valganciclovir and Viremia

Cytomegalovirus (CMV) poses a significant threat to solid organ transplant recipients (SOTR). The incidence of CMV disease in SOTR varies according to immunosuppressive therapy, antiviral prophylaxis, donor and recipient serologic compatibility, and the transplanted organ: 9% to 23%, 22% to 29% and 8% to 32% after heart, liver and kidney transplant, respectively. CMV retinitis (CMVR) is a rare manifestation of CMV with a high risk of blindness. Infection may vary in severity, from initially clinically silent cases to full-blown advanced changes involving the eye. The most characteristic effects are changes in the retina, which usually begin at the retina's periphery and are asymptomatic, then these changes spread toward the center as the disease progresses and impairs vision. We describe CMV vitritis and retinitis in a 74-year-old patient after heart transplantation conducted in 1992. The first symptom of the disease was low vision in the left eye. Initially no blood viremia was observed; then the CMV viral load in the blood and vitreous body of the right eye was 2454 and 26 million IU/mL.Despite the initiation of treatment (intravitreal and then intravenous ganciclovir), the inflammatory process progressed rapidly and vision in the left eye was lost, although functional visual acuity in the right eye was maintained. Systemic antiviral therapy with intravenous ganciclovir lasted 6 weeks until the eradication of CMV viremia. The patient was on prophylactic therapy with oral valganciclovir for 12 months. A clinically silent course of CMVR delays diagnosis and therapy. Therefore, it is recommended that all SOTR undergo periodic ophthalmologic control to avoid delayed diagnosis.

Topics: Aged; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Retinitis; Ganciclovir; Heart Transplantation; Humans; Valganciclovir; Viremia

Cytomegalovirus (CMV) retinitis is typically diagnosed in patient with AIDS and those who underwent allogeneic hematopoietic cell transplant. However, it may develop in patients with acute lymphoblastic leukemia (ALL) who have not undergone hematopoietic cell transplantation. To increase awareness of CMV retinitis in this group, we describe 3 patients ages 3, 9, and 12, with ALL who developed CMV retinitis. The diagnosis of CMV retinitis was made on the basis of ophthalmological findings suggesting typical retinal lesions. In 2 cases, CMV DNAemia was present, while in 1 patient CMV DNA was detected only in vitreous fluid using the PCR technique. All cases were treated with intravenous ganciclovir for 2 or 3 weeks as induction therapy, followed by oral valganciclovir prophylaxis. Initially, active retinitis lesions resolved in all cases; however, in 1 patient CMV retinitis relapsed 3 times during follow-up. In this case, by using foscarnet therapy, satisfactory responses were achieved and the progression of CMV retinitis lesions stopped and eventually regressed.

Topics: Administration, Intravenous; Administration, Oral; Adolescent; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus Retinitis; DNA, Viral; Eye; Foscarnet; Ganciclovir; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Valganciclovir; Viremia; Vitreous Body

Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). This pilot prospective randomized clinical trial compares valganciclovir (VGV) to ganciclovir (GCV) as pre-emptive therapy for CMV viremia in the post-allogeneic HSCT population.. Patients undergoing allogeneic HSCT who were at risk for CMV viremia were monitored post HSCT by weekly quantitative whole blood polymerase chain reaction. Pre-emptive therapy was delayed until the viral load (VL) was >10,000 copies/mL once, or >5000 copies/mL twice. Patients were randomized to either GCV 5 mg/kg twice a day (b.i.d.) for 7 days followed by daily GCV 5 mg/kg for up to 21 days, or VGV 900 mg b.i.d. for 7 days followed by 900 mg daily for up to 21 days. The primary endpoint was clearance of viremia (VL <5000 copies/mL) within 28 days of initiation of therapy.. In total, 37 patients were enrolled; 19 patients received treatment with VGV and 18 patients received treatment with GCV. The VGV was not inferior in efficacy to GCV as pre-emptive therapy, with rates of viral clearance at 28 days of 89.5% and 83%, respectively (P-value for non-inferiority = 0.030). Toxicities were similar between the 2 arms. No patients developed CMV disease.. In this trial, the rates of clearance of viremia appear to be similar with VGV and GCV.

