Ganciclovir Group Research Articles

2% Ganciclovir Controlled Posner-Schlossman Syndrome Relapse and Reduced the Chance of Corticosteroid Dependence: A Large Cohort in East China

ABSTRACT Purpose To present the process from acute Posner-Schlossman syndrome (PSS) relapse to remission under 2% ganciclovir (GCV), corticosteroids and anti-glaucoma agents on 323 patients. Methods A retrospective study enrolling 323 PSS patients. Demographics and ophthalmic examination results were generated. Patients were treated with GCV, corticosteroids and anti-glaucoma agents andfollowed up every 2–6 weeks. Results Patients were divided into the GCV monotherapy (N = 65, 20.12%), GCV and corticosteroids (G+C, N = 106) and GCV, corticosteroid and IOP-lowering drugs (G+C+L, N = 152) group. The G+C+L group had the highest intraocular pressure (IOP, 26.33 ± 10.26 mmHg, P < 0.001) and largest cup-to-disc ratio (0.58 ± 0.19, P < 0.05). After treatment, IOP of three groups dropped to similar level. Ninety-nine (30.65%) patients were corticosteroid-dependent whose daily corticosteroid consumption decreased after using GCV (from 2.23 ± 1.02 to 0.97 ± 0.98 drops/day). Conclusion 2% GCV solutions worked effectively on PSS relapse with corticosteroids and anti-glaucoma agents. In patients suspected of CMV infection, proper GCV could reduce the chance of corticosteroid dependence.

Abstract TP204: Elimination Of Senescent Cells Prevents The Development Of Intracranial Aneurysm Rupture In Mice

Introduction: Aging is one of the risk factors for intracranial aneurysm rupture. Aging causes various changes in cellular homeostasis, including cellular senescence. Cellular senescence is defined as a state of irreversible cellular growth arrest. Senescence cells secrete pro-inflammatory senescence-associated secretory phenotypes (SASPs). SASPs affect surrounding cells and contribute to a vicious cycle of senescence and induce inflammation. Recent studies strongly suggest that inflammation promotes aneurysm rupture. Therefore, the accumulation of senescence cells may induce aneurysm rupture due to pro-inflammatory effects of SASPs. We hypothesized that the elimination of senescence cells reduces the aneurysm rupture. To test our hypothesis we used p16-3MR mice. P16-3MR mouse is a transgenic mouse model, in which senescence cells can be eliminated by treatment of ganciclovir (GCV). In previous reports, the elimination of senescence cells by GCV in p16-3MR mice improved senescence-related diseases. In this study, we tested whether the elimination of senescence cells by GCV in p16-3MR mice reduces the intracranial aneurysm rupture rate. Methods: We induced intracranial aneurysms by combining systemic hypertension and a single injection of elastase into the cerebrospinal fluid in mice. We compared the vehicle to GCV group in p16-3MR aged male mice (10-15 months, vehicle vs GCV: 9 vs 6). We started GCV treatment the same day after aneurysm induction. Aneurysm rupture rate was used as the primary endpoint. Results: There was no statistical difference in the formation rate of aneurysms between the vehicle and the GCV group. However, the aneurysmal rupture rate was significantly lower in the senescence cell-depleted mice (P &lt; 0.05). Additionally, the symptom-free curve (Kaplan-Meier analysis curve) showed a significant reduction of aneurysm rupture in the GCV-treated group (P &lt; 0.05). Conclusions: The elimination of senescence cells reduced the aneurysm rupture rate in a mouse model of the aneurysm. Our results suggest that the accumulation of senescence cells induces aneurysm rupture. Therefore, the pharmacological prevention of the accumulation of senescence cells may be a new therapeutic target in aneurysm rupture.

Comparative Efficacy of Topical Ophthalmic Ganciclovir and Oral Famciclovir in Cats with Experimental Ocular Feline Herpesvirus-1 Epithelial Infection.

