFERON-CMV (QFCMV, Qiagen) and QuantiFERON-Monitor (QF-monitor, Qiagen) tests, measuring CMV-specific T cell interferon-γ responses (IFNγ), and stimulators of innate (TLR7) and adaptive immunity (CD3), respectively. In a prospective multicenter study of adult CMV-seropositive alloHCT recipients, QFCMV and QF-monitor tests were collected serially. Association with CMV outcomes was analyzed using multivariable Cox and mixed effects regression analysis. Overall, 119 patients had 385 QFCMV tests (median [IQR]:3 [3-4] per patient). csCMVi occurred in 45.4% patients. QFCMV reactivity was achieved in 16% of patients at 6 weeks, 38.3% at 12 weeks, and 40.2% any time during the study. Reactivity was predictive of lower peak CMV viral load in the 6 weeks following testing (-0.41×log10 [95% CI -0.77 to -0.04×log10], p=0.02), but did not impact csCMVi. Analysis of mitogen-stimulated IFNγ responses within QFCMV testing showed reduced risk of csCMVi in the following 6 weeks (adjusted HR 0.92 [95% CI 0.85-0.99], p=0.025) and each 1IU/mL IFNγ increase was associated with decreased peak viral load (-0.02×log10 [95% CI -0.03 to 0.00×log10], p=0.02). QF-monitor was not associated with any CMV outcomes. QFCMV reactivity was associated with lower peak CMV viral load but not csCMVi. Mitogen-stimulated IFNγ response correlated with csCMVi, suggesting a role for broader assessment of cellular immunity post-transplant. Despite incorporating adaptive immunity measures, QF-monitor was limited in assessing CMV risk. QFCMV reactivity was infrequently achieved in the early post-allogeneic stem cell transplant period. Qualitative QFCMV result was associated with peak CMV viral load but not clinically significant infection, while magnitude of the mitogen response predicted reduction in clinically significant CMV infection.

Cytomegalovirus (CMV) infection is a major cause of morbidity in immunocompromised patients, particularly those living with Human Immunodeficiency Virus (HIV). This study describes the clinical manifestations, diagnostic approaches, and therapeutic challenges of CMV infection in HIV patients in Morocco. A descriptive retrospective study was conducted on seventeen (17) HIV patients with CMV infection, diagnosed by real-time Polymerase Chain Reaction (PCR). Clinical, virological (HIV and CMV viral load, CD4 count), and therapeutic data were subsequently analysed. The mean age was 43 ± 10.7 years, with male predominance (94.1%). Digestive manifestations (29.4%) were the most frequent, followed by respiratory and neurological involvement (17.6% each). The mean CD4 count was 65.4 ± 56.2 cells/mm³. The mean CMV viral load was 2.39 ± 0.74 Log and the mean HIV viral load was 4.10 ± 1.55 Log. Antiviral therapy for CMV could not be initiated in 47% of patients due to its unavailability. The outcome was favorable in 88.2% of patients, with a mortality rate of 11.8%. In conclusion; CMV infection in HIV patients in Morocco occurs in the context of severe immunosuppression and presents with a varied clinical spectrum, dominated by digestive pathologies. Real-time PCR remains crucial for diagnosis. The unavailability of antiviral drugs constitutes a major challenge for management, highlighting the need to improve access to treatments in resource-limited settings.

Cytomegalovirus (CMV) reactivation remains a common and serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), often leading to significant morbidity and mortality in immunocompromised recipients. Adoptive transfer of CMV-specific cytotoxic T lymphocytes (CMV-CTLs) has emerged as a promising immunotherapeutic approach to restore antiviral immunity and prevent CMV-related complications. This interim analysis of a randomized phase I-II clinical trial evaluates the safety and preliminary efficacy of prophylactic infusion of donor-derived CMV-CTLs administered early after allo-HSCT. Twenty adult allo-HSCT recipients were randomized 1:1 to receive either standard care (control group) or a single intravenous infusion of 10 million donor-derived CMV-CTLs per m2 of body surface area (intervention group) between days + 14 to + 21 post-transplant. The primary endpoint was safety, defined by infusion-related adverse events and incidence of acute graft-versus-host disease (aGvHD). Secondary endpoints included incidence and kinetics of CMV reactivation, measured by serial quantitative RT-PCR during the first 90days post-transplant. Baseline characteristics were balanced between the two groups. No grade 3-5 adverse events were observed following CMV-CTL infusion. aGvHD grade II occurred in 30% of the intervention group versus 40% in controls. The incidence of CMV reactivation at 90days was lower in the intervention group (52.00%) compared to controls (77.78%), although not statistically significant (P = 0.580). However, CMV viral loads were significantly lower over time in the intervention group (P = 0.028), suggesting a favorable antiviral effect of CMV-CTLs. Prophylactic infusion of donor-derived CMV-CTLs early after allo-HSCT appears safe and may reduce CMV reactivation and viral burden. These findings support the potential of CMV-CTLs as a novel immunotherapeutic strategy for CMV management in high-risk transplant recipients. Further validation in larger, multicenter trials is warranted.

Novel use of low-dose cidofovir (2.5 mg/kg Weekly) as CMV prophylaxis in the pre-engraftment Phase of stem cell transplantation: A viable alternative when ganciclovir is contraindicated and letermovir is not available

Incidence of CMV-reactivation in multiple myeloma patients receiving bispecific antibodies

Cytomegalovirus reactivation among immunocompetent patients hospitalized in medical intensive care: Associated factors and consequences.

