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The British Journal of Ophthalmology Dec 2021While cytomegalovirus (CMV) anterior uveitis (AU) patients often require glaucoma surgery, the effectiveness of systemic anti-viral in long-term intraocular pressure...
BACKGROUND/AIMS
While cytomegalovirus (CMV) anterior uveitis (AU) patients often require glaucoma surgery, the effectiveness of systemic anti-viral in long-term intraocular pressure (IOP) control is not well established. Our study aims to identify the 2-year efficacy and safety of oral valganciclovir in CMV AU with uncontrolled IOP.
METHODS
In this retrospective case series, one eye from each of 17 immunocompetent PCR-proven patients with CMV AU who received a single course of oral valganciclovir for 20-148 days for medically uncontrolled IOP during 2008-2018 were identified. They were examined at baseline, week 2, months 1, 2 and 3, then every 3 months up to 2 years after commencement of valganciclovir, or until IOP-lowering procedure.
RESULTS
Median baseline IOP and IOP-lowering medication were 27.0 mm Hg (IQR: 22.9-31.0 mm Hg), and 4.0, respectively. IOP was significantly lower than baseline from 2 weeks to 12 months and at 21 and 24 months after starting valganciclovir (p=0.001 to 0.041, Wilcoxon sign-rank test), with 16.9-46.0% median IOP reduction. Seven (41.2%) and six (35.3%) patients had IOP≤21 mm Hg with same, or reduced, topical medications by 12 and 24 months, respectively. Median time to IOP-lowering intervention or second course of valganciclovir was 12.4 months. There was no serious medication-related adverse event. Common side effects included reduced monocyte count (9 patients) and deranged renal function/electrolytes (5 patients). IOP spike and wound leak occurred in 35.5% and 29.4% of patients, respectively, after diagnostic aqueous tap.
CONCLUSION
In CMV AU with uncontrolled IOP, >1/3 of the patients avoided glaucoma surgery over 2 years with a course of oral valganciclovir.
Topics: Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Glaucoma; Humans; Intraocular Pressure; Retrospective Studies; Treatment Outcome; Uveitis, Anterior; Valganciclovir
PubMed: 33011687
DOI: 10.1136/bjophthalmol-2020-317044 -
PloS One 2009Several anti-viral drugs have demonstrated efficacy in preventing Cytomegalovirus (CMV) infections in solid organ transplant (SOT) patients. The recently approved... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several anti-viral drugs have demonstrated efficacy in preventing Cytomegalovirus (CMV) infections in solid organ transplant (SOT) patients. The recently approved valganciclovir is the most commonly used and most expensive drug for CMV prevention. The safety and efficacy data have been drawn from a single trial. We hypothesized that valganciclovir may not be as safe as nor more effective than other therapies for CMV prevention.
METHODS
All experimental and analytical studies that compared valganciclovir with other therapies for prevention of CMV infection after SOT were selected. Based on meta-analytic and multivariate regression methodologies we critically analyzed all available evidence.
FINDINGS
Nine studies were included (N = 1,831). In trials comparing valganciclovir with ganciclovir, the risk for CMV disease is 0.98 (95% Confidence Interval (95%CI) 0.67 to 1.43; P = 0.92; I(2) = 0%). Valganciclovir was significantly associated with the risk of absolute neutropenia (<1,500/mm(3)) compared with all therapies (Odds Ratio (OR) 3.63 95%CI 1.75 to 7.53; P = 0.001; I(2) = 0%); with ganciclovir only (OR 2.88, 95%CI 1.27 to 6.53; P = 0.01; I(2) = 0%); or with non-ganciclovir therapies (OR 8.30, 95%CI 1.51 to 45.58; P = 0.01; I(2) = 10%). For a neutropenia cut-off of <1,000/mm(3), the risk remained elevated (OR 1.97, 95%CI 1.03 to 3.67; P = 0.04; I(2) = 0%). For every 24 patients who receive valganciclovir prophylaxis, one more will develop neutropenia compared to other therapies. The risk of late-onset CMV disease with valganciclovir was similar to ganciclovir and higher than those with non-ganciclovir therapies (OR 8.95, 95%CI 1.07 to 74.83; P = 0.04; I(2) = 0%]. One more patient will develop late-onset CMV disease for every 25 who receive valganciclovir compared to treatment with non-ganciclovir therapies. The risk of CMV tissue-invasive disease in liver recipients receiving valganciclovir was 4.5 times the risk seen with ganciclovir [95%CI 1.00 to 20.14] (p = 0.04). All results remained consistent across different study designs, valganciclovir doses, and CMV serostatus.