Purpose: To determine the comparative efficacy of ganciclovir ophthalmic gel and famciclovir oral tablets in cats with experimentally induced ocular feline herpesvirus-1 (FHV-1) epithelial infection. Methods: A randomized, placebo-controlled trial was performed using 16 nonvaccinated, specific pathogen-free cats with experimental FHV-1 infection induced by topical ocular inoculation. Cats received topical ganciclovir 0.15% ophthalmic gel (1 drop 3 times daily, n = 6 cats), oral famciclovir (90 mg/kg twice daily, n = 6), or topical artificial tear gel (1 drop 3 times daily, n = 4) for 14 days. Cats were monitored after inoculation for 30 days. Ophthalmic examinations were performed every 2 days and ocular disease scores calculated. In vivo confocal microscopy was performed, and corneal leukocyte infiltrates quantified. Ocular samples for FHV-1 quantitative polymerase chain reaction (qPCR) and virus isolation assays were collected every 3 days. Hemograms and serum biochemistry panels were performed at intervals. Results: Clinical ocular disease scores and corneal leukocyte infiltrates were significantly lower in the ganciclovir and famciclovir groups compared with placebo, but no significant differences were detected between the antiviral treatment groups. Ocular viral loads determined by qPCR were significantly lower in the ganciclovir group compared with the placebo group, but there were no significant differences between the other study groups. Hemograms and biochemistry panels were unremarkable. Conclusion: Topical application of ganciclovir gel 3 times daily was well-tolerated and displayed similar efficacy at reducing clinical ocular disease scores and corneal inflammation as twice daily oral famciclovir treatment in cats with experimental ocular FHV-1 infection.

Reliable quantification of Cytomegalovirus DNAemia in Letermovir treated patients

Polymerase chain reaction (PCR) based methods are a fast and sensitive approach to detect and monitor viral load in Cytomegalovirus (CMV) patients. Letermovir (LMV) acts at a late stage during the CMV replication cycle and does not inhibit CMV DNA replication per se. Therefore, quantitative nucleic acid amplification testing might lead to the overestimation of viral load in patients treated with LMV and underestimate treatment success. To study this discrepancy, we treated infected cells with LMV or Ganciclovir (GCV) and compared viral progeny DNA levels. Prior to nucleic acid extraction and qPCR measurements we pretreated cell lysates and cell culture supernatants from infected cells with DNase I. This step assumes the degradation of DNA which is not protected from a viral capsid. LMV treatment did not reduce genomic copies (GC) in samples from whole cell lysates compared to samples treated with GCV. DNase treatment prior to DNA extraction, decreased GC in the LMV treated group to comparable levels as seen in the GCV group. In cell culture supernatants, LMV or GCV treatment led to an equivalent reduction of CMV GC. In this case, DNase treatment exerted a negligible effect on both groups. We conclude that the accumulation of concatemeric DNA within cells seems to be a confounding variable when monitoring LMV efficacy via qPCR. However, qPCR shows to be a reliable method to evaluate antiviral efficacy of LMV in cell free specimens. These results have strong clinical implications for the monitoring of CMV therapy during LMV treatment.

Difference between Acyclovir and Ganciclovir in the Treatment of Children with Epstein-Barr Virus-Associated Infectious Mononucleosis.

Objective To investigate the efficacy differences between acyclovir and ganciclovir in the treatment of children with Epstein–Barr virus (EBV)- associated infectious mononucleosis (IM). Methods A total of 128 children with EBV-IM who were admitted to our hospital from February 2019 to February 2021 were selected and randomly divided into the acyclovir group (n = 64) and the ganciclovir group (n = 64) according to the random number table method. All the children were given symptomatic treatments such as protecting the liver and reducing fever. On this basis, the acyclovir group was given an intravenous drip of acyclovir, while the ganciclovir group was given an intravenous drip of ganciclovir. The treatment was continued for 7 days. After the treatment, the clinical efficacy, disappearance time of symptoms and signs, related blood routine indexes, EBV-DNA negative conversion rate, and the incidence of adverse reactions during the treatment were compared between the two groups. Results After treatment, the total effective rate of the ganciclovir group (92.19%) was higher than that of the acyclovir group (73.44%) and the difference was statistically significant (P < 0.05). The disappearance time for the symptoms and signs of angina, fever, lymphadenopathy, hepatomegaly, and splenomegaly in the ganciclovir group was lower than that in the acyclovir group, and the difference was statistically significant (P < 0.05). After treatment, the levels of atypical lymphocyte proportion, lymphocyte proportion, and WBC count in the two groups were lower than those before treatment, the levels in the ganciclovir group were lower than those in the acyclovir group, and the difference was statistically significant (P < 0.05). After treatment, the EBV-DNA negative conversion rate (81.25%) in the ganciclovir group was higher than that in the acyclovir group (60.93%) and the difference was statistically significant (P < 0.05). During treatment, the incidence of adverse reactions in the ganciclovir group was significantly lower than that in the acyclovir group and the difference was statistically significant (P < 0.05). Conclusion In the treatment of children with EBV-IM, the therapeutic effect of ganciclovir is obviously superior to that of acyclovir. Ganciclovir can quickly eliminate the symptoms of angina, fever, enlarged lymph nodes, and other signs in children, can improve abnormal blood indicators, and has a higher negative conversion rate of EBV and less adverse reactions.