Topics: Administration, Oral; Adolescent; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Pilot Projects; Polymerase Chain Reaction; Prospective Studies; Transplantation, Homologous; Valganciclovir; Viral Load; Viremia; Young Adult

Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase.. In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16.. 352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference [95% confidence interval (CI)]: 32.8% [22.80-42.74]; P < .001) and key secondary endpoint (18.7% vs 10.3%; adjusted difference [95% CI]: 9.5% [2.02-16.88]; P = .01). Rates of treatment-emergent adverse events (TEAEs) were similar between groups (maribavir, 97.4%; IAT, 91.4%). Maribavir was associated with less acute kidney injury versus foscarnet (8.5% vs 21.3%) and neutropenia versus valganciclovir/ganciclovir (9.4% vs 33.9%). Fewer patients discontinued treatment due to TEAEs with maribavir (13.2%) than IAT (31.9%). One patient per group had fatal treatment-related TEAEs.. Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT. Clinical Trials Registration. NCT02931539 (SOLSTICE).

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Dichlororibofuranosylbenzimidazole; Drug Resistance, Viral; Foscarnet; Ganciclovir; Humans; Valganciclovir; Viremia

Despite the use of a cytomegalovirus (CMV) prevention strategy of antiviral prophylaxis for high-risk CMV-seronegative liver transplant recipients with seropositive donors, high rates of delayed-onset postprophylaxis CMV disease occur. An alternate approach, preemptive therapy (initiation of antiviral therapy for early asymptomatic CMV viremia detected by surveillance testing), has not previously been directly compared with antiviral prophylaxis in these patients.. To compare preemptive therapy with antiviral prophylaxis in CMV-seronegative liver transplant recipients with seropositive donors for the prevention of CMV disease.. Randomized clinical trial of preemptive therapy vs antiviral prophylaxis in 205 CMV-seronegative liver transplant recipients with seropositive donors aged older than 18 years. The trial was conducted at 6 academic transplant centers in the United States between October 2012 and June 2017, with last follow-up in June 2018.. Patients were randomized 1:1 to receive either preemptive therapy (valganciclovir, 900 mg, twice daily until 2 consecutive negative tests a week apart) for viremia detected by weekly plasma CMV polymerase chain reaction for 100 days (n = 100) or valganciclovir, 900 mg, daily for 100 days as antiviral prophylaxis (n = 105).. The primary outcome was incidence of CMV disease by 12 months, defined as CMV syndrome (CMV viremia and clinical or laboratory findings) or end-organ disease. Secondary outcomes included acute allograft rejection, opportunistic infections, graft and patient survival, and neutropenia.. Among 205 patients who were randomized (mean age, 55 years; 62 women [30%]), all 205 (100%) completed the trial. The incidence of CMV disease was significantly lower with preemptive therapy than antiviral prophylaxis (9% [9/100] vs 19% [20/105]; difference, 10% [95% CI, 0.5% to 19.6%]; P = .04]). The incidence of allograft rejection (28% vs 25%; difference, 3% [95% CI, -9% to 15%]), opportunistic infections (25% vs 27%; difference, 2% [95% CI, -14% to 10%]), graft loss (2% vs 2%; difference, <1% [95% CI, -4% to 4%]), and neutropenia (13% vs 10%; difference, 3% [95% CI, -5% to 12%]) did not differ significantly for the preemptive therapy vs antiviral prophylaxis group, respectively. All-cause mortality at last follow-up was 15% in the preemptive therapy vs 19% in the antiviral prophylaxis group (difference, 4% [95% CI, -14% to 6%]; P = .46).. Among CMV-seronegative liver transplant recipients with seropositive donors, the use of preemptive therapy, compared with antiviral prophylaxis, resulted in a lower incidence of CMV disease over 12 months. Further research is needed to replicate these findings and assess long-term outcomes.. ClinicalTrials.gov Identifier: NCT01552369.