CONCLUSIONS
Valganciclovir shows no superior efficacy and significantly higher risk of absolute neutropenia, CMV late-onset disease, and CMV tissue-invasive disease compared to other standard therapies. Due to the availability of efficacious, safer, and lower cost drugs (high-dose acyclovir, valacyclovir, ganciclovir), our results do not favor the use of valganciclovir as a first-line agent for CMV preemptive or universal prophylaxis in SOT patients.
Topics: Antiviral Agents; Case-Control Studies; Cohort Studies; Cytomegalovirus; Cytomegalovirus Infections; Evidence-Based Medicine; Female; Ganciclovir; Humans; Male; Middle Aged; Organ Transplantation; Randomized Controlled Trials as Topic; Valganciclovir
PubMed: 19436751
DOI: 10.1371/journal.pone.0005512 -
Transplant Infectious Disease : An... Aug 2021Immunomodulatory effects attributable to cytomegalovirus (CMV) would predispose to BK polyomavirus (BKPyV) infection after kidney transplantation (KT), although...
BACKGROUND
Immunomodulatory effects attributable to cytomegalovirus (CMV) would predispose to BK polyomavirus (BKPyV) infection after kidney transplantation (KT), although available evidence is conflicting. It has been suggested that (val)ganciclovir therapy may increase the risk of BKPyV viremia and BKPyV-associated nephropathy (BKPyVAN) as a result of drug-induced T-cell impairment.
METHODS
We investigated whether CMV replication and/or (val)ganciclovir exposure (either as prophylaxis or treatment) were associated with the development of BKPyV viremia or BKPyVAN in a prospective cohort of 399 KT recipients. CMV infection (any level or high-level viremia and area under the curve of DNAemia) and (val)ganciclovir exposure (any duration of therapy and cumulative days of treatment) during the first post-transplant year were explored through separate landmark survival analyses.
RESULTS
Cumulative incidence of BKPyV viremia and BKPyVAN after a median follow-up of 551 days was 23.1% and 2.5%, respectively. One-year rates of CMV infection and (val)ganciclovir therapy were 47.4% and 54.1%, respectively. No differences were observed in BKPyV viremia- or BKPyVAN-free survival according to previous CMV infection or (val)ganciclovir exposure in any of the landmark analyses. Adjusted Cox models confirmed this lack of association.
CONCLUSION
Our findings do not confirm the existence of a relevant impact of CMV infection or (val)ganciclovir therapy on the risk of post-transplant BKPyV events.
Topics: Antiviral Agents; BK Virus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Nephritis, Interstitial; Polyomavirus Infections; Prospective Studies; Tumor Virus Infections; Valganciclovir; Viremia
PubMed: 33751753
DOI: 10.1111/tid.13597 -
Biological & Pharmaceutical Bulletin 2022The aim of this study was to investigate whether low-dose valganciclovir (VGCV) prophylaxis for cytomegalovirus (CMV) infection increased the risk of developing...
The aim of this study was to investigate whether low-dose valganciclovir (VGCV) prophylaxis for cytomegalovirus (CMV) infection increased the risk of developing neutropenia in heart transplant recipients (HTRs). Forty-three HTRs receiving VGCV were divided into two groups: those who received VGCV prophylaxis (n = 22) and those who did not (n = 21). Neutropenia was defined as an absolute neutrophil count ˂1500/µL and was monitored for approximately one year post-transplantation. In the prophylaxis group, 77.3% (17/22) of HTRs experienced neutropenia, which was significantly higher than that in the no prophylaxis group (42.9% [9/21], p = 0.031). No significant differences in the duration of VGCV administration and cumulative dose up to the first neutropenia episode were observed between the groups. Meanwhile, the cumulative dose of mycophenolate mofetil was significantly higher in the prophylaxis group than in the no prophylaxis group (p = 0.018); the daily maintenance dose and regularly measured area under the concentration-time curve (AUC) of mycophenolic acid did not significantly differ between groups. In conclusion, the risk of developing neutropenia was higher in HTRs receiving low-dose VGCV prophylaxis than it was in those not receiving prophylaxis, probably not attributed to dosing period and cumulative dose of VGCV until the onset of neutropenia.