Clinical characteristics and effectiveness of antiviral agents in hospitalized children with infectious mononucleosis in China: A multicenter retrospective study.

ABSTRACTImportanceThe clinical characteristics of infectious mononucleosis (IM) in Chinese children have not been evaluated in multicenter studies, and the effectiveness of antiviral treatment are controversial.ObjectiveTo investigate the clinical characteristics of Chinese children with IM and current status of antiviral therapy for affected patients.MethodsHospitalized patients with IM were enrolled between 2018 and 2020 in five children’s hospitals in China. The clinical characteristics were compared among four age groups: <3 years, 3–<6 years, 6–<10 years, and ≥10 years. The clinical characteristics of IM and effectiveness of antiviral therapy were compared among patients receiving acyclovir (ACV), ganciclovir (GCV), and no antiviral therapy (i.e., non‐antiviral group).ResultsIn total, 499 patients were analyzed; most patients were 3–<6 years of age. The most common symptoms and signs included fever (100%), lymphadenopathy (98.6%), pharyngitis (86.4%), eyelid edema (76.8%), and snoring (72.9%). There were significant differences in rash, hepatomegaly, and liver dysfunction among the four age groups. Patients aged < 3 years had a lower incidence of liver dysfunction and a higher incidence of rash. Among the 499 patients, 50.1% were treated with GCV, 26.3% were treated with ACV, and 23.6% received no antiviral therapy. Compared with the non‐antiviral group, patients in the ACV and GCV groups had longer durations of fever (P < 0.001). There were no significant differences in the incidences of complications among the three treatment groups.InterpretationThe incidence of IM in Chinese children peaked at 3–<6 years of age. Clinical features of IM varied according to age. Patients receiving antiviral therapy exhibited more serious clinical manifestations than did patients without antiviral therapy. The effectiveness of antiviral therapy for IM requires further analysis.

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation

BackgroundThe effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation.MethodsThis double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37).ResultsThe primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0–51] and 0 [0–43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups.ConclusionsIn patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.

Comparison of Transplantation Outcomes after Foscarnet and Ganciclovir Administration as First-Line Anti-Cytomegalovirus Preemptive Therapy

Ganciclovir (GCV) and foscarnet (FCN) are effective anti-cytomegalovirus (CMV) preemptive therapies; however, the impact of the 2 agents on various clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) remains unclear. We retrospectively analyzed data on 532 patients undergoing allogeneic HSCT from unrelated donors and administered FCN (n=86) or GCV (n=446) as first-line anti-CMV preemptive therapy. Overall survival, relapse, and nonrelapse mortality (NRM) did not differ between the FCN and GCV groups, whereas the GCV group had a higher risk of chronic graft-versus-host disease (cGVHD) (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.28 to 4.39; P=.006) and extensive cGVHD (HR, 3.94; 95% CI, 1.43 to 10.9; P=.008). All 13 patients with cGVHD in the FCN group survived. Switching to the other agent was done mainly due to hematologic adverse events in the GCV group and mainly due to insufficient efficacy in the FCN group. The incidence of end-organ CMV disease was similar in the 2 groups. Selection of FCN or GCV as first-line preemptive anti-CMV therapy did not affect survival, relapse, or NRM. Physicians can select either of the agents, depending on the clinical situation; however, the selection may influence the cGVHD-related clinical course in HSCT recipients.

Prevention of cytomegalovirus infection after solid organ transplantation: a Bayesian network analysis

BackgroundCytomegalovirus infection is one of the most common complications after solid organ transplantation. There have been several classes of antiviral drugs for the prevention of cytomegalovirus infection, such as acyclovir, valacyclovir, ganciclovir and valganciclovir.MethodsWe searched relevant prospective and multi-armed studies on PubMed from Jan. 1984 up to Mar. 2018.ResultsSeventeen prospective studies involving 2062 patients were included in the analysis. In the case of cytomegalovirus infection, the ganciclovir group (OR = 0.24, 95% CI 0.09–0.57) and the valacyclovir group (OR = 0.20, 95% CI 0.04–0.69) provided significantly better outcomes than the control group. The ganciclovir (OR = 0.37, 95% CI 0.13–0.86) and valacyclovir groups (OR = 0.31, 95% CI 0.07–0.98) showed moderate superiority compared to the acyclovir group. As for cytomegalovirus disease, the ganciclovir, valacyclovir and valganciclovir groups showed significant advantages compared with the control group (ganciclovir group: OR = 0.17, 95% CI 0.07–0.31, valacyclovir group: OR = 0.08, 95% CI 0.01–0.33, valganciclovir group: OR = 0.14, 95% CI 0.02–0.45). Similarly, the ganciclovir group (OR = 0.38, 95% CI 0.12–0.71) and the valacyclovir group (OR = 0.17, 95% CI 0.03–0.72) showed better results than the acyclovir group.ConclusionValacyclovir showed to be the most efficient antiviral for the prevention of cytomegalovirus infection and disease. Additional studies are required to evaluate putative side effects associated with valacyclovir administration.