Topics: Adult; Aged; Antibiotic Prophylaxis; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Incidence; Liver Transplantation; Male; Middle Aged; Polymerase Chain Reaction; Tissue Donors; Valganciclovir; Viral Load; Viremia

Maribavir is a benzimidazole riboside with activity against cytomegalovirus (CMV). The safety and efficacy of maribavir for preemptive treatment of CMV infection in transplant recipients is not known.. In a phase 2, open-label, maribavir dose-blinded trial, recipients of hematopoietic-cell or solid-organ transplants (≥18 years of age, with CMV reactivation [1000 to 100,000 DNA copies per milliliter]) were randomly assigned to receive maribavir at a dose of 400, 800, or 1200 mg twice daily or the standard dose of valganciclovir for no more than 12 weeks. The primary efficacy end point was the percentage of patients with a response to treatment, defined as confirmed undetectable CMV DNA in plasma, within 3 weeks and 6 weeks after the start of treatment. The primary safety end point was the incidence of adverse events that occurred or worsened during treatment.. Of the 161 patients who underwent randomization, 159 received treatment, and 156 had postbaseline data available - 117 in the maribavir group and 39 in the valganciclovir group. The percentage of patients with postbaseline data available who had a response to treatment within 3 weeks was 62% among those who received maribavir and 56% among those who received valganciclovir. Within 6 weeks, 79% and 67% of patients, respectively, had a response (risk ratio, 1.20; 95% confidence interval, 0.95 to 1.51). The percentages of patients with a response to treatment were similar among the maribavir dose groups. Two patients who had a response to treatment had a recurrence of CMV infection within 6 weeks after starting maribavir at a dose of 800 mg twice daily; T409M resistance mutations in CMV UL97 protein kinase developed in both patients. The incidence of serious adverse events that occurred or worsened during treatment was higher in the maribavir group than in the valganciclovir group (52 of 119 patients [44%] vs. 13 of 40 [32%]). A greater percentage of patients in the maribavir group discontinued the trial medication because of an adverse event (27 of 119 [23%] vs. 5 of 40 [12%]). A higher incidence of gastrointestinal adverse events was reported with maribavir, and a higher incidence of neutropenia was reported with valganciclovir.. Maribavir at a dose of at least 400 mg twice daily had efficacy similar to that of valganciclovir for clearing CMV viremia among recipients of hematopoietic-cell or solid-organ transplants. A higher incidence of gastrointestinal adverse events - notably dysgeusia - and a lower incidence of neutropenia were found in the maribavir group. (Funded by ViroPharma/Shire Development; EudraCT number, 2010-024247-32.).

Topics: Adult; Aged; Allografts; Antiviral Agents; Benzimidazoles; Cytomegalovirus; Cytomegalovirus Infections; Dysgeusia; Female; Gastrointestinal Diseases; Hematopoietic Stem Cell Transplantation; Humans; Intention to Treat Analysis; Male; Middle Aged; Neutropenia; Organ Transplantation; Ribonucleosides; Valganciclovir; Viremia; Virus Activation

The clinical utility of the QuantiFERON-CMV (QFN-CMV) assay in heart transplant recipients was assessed. Forty-four cytomegalovirus (CMV)-seropositive patients were enrolled: 17 received antiviral prophylaxis, and 27 were managed preemptively. CMV-DNAemia monitoring was performed by the use of a quantitative real-time PCR assay. The QFN-CMV assay was retrospectively performed on blood samples collected at five posttransplant time points. A higher proportion of patients with an indeterminate QFN-CMV result after the suspension of prophylaxis than of patients who showed a global T-cell responsiveness developed CMV infection (

Topics: Adult; Aged; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Heart Transplantation; Humans; Immunity, Cellular; Italy; Male; Middle Aged; Monitoring, Immunologic; Real-Time Polymerase Chain Reaction; Retrospective Studies; Transplant Recipients; Valganciclovir; Viral Load; Viremia; Young Adult