Topics: Antiviral Agents; Ganciclovir; Heart Transplantation; Humans; Neutropenia; Risk Assessment; Valganciclovir
PubMed: 35370269
DOI: 10.1248/bpb.b21-00860 -
Clinical and Experimental Immunology Feb 2024Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to... (Randomized Controlled Trial)
Randomized Controlled Trial
Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) in T cells. Two treatment schedules were used: an experimental regime (ER) and a conventional treatment (CT). Mononuclear cells from patients with DKS/HIV were obtained at baseline (W0), 4 (W4), and 12 weeks (W12). Ten DKS/HIV patients received CT (antiretroviral therapy [cART]) and 10 ER (valganciclovir [VGC] initially, plus cART at the fourth week). HIV+ without KS and HIV- patient groups were included as controls. Correlation between T-cell subsets and HHV-8 viral load (VL) and a multivariate linear regression was performed. Data showed that DKS/HIV patients have an increased frequency of CD8+ T cells, which display a high density of CD8 expression. The ER scheme increases naïve and central memory CD4+ T cells at W4 and W12 of follow-up and induces a balanced distribution of activated CD4+ T-cell subsets. Moreover, ER decreases solTNFR2 since W4 and CT decreased the transmembrane forms of TNF axis molecules. Although CT induces a positive correlation between HHV-8 VL and TNFRs, the use of ER positively correlates with TNF and TNFRs levels through follow-up and a moderate correlation with HHV-8 VL and TNF soluble levels. In conclusion, VGC, as an add-on therapy in DKS/HIV patients, gradually modulates the activation of CD4+ T-cell subsets and the TNF/TNFRs axis, suggesting a better regulation of the inflammatory status.
Topics: Humans; Sarcoma, Kaposi; HIV Infections; Valganciclovir; CD4-Positive T-Lymphocytes; T-Lymphocyte Subsets; CD8-Positive T-Lymphocytes; Tumor Necrosis Factor-alpha; Viral Load; Sulfonamides
PubMed: 37904542
DOI: 10.1093/cei/uxad115 -
A Phase I Randomized, Controlled, Clinical Trial of Valganciclovir in Idiopathic Pulmonary Fibrosis.Annals of the American Thoracic Society Aug 2021Human herpesviruses Epstein-Barr virus and cytomegalovirus are frequently detectable in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and could... (Randomized Controlled Trial)
Randomized Controlled Trial
Human herpesviruses Epstein-Barr virus and cytomegalovirus are frequently detectable in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and could contribute to disease pathogenesis. With the goal of inhibiting herpesvirus replication, we tested the safety and tolerability of adding valganciclovir to standard IPF therapy (pirfenidone). We performed a single-center, Phase I, double-blind, randomized, placebo-controlled trial comparing valganciclovir 900 mg daily with placebo in patients with IPF with serologic evidence of prior Epstein-Barr virus and/or cytomegalovirus infection who were tolerating full-dose pirfenidone (2,403 mg/d). Subjects were randomized to valganciclovir or placebo 2:1 for 12 weeks of active treatment with off-treatment follow-up for up to 12 months. The primary safety endpoint was the number of subjects discontinuing the study drug before completing 12 weeks of treatment. Thirty-one subjects with IPF were randomized to valganciclovir ( = 20) or placebo ( = 11). All subjects completed assigned therapy except one subject in the valganciclovir group, who discontinued the study drug after developing a rash. The total number of adverse events was similar between study groups. In a prespecified analysis of secondary physiologic endpoints, we observed a trend toward improved forced vital capacity from randomization to Week 12 in valganciclovir-treated subjects (-10 ml; interquartile range [IQR], -65 to 70 ml) versus placebo-treated subjects (40 ml; IQR, -130 to 60 ml), which persisted through 12 months of follow-up. Valganciclovir is safe and well tolerated as an add-on therapy to pirfenidone in patients with IPF. Clinical trial registered with ClinicalTrials.gov (NCT02871401).
Topics: Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Idiopathic Pulmonary Fibrosis; Valganciclovir; Vital Capacity
PubMed: 33740394
DOI: 10.1513/AnnalsATS.202102-108OC -
American Journal of Transplantation :... Dec 2019
Topics: BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Valganciclovir; Viremia
PubMed: 31529778
DOI: 10.1111/ajt.15598 -
Transplant Infectious Disease : An... Feb 2022To evaluate the association of conversion from valganciclovir to letermovir on cytomegalovirus-specific cellular immunity.
Letermovir conversion after valganciclovir treatment in cytomegalovirus high-risk abdominal solid organ transplant recipients may promote development of cytomegalovirus-specific cell mediated immunity.
PURPOSE
To evaluate the association of conversion from valganciclovir to letermovir on cytomegalovirus-specific cellular immunity.
METHODS
Adult patients were included if they received a kidney or liver transplant between 8/1/2018-12/31/20, developed symptomatic, high-level CMV viremia and were converted to letermovir 480 mg daily as monotherapy after treatment with ganciclovir-derivatives for a minimum of 4 weeks and had subsequent CMV cell-mediated immunity (CMI) testing via ICS assay by flow cytometry (Viracor Eurofins T Cell Immunity Panel).