In vivo efficacy of ganciclovir by using single-walled carbon nanotubes as a drug carrier against infectious spleen and kidney necrosis virus in mandarin fish

Infectious spleen and kidney necrosis virus (ISKNV) cause a high mortality disease which leads to a significant economic loss on mandarin fish in China. At present, there is no effective drug against this fatal disease because of several impenetrable barriers (cell, skin and gastrointestinal tract). In this study, we selected ganciclovir for the treatment of ISKNV and choose single-walled carbon nanotubes (SWCNTs) as ganciclovir carrier by immersion bath on mandarin fish infected with ISKNV. After 7 d post-infection, cumulative mortality was 14.75% and infection rate was 26.55% in naked ganciclovir group (40 mg/L). Meanwhile, cumulative mortality of 32.50% and infection rate of 15.30% were observed in G-SWCNTs group (20 mg/L). In the control group, cumulative mortality was 88.75% and the infection rate was 100%. At 6 h post-infection, the concentration of ganciclovir was detected to be 34.58 μg/g in naked ganciclovir group (20 mg/L). And in G-SWCNTs groups (10 mg/L) at 6 h, the concentration of ganciclovir was 39.35 μg/g. Besides, the time detention of ganciclovir in G-SWCNTs group was significantly extended compared with the naked ganciclovir group in the same dosage. Moreover, enzyme activities, complement (C3) content and immune-related genes expression were used to verify the enhancement effect induced in G-SWCNTs groups, herein all these mentioned activities reached the highest level at 3 days post-treatment. The results showed that ganciclovir-SWCNTs can be a plausible candidate for preventing and controlling ISKNV among farmed mandarin fish.

Treatment outcomes of reduced-dose intravitreal ganciclovir for acquired immunodeficiency syndrome patients with cytomegalovirus retinitis

Objective To evaluate the efficacy and safety of reduced-dose intravitreal ganciclovir for the treatment of acquired immunodeficiency syndrome (AIDS) patients with cytomegalovirus retinitis (CMVR). Methods A prospective observational cohort study observed 15 AIDS patients (28 eyes) who suffered from CMVR onset between January 2016 and December 2018 at Nanning Aier Eye Hospital. Among this 28 eyes, BCVA of 6 eyes (21.4%) were between moving hand to counting finger, 15 eyes (53.6%) were between 0.02 to 0.1 and 7 eyes were better than 0.1 (25.0%). All eyes received intravitreal injection 0.1 ml of ganciclovir at 4 mg/ml (contain ganciclovir 0.4 mg). The induction regimen was twice weekly for 2 weeks and a maintenance period of the same dose weekly. The mean number of injections was 7.1±1.7 times. For hospitalized patients who had no contraindicated received a 14-day twice daily intravenous ganciclovir (IVG) 5.0 mg/kg·d until complete resolution of CMVR. All patients were divided into intravitreal ganciclovir (IVTG) group and IVTG+IVG group according to different treatment plans, which were 5 cases with 8 eyes and 10 cases with 20 eyes, respectively. The follow-up was more than 6 months. BCVA, complete resolution or stable of the lesion and complications were observed. Results Six months later, 20 eyes (71.4%) had a obvious reduced or disappeared of the anterior chamber and vitreous inflammation, and the retinal lesions became stable or complete resolution. 24 eyes showed improvements of BCVA and 4 eyes showed stable. 2 eyes (7.1%) presented with BCVA ≤ counting finger, 7 eyes (25.0%) were 0.02- 0.1 and 19 eyes were ≥ 0.1 (67.9%). Compared with before treatment, the ratio of BCVA that less than or equal to counting finger and between 0.02 to 0.1 decreased(21.4% vs 7.1% and 53.6% vs 25.0%, respectively), but the ratio of BCVA better than 0.1 increased (25.0% vs 67.9%). When IVTG+IVG group was compared with IVTG group, the average time-to-resolution of CMVR were 83.2±25.2 and 85.3±24.4 days respectively. There was no significant difference in resolution times(Z=0.17, P=0.87). The ratio of retinal lesions became stable or complete resolution were 75.0% (15 eyes) and 62.5% (5 eyes), there was no evident difference in time-to-resolution between the two groups (F=0.42, P=0.51). No recurrence was seen during the follow-up period. In cases of unilateral CMVR, there were no patients with a second eye involvement during the follow-up period. No endophthalmitis, vitreous hemorrhage, retinal detachment were found in our study. Conclusion Reduced-dose intravitreal ganciclovir is a safe and effective treatment option for CMVR. Key words: Acquired immunodeficiency syndrome/complications; Cytomegalovirus retinitis/drug therapy; Ganciclovir/therapeutic use; Treatment outcome