BackgroundDelayed graft function (DGF) is a significant risk factor for renal allograft failure. This study aimed to estimate the incidence of cytomegalovirus (CMV) infection and investigate whether DGF is associated with an increased risk of CMV infection in renal transplant recipients.MethodsIn this single-center, retrospective cohort study, we analyzed CMV outcomes in deceased donor renal transplant recipients with and without DGF. Univariate and multivariate odds ratio were calculated using a Cox proportional hazards model.ResultsData from 124 recipients (mean age: 44.72±9.97 years; 89 males) were evaluated. Cytomegaloviruria was diagnosed in 16 patients (12.9%) within one year post-transplantation. Patients with DGF exhibited a significantly higher risk of cytomegaloviruria compared to those without DGF (P=0.02). Additionally, the DGF group demonstrated lower lymphocyte proportions and absolute CD4+ T cell counts than the non-DGF group (P=0.03 and P=0.01, respectively).ConclusionsOur findings suggest that renal transplant recipients with DGF are at an increased risk of developing cytomegaloviruria. These results highlight the need for prospective studies to evaluate the utility of monitoring CMV viral loads and CD4+ T lymphocyte counts in patients with DGF to guide clinical management.

Monitoring of viral load is of critical importance in the clinical management of patients at risk of cytomegalovirus (CMV)-related complications following transplantation. Quantitative real-time polymerase chain reaction (qRT-PCR) is one of the most commonly used methods for CMV DNA detection. For this purpose, commercial test kits calibrated according to the International Standard of Quantitation (ISQ) defined by the World Health Organization (WHO) are used. However, measurement variability between different test systems still constitutes a significant problem. The aim of this study was to compare the test results of two different commercial kits, CMV Cobas Ampliprep/Cobas Taqman (CMV-CAP/CTM) (Roche Diagnostics, Mannheim, Germany) and NeuMoDx CMV Quant Assay (Qiagen, Ann Arbor, USA) which have been calibrated with the WHO CMV IQS. The results of 478 plasma samples run simultaneously with the CMV-CAP/CTM and NeuMoDx CMV PCR tests were analyzed. Fully automated steps including extraction, real-time amplification and result analysis were performed according to the manufacturer’s recommendations. CMV DNA was detected in 216 (45.18%) samples and not detected in 82 (17.15%) samples in both tests. A total of 180 (37.65%) samples had discordant results. Statistically, a moderate level of qualitative agreement was found between the qualitative results of both tests (kappa= 0.28, p< 0.001). When the quantitative results obtained in the dynamic measurement range of both tests (n= 104) were examined, the median viral load values measured by CMV-CAP/CTM and NeuMoDx CMV tests were calculated as 1598 IU/mL (range= 137.41-115570) and 2600 IU/mL (range= 55-220000), respectively. According to the correlation analysis, a very strong correlation was found in the comparison of the results of both tests (r= 0.83, p< 0.001). According to the Bland-Altman analysis; the average difference between the CMV-CAP/CTM test and NeuMoDx CMV test values was found to be 0.296 log10 (standard deviation: 0.412) IU/mL (the lowest difference was 0.005 and the highest difference was -1.559 log10 IU/mL), and the CMV-CAP/CTM test gave lower measurements than the NeuMoDx CMV test. In 104 samples with results in the dynamic measurement range of both tests, for log10 IU/mL results, the measurement difference was within ±0.5 log10 IU/mL in 71 (quantitative agreement: 68.3%) samples and the measurement difference was greater than ±0.5 log10 in 33 (31.7%) samples (median= 0.7 log10 IU/ml; range: 0.51-1.56). A measurement difference of more than ±1 log10 was detected in two samples (1.9%). As a result, in the measurements made with CMV-CAP/CTM and NeuMoDx CMV PCR tests, a moderate level of agreement was found for qualitative results in plasma samples, a strong correlation for quantitative values and a biologically significant viral load difference in one-third of the samples was detected. Our study shows that the measurement differences observed between CMV PCR test platforms do not completely disappear even if calibration is provided with the WHO ISQ. In post-transplantation follow-up, considering the measurement differences between test systems and preferring the same sample type and the same test platform in CMV viral load monitoring is important in terms of ensuring consistency in patient management.

Ganciclovir (GCV) is commonly used to treat cytomegalovirus (CMV) infections in immunocompromised children. Currently, the therapeutic target for effective treatment is unclear: Adult studies suggest that a serum area under the concentration-time curve (AUC24h) ≥40 mg/L·h correlates with effective CMV prevention. The aim of this study was to determine the serum GCV therapeutic target for the treatment of CMV viraemia in immunocompromised children. Data from a multicenter retrospective audit of GCV dosing, therapeutic drug monitoring and plasma CMV viral loads in immunocompromised children were analysed using piecewise linear regression to determine viral dynamics during GCV treatment periods. A published population pharmacokinetic model from the same cohort was used to derive post hoc average daily AUC24h. An Emax model was developed in NONMEM to explore the effect of drug exposure on viral dynamics, adjusting for immune status. Fourteen children with 185 viral loads were included, encompassing 30 periods of viral load increases and 28 periods of decline. The estimated natural viral replication rate was 0.237 log10 copies/mL/day (doubling time 1.3days). White cell count (WCC) significantly affected the viral decline rate, with a maximum GCV-induced viral decline rate of 0.238 log10 copies/mL/day. The GCV AUC24h corresponding to 90% maximal replication suppression and elimination effects were approximately 40 and 100 mg/L·h, respectively, when the WCC was 3.7 × 109/L. A serum GCV AUC24h target of 40-100 mg/L·h may serve as a preliminary reference for the treatment of CMV infection in immunocompromised children. Notably, the therapeutic target is affected by the individual's immune status.