RESULTS
Seven patients met inclusion criteria; 87.5% were male and recipients of a kidney transplant. All patients were CMV high risk (D+/R-). Mean time from transplant to CMV disease was 200 ± 91 days. Peak viral load (VL) during CMV treatment was 540,341 ± 391,211 IU/mL. Patients received a mean of 30 ± 24 weeks (range: 4-78 weeks) of therapy with ganciclovir-derivatives at induction doses prior to letermovir introduction. The median absolute lymphocyte count (ALC) at letermovir initiation was 400/μL (IQR 575) and the median VL was 51.6 (range: ND-490) IU/mL. Most patients (n = 5/7, 71.4%) experienced an increase in VL 1 and/or 2 weeks after conversion to letermovir. All patients had positive CMI per ICS assay after conversion. Patients received a mean of 10.3 ± 6.9 weeks of letermovir prior to having a positive result. Median ALC at positivity was 900/μL. Immunosuppression was not further reduced from initiation of letermovir to demonstration of CMV CMI. No patient had progressive replication or breakthrough disease while maintained on letermovir and three patients (42.9%) underwent antiviral withdrawal without recurrence at the last follow-up.
CONCLUSION
In this case series of abdominal transplant recipients with severe or persistent CMV infection, patients developed CMV-specific CMI after conversion to letermovir monotherapy. These data suggest that using letermovir in place of valganciclovir for secondary prophylaxis may address the lack of efficacy previously seen with this approach, as well as the issues that plague antiviral withdrawal with systematic monitoring. Future prospective studies are needed to evaluate this effect in a more controlled research environment with serial CMI testing to elucidate the optimal duration of letermovir when used in this way.
Topics: Acetates; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Immunity, Cellular; Kidney Transplantation; Male; Quinazolines; Transplant Recipients; Valganciclovir
PubMed: 34799964
DOI: 10.1111/tid.13766 -
Clinical Infectious Diseases : An... Dec 2020Cytomegalovirus (CMV) is the most common congenital infection and infectious cause of fetal anomaly and neurologic injury. However, treatment strategies for congenital...
Cytomegalovirus (CMV) is the most common congenital infection and infectious cause of fetal anomaly and neurologic injury. However, treatment strategies for congenital CMV (cCMV) infection during pregnancy remain elusive. We report a case of hydrops fetalis secondary to cCMV infection with minimal sequelae after maternal and subsequent neonatal treatment with valganciclovir.
Topics: Cytomegalovirus; Cytomegalovirus Infections; Female; Fetal Diseases; Humans; Pregnancy; Pregnancy Complications, Infectious; Valganciclovir
PubMed: 32198512
DOI: 10.1093/cid/ciaa305 -
Transplantation Proceedings 2020Valganciclovir (VGCV) is used as prophylaxis against cytomegalovirus (CMV) infection after pediatric living donor liver transplantation (LDLT). The purpose of this study... (Clinical Trial)
Clinical Trial
OBJECTIVES
Valganciclovir (VGCV) is used as prophylaxis against cytomegalovirus (CMV) infection after pediatric living donor liver transplantation (LDLT). The purpose of this study was to examine the efficacy of 1 year of preemptive VGCV administration compared with a shorter administration after pediatric LDLT.
METHODS
VGCV was administered to 56 children who underwent LDLT. CMV and Epstein-Barr virus (EBV) antibody status, pp65 antigenemia, and other laboratory data were assessed at 1 year after LDLT. Patients were divided into the 1-year group (n = 32) (patients who had 1 year of VGCV administration) and the <1-year group (n = 24) (patients who had less than 1 year of VGCV administration).
RESULTS
Study participants consisted of 34 females and 22 males, with a mean age of 4.2 years at transplant. Regarding pretransplant donor (D)/recipient (R) CMV antibody status, 13 were D positive (+)/R negative (-), 27 were D+/R+, 8 were D-/R+, and 8 were D-/R-. For EBV, 22 were D+/R+, 32 were D+/R-, and 2 were D-/R-. In the 1-year group, only 2 patients (6.5%) developed CMV infection, whereas 8 patients (33.3%) developed CMV infection in the <1-year group. The CMV pp65 antigenemia assay was positive in 2 patients. CMV IgM was positive in 7 patients. One year of preemptive VGCV administration was associated with a lower incidence of CMV infection (P = .008), but not EBV infection. No adverse effects were observed.
CONCLUSIONS
One year of preemptive VGCV administration after LDLT is safe and suppresses CMV infection. It was useful after pediatric LDLT.
Topics: Adolescent; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunocompromised Host; Incidence; Liver Transplantation; Living Donors; Male; Time Factors; Valganciclovir
PubMed: 32571698
DOI: 10.1016/j.transproceed.2020.01.163