Impact of the patient's body weight on the efficacy and adverse events of valganciclovir for cytomegalovirus reactivation after hematopoietic stem cell transplantation.

While the dose of ganciclovir (GCV) is decided base on patients' body weight (BW), that of valganciclovir (VGCV) is fixed as 900 or 1800mg/d regardless of the patient's BW in preemptive therapy for cytomegalovirus (CMV) reactivation in hematopoietic stem cell transplantation. We analyzed the impact of the patient's BW on the effectiveness and adverse events (AEs) of VGCV. From March 2004 to February 2017, 27 patients received VGCV as a first-line treatment for CMV reactivation. As a historical control group, we extracted 17 patients who started to receive GCV at a similar timing. We used the following definitions of outcomes: speed of reduction of CMV antigenemia (CMV-AG) as a measure of effectiveness, ratios of baseline and minimum value for white blood cell (WBC) and platelet counts, and ratio of baseline and maximum values for serum creatinine (sCr) as measures of AEs. As a result, there was no significant correlation between average daily dose of VGCV with or without adjusting for the patient's BW and speed of reduction of CMV-AG. On the other hand, the decreases in WBC and platelets and the increase in sCr were significantly correlated with the cumulative dose of VGCV. However, the absolute values of the correlation coefficients did not increase when we analyzed the correlations between the BW-adjusted cumulative dose of VGCV and factors associated with adverse events. There were no significant differences in efficacies or AE parameters between the GCV and VGCV groups.In conclusion, the patient's BW did not significantly affect the effectiveness or adverse events of VGCV.

CMV Viral Load Kinetics as Surrogate Endpoints for Antiviral Prophylaxis Trials

<h3>Introduction</h3> The paradigm for preventing clinically significant cytomegalovirus (CMV) infection and CMV disease after hematopoietic cell transplantation (HCT) has shifted from preemptive treatment to antiviral prophylaxis with the approval of letermovir. Previously, our group validated the use of quantitative CMV DNA viral load as a surrogate endpoint for tissue-invasive CMV disease (ASBMT 2018) in the <i>pre-emptive treatment setting</i>. <h3>Objectives</h3> To address whether CMV viral load kinetics could serve as valid surrogate endpoints for CMV disease in the <i>prophylactic setting</i>, we performed CMV viral load testing of frozen serum samples collected during a placebo-controlled randomized trial of ganciclovir (GCV) given at engraftment (Goodrich et al. Ann Intern Med 1993). Because this study pre-dated the approval of ganciclovir, CMV disease occurred in an extremely high proportion of patients, allowing us to link viral load kinetics with CMV disease, which would not be possible in the modern treatment environment. <h3>Methods</h3> We calculated each patient's CMV viral load kinetics (mean, peak, maximum change, percentage of positive viral loads) from samples collected during the first five weeks after randomization and analyzed their value as surrogates for CMV disease by 24 weeks after randomization. First, we tested each marker for fulfillment of the Prentice criteria for valid surrogate endpoints using multivariable logistic regression, including quantifying the degree to which each marker captured the effect of ganciclovir on CMV disease. Secondly, to determine the ability of the viral load markers to predict CMV disease, we developed a ‘SuperLearner' machine learning model and quantified prediction accuracy by cross-validated area under the receiver-operator characteristic curves (cv-AUCs). <h3>Results</h3> Mean, peak, change, and percentage of positive viral loads were significantly higher in the placebo group than in the ganciclovir group. See viral loads by group in Fig 1. Percentage of positive viral load satisfied Prentice criteria as a valid surrogate endpoint for CMV disease by week 24 after randomization (Fig 2). All kinetics explained greater than 80% of ganciclovir's reduction in CMV disease (mean: 86%, peak: 83%, maximum change: 95%, percent positive: 94%). We found that a SuperLearner model that included all four viral load kinetics, CMV donor serostatus, acute graft-versus-host disease, and baseline viral load predicted CMV disease with 91% cv-AUC in the placebo group, 78% in the ganciclovir group, and 82% in the combined groups (Fig 3). <h3>Conclusion</h3> We have shown for the first time in a clinical endpoint-rich, placebo-controlled antiviral prophylaxis trial that CMV viral load kinetics fulfill the Prentice criteria as valid surrogate endpoints and have high predictive value for CMV disease after HCT.