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections are a significant cause of morbidity and mortality in transplant recipients and are often transmitted from the donor organ.. In a pilot prospective, randomized, double-blinded, placebo-controlled trial, we studied whether 14 days of pretransplant donor treatment with valganciclovir (valG) versus placebo reduced donor-to-recipient transmission, making posttransplant recipient prophylaxis more effective in reducing EBV and CMV disease.. Seventeen D+ R- donor-recipient pairs were enrolled: 7 and 10 donors were randomized to valG and placebo, respectively. At study initiation, no donor had detectable CMV replication, five had EBV replication (two in valG, three in placebo group): EBV replication was undetectable during valG treatment, but resumed on stopping valG. Valganciclovir was tolerated without side effects or leukopenia. All recipients received routine posttransplant viral prophylaxis with valG. For recipients, viremia-free survival time, incidence, range, peak, and duration of CMV and EBV viremia were not significantly different between groups. There was no disease in the valG group but two serious viral diseases occurred in the placebo group (one CMV; one EBV-related posttransplant lymphoproliferative disorder). In the case of posttransplant lymphoproliferative disorder, the EBV DNA from the donor's oral wash and the recipient's lymphoid tissue biopsy had identical latent membrane protein 1 (LMP-1) sequence variations from the reference EBV strain, making it highly probable that the recipient's virus was of donor origin.. Based on this pilot trial, we recommend an adequately powered study to determine if pretransplant donor treatment with valG can reduce posttransplant CMV and EBV disease with merely routine posttransplant recipient viral prophylaxis.

Topics: Adolescent; Adult; Aged; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus Infections; Double-Blind Method; Epstein-Barr Virus Infections; Female; Ganciclovir; Humans; Infant; Kidney Transplantation; Living Donors; Male; Middle Aged; Pilot Projects; Prospective Studies; Valganciclovir; Viremia; Virus Replication; Young Adult

Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). This pilot prospective randomized clinical trial compares valganciclovir (VGV) to ganciclovir (GCV) as pre-emptive therapy for CMV viremia in the post-allogeneic HSCT population.. Patients undergoing allogeneic HSCT who were at risk for CMV viremia were monitored post HSCT by weekly quantitative whole blood polymerase chain reaction. Pre-emptive therapy was delayed until the viral load (VL) was >10,000 copies/mL once, or >5000 copies/mL twice. Patients were randomized to either GCV 5 mg/kg twice a day (b.i.d.) for 7 days followed by daily GCV 5 mg/kg for up to 21 days, or VGV 900 mg b.i.d. for 7 days followed by 900 mg daily for up to 21 days. The primary endpoint was clearance of viremia (VL <5000 copies/mL) within 28 days of initiation of therapy.. In total, 37 patients were enrolled; 19 patients received treatment with VGV and 18 patients received treatment with GCV. The VGV was not inferior in efficacy to GCV as pre-emptive therapy, with rates of viral clearance at 28 days of 89.5% and 83%, respectively (P-value for non-inferiority = 0.030). Toxicities were similar between the 2 arms. No patients developed CMV disease.. In this trial, the rates of clearance of viremia appear to be similar with VGV and GCV.

Topics: Administration, Oral; Adolescent; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Pilot Projects; Polymerase Chain Reaction; Prospective Studies; Transplantation, Homologous; Valganciclovir; Viral Load; Viremia; Young Adult

The epidemiology of cytomegalovirus infection (CMV) in islet transplantation (IT) is not well defined. This study defines incidence, transmission and clinical sequelae of CMV reactivation or disease in 121 patients receiving 266 islet infusions at a single institution. The donor (D)/recipient (R) serostatus was D+/R- 31.2%, D+/R+ 26.3%, D-/R+ 13.2% and D-/R- 29.3%. CMV prophylaxis with oral ganciclovir/valganciclovir was given in 68%. CMV