Efficacy of Valganciclovir Versus Ganciclovir in Treatment of Symptomatic Cytomegalovirus Infection in Infants: An Open- Labeled Randomized Controlled Trial

Introduction: Congenital cytomegalovirus (CMV) infection is the most common viral infection transmitted via the placenta, causing significant neurodevelopmental impairment in infants and children. Gancyclovir and Valgancyclovir are two drugs used in the treatment of symptomatic CMV infected case which have limited comparative study. This study compared the efficacy and tolerability of these two drugs on symptomatic CMV infected infants.Methodology: This was an open-label randomized controlled trial done to compare oral valganciclovir(VGCV) with injectable ganciclovir (GCV) in the treatment of symptomatic congenital CMV infected infants. A total of 72 patients were included; 12 patients discontinued the treatment due to noncompliance or side effects. Pre and post-treatment CMV virus levels and adverse effects were monitored. Psychological, visual, and hearing assessments were performed at baseline and six months post-treatment.Results: The mean age of the infants in VGCV and GCV group was 7.10±3.58 and 7.50±3.99 months, respectively. Nineteen infants presented with developmental delay, 13 with seizure, 4 with a movement disorder. Twenty-one percent of the infants were preterm, and 38% were low birth weight. Eighteen infants had a neonatal seizure. Twenty-eight infants of VGCV and 24 infants of the GCV group showed clearance of the virus after six weeks of treatment. No statistical difference was found in virus clearance. Regarding ophthalmological assessment, infants had chorioretinitis, optic atrophy, squint, and cortical blindness. On hearing assessment, none of the infants deteriorated after drug administration, while some showed improved hearing. None of the infants showed deterioration of cognition, while some of the infants showedimprovement in cognitive assessment, but there was no significant difference in two groups. The side effects of GCV were significantly greater than VGCV (P&lt;0.05). Conclusion: In symptomatic congenital CMV infection in infants, VGCV is as efficient as GCV, and the former has fewer side effects.

Cost analysis of ganciclovir and foscarnet in recipients of allogeneic hematopoietic cell transplant with cytomegalovirus viremia.

Ganciclovir (GCV) and foscarnet (FOS) are the most commonly used antivirals for preemptive treatment of cytomegalovirus (CMV) viremia in recipients of allogeneic hematopoietic cell transplantation (alloHCT). The current literature indicates similar efficacy between these agents. Thus, the primary consideration for choice of initial anti-CMV treatment is the safety profile, time period after alloHCT, and concern of myelosuppression or renal dysfunction. Herein, we retrospectively reviewed medical records of 124 alloHCT recipients who received GCV or FOS between April 27, 2014, and December 31, 2015, during the first year post-transplant. Healthcare resource use included drug, hospitalization, home health, dialysis, and growth factor costs. Total duration of therapy was longer in the GCV group (37days vs 28days, P=.21) but hospitalization days were similar (9days) in both groups. The total treatment cost was significantly lower in the GCV group ($38100 vs $59400, P<.05). Preemptive anti-CMV therapy is associated with major healthcare resource costs, which were greater in patients who required FOS than those who were treated with GCV.

Prevention and Treatment of Cytomegalovirus after Solid Organ Transplantation: A Bayesian Network Analysis

Cytomegalovirus (CMV) infection is one of the most common complications after solid organ transplantation. Clinically, there have been several kinds of antiviral drugs for the prevention and treatment of CMV, such as acyclovir, valacyclovir, ganciclovir and valganciclovir. In order to evaluate the efficacy and safety of these antiviral drugs, we performed a Bayesian network meta-analysis. We searched relevant prospective and multi-armed studies on PubMed up to Mar.2018. The primary outcome is the occurrence of CMV infection and CMV disease after solid organ transplantation. Finally, 17 prospective studies involving 2062 patients were included in our analysis. In the case of CMV infection, the ganciclovir group (OR= 0.24 95% CI: 0.09-0.57) and the valacyclovir group (OR=0.20 95% CI: 0.04-0.69) is significantly better than the control group. The ganciclovir (OR=0.37 95% CI: 0.13-0.86) and valacyclovir groups (OR=0.31 95% CI: 0.07-0.98) showed moderate superiority compared to the acyclovir group. As for CMV disease, the ganciclovir group, the valacyclovir group and the valganciclovir group showed significant advantages compared with the control group (ganciclovir group: OR=0.17 95% CI: 0.07-0.31, valacyclovir group: OR=0.08 95% CI: 0.01-0.33, valganciclovir group: OR=0.14 95% CI: 0.02-0.45). Similarly, the ganciclovir group (OR=0.38 95% CI: 0.12-0.71) and the valacyclovir group (OR=0.17 95% CI: 0.03-0.72) is better than the acyclovir group. In our conclusion, valacyclovir might be the most efficient in the prevention and treatment of CMV infection and disease. However, it is also likely to induce leukopenia. Acyclovir may have the weakest therapeutic effect, while the possibility of leukopenia is also minimal. In order to achieve better effect, doctors should consider the clinical situation of every patient before clinical selection of antiviral drugs. Funding: None. Declaration of Interest: We declare no competing interests.

Evaluation of topical ophthalmic ganciclovir gel for the treatment of dogs with experimentally induced ocular canine herpesvirus-1 infection.

OBJECTIVE To determine the in vitro half maximal effective concentration (EC50) of ganciclovir for canine herpesvirus-1 (CHV-1) and to evaluate the efficacy of ganciclovir ophthalmic gel in dogs with experimentally induced ocular CHV-1 infection. ANIMALS 10 specific pathogen-free adult Beagles. PROCEDURES Cytotoxicity and EC50 of ganciclovir for CHV-1 were determined during in vitro experiments. During an in vivo experiment, dogs with experimentally induced ocular CHV-1 infections received 1 drop of 0.15% ganciclovir (ganciclovir group; n = 5) or artificial tear (control group; 5) ophthalmic gel in both eyes 5 times daily for 7 days, then 3 times daily for 7 days. For each dog, ophthalmic and confocal microscopic examinations were performed at predetermined times to determine severity of ocular disease and inflammation. Conjunctival swab specimens were collected at predetermined times for PCR assay analysis to determine CHV-1 shedding. RESULTS No in vitro cytotoxic effects were observed for ganciclovir concentrations ≤ 500μM. The EC50 of ganciclovir for CHV-1 was 37.7μM. No adverse effects associated with ganciclovir were observed during the in vivo experiment. Mean ocular disease and inflammation scores for the ganciclovir group were significantly lower than those for the control group. Mean duration of CHV-1 shedding for the ganciclovir group (0.4 days) was significantly shorter than that for the control group (6.2 days). CONCLUSIONS AND CLINICAL RELEVANCE Topical administration of 0.15% ganciclovir ophthalmic gel was well tolerated and effective in decreasing clinical disease scores, ocular tissue inflammation, and duration of viral shedding in dogs with experimentally induced ocular CHV-1 infection.

Effect of Ganciclovir on IL-6 Levels Among Cytomegalovirus-Seropositive Adults With Critical Illness

The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown. To determine whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill. Double-blind, placebo-controlled, randomized clinical trial (conducted March 10, 2011-April 29, 2016) with a follow-up of 180 days (November 10, 2016) that included 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure at 14 university intensive care units (ICUs) across the United States. Patients were randomized (1:1) to receive either intravenous ganciclovir (5 mg/kg twice daily for 5 days), followed by either intravenous ganciclovir or oral valganciclovir once daily until hospital discharge (n = 84) or to receive matching placebo (n = 76). The primary outcome was change in IL-6 level from day 1 to 14. Secondary outcomes were incidence of CMV reactivation in plasma, mechanical ventilation days, incidence of secondary bacteremia or fungemia, ICU length of stay, mortality, and ventilator-free days (VFDs) at 28 days. Among 160 randomized patients (mean age, 57 years; women, 43%), 156 patients received 1or more dose(s) of study medication, and 132 patients (85%) completed the study. The mean change in plasma IL-6 levels between groups was -0.79 log10 units (-2.06 to 0.48) in the ganciclovir group and -0.79 log10 units (-2.14 to 0.56) in the placebo group (point estimate of difference, 0 [95% CI, -0.3 to 0.3]; P > .99). Among secondary outcomes, CMV reactivation in plasma was significantly lower in the ganciclovir group (12% [10 of 84 patients] vs 39% [28 of 72 patients]); absolute risk difference, -27 (95% CI, -40 to -14), P < .001. The ganciclovir group had more median VFDs in both the intention-to-treat (ITT) group and in the prespecified sepsis subgroup (ITT group: 23 days in ganciclovir group vs 20 days in the placebo group, P = .05; sepsis subgroup, 23 days in the ganciclovir group vs 20 days in the placebo group, P = .03). There were no significant differences between the ganciclovir and placebo groups in duration of mechanical ventilation (5 days for the ganciclovir group vs 6 days for the placebo group, P = .16), incidence of secondary bacteremia or fungemia (15% for the ganciclovir group vs 15% for the placebo group, P = .67), ICU length of stay (8 days for the ganciclovir group vs 8 days for the placebo group, P = .76), or mortality (12% for the ganciclovir group vs 15% for the placebo group, P = .54). Among CMV-seropositive adults with critical illness due to sepsis or trauma, ganciclovir did not reduce IL-6 levels and the current study does not support routine clinical use of ganciclovir as a prophylactic agent in patients with sepsis. Additional research is necessary to determine the clinical efficacy and safety of CMV suppression in this setting. clinicaltrials.gov Identifier: NCT01335932.

Oral Valganciclovir as Preemptive Therapy for Cytomegalovirus Reactivation in Pediatric Hematopoietic Stem Cell Transplant Patients.

Cytomegalovirus (CMV) infection is one of the most common complications after allogeneic hematopoietic stem cell transplantations (HSCT). Valganciclovir (VGC) has increasingly been used as prophylaxis against CMV infection after solid organ transplantation, but data on the efficacy and safety of VGC in pediatric HSCT patients are limited. We present our experience with VGC following ganciclovir (GCV) as preemptive therapy in pediatric HSCT patients. A total of 46 patients (38% patients) were found to be positive for CMV reactivation. Patients were treated with GCV (group I, n: 22) or GCV followed by VGC (GCV+VGC, group II, n: 24). VGC was preferred in the treatment of outpatients, whereas inpatients were treated with GCV. There was no significant difference in CMV clearance (P=0.78), treatment duration (P=0.087), and second CMV infection (P=0.3) between the 2 groups. The length of hospital stay was 21 days in GCV group, 14 days in VGC following GCV group (P=0.07). There were no treatment-related side effect in both groups. In conclusion, oral administration of VGC as preemptive therapy was found to be safe and effective. It is also a more suitable application for pediatric patients instead of an intravenous route. It could reduce the duration of inpatient stay and cost of hospitalization.

Clinical efficacy of oral ganciclovir for prophylaxis and treatment of recurrent herpes simplex keratitis.

Background:Herpes simplex keratitis (HSK) caused by herpes simplex virus 1 (HSV-1), which has high recurrent rate and incidence of severe vision loss, is the leading cause of infectious blindness in the world. The aim was to explore the clinical efficacy of oral ganciclovir (GCV) in the prevention of recurrent HSK.Methods:A multicenter, prospective, randomized, single-blind, and controlled clinical trial was conducted from April 2010 to June 2013. One hundred seventy-three patients (173 eyes involved) who were diagnosed as recurrent HSK definitely, including stromal keratitis and corneal endotheliitis, were divided into three groups randomly: negative control (placebo) group was topically administered with 0.15% GCV ophthalmic gel, 4 times per day and 0.1% fluorometholone eye drops, 3 times per day until resolution of HSK; positive control acyclovir (ACV) group was topically adopted the same ophthalmic gel and eye drops and additionally received oral ACV 400 mg 5 times a day for 10 weeks and followed by 400 mg 2 times per day for 6 months; test GCV group was topically adopted the same treatment as negative control group and additionally received oral GCV 1000 mg 3 times per day for 8 weeks. The symptoms and signs were evaluated before and after the therapy 1st week, 2nd week and then followed up every 2 weeks until recovery. Furthermore, we followed up recurrence of HSK for every 3 months after recovery and then assessed the cure time, recurrent rate and adverse reactions.Results:One hundred and seventy-three patients were followed up 7–48 months (mean 32.1 ± 12.3 months), but 34 patients were failed to follow-up. The cure time was 12.1 ± 4.3, 11.9 ± 4.0 weeks in negative control (placebo) group and positive control ACV group respectively (P = 0.991), which was longer than that in test GCV group (8.6 ± 2.8 weeks) and there was a significant difference between test GCV group and negative control (placebo) group or positive control ACV group (P = 0.000). Furthermore, the recurrent rate was higher in negative control (placebo) group (47.3%) than that in positive control group ACV (26.7%) and test GCV group (17.2%), and there was a great significant difference among the three groups (P = 0.007), but there was no significant difference between positive control ACV group and test GCV group (P = 0.358). In addition, there was no obvious adverse reaction expect neutropenia (only one patient in test GCV group).Conclusion:Short-term oral GCV could cure recurrent HSK and endotheliitis, shorten the course, reduce recurrent rate of HSK and have confirmed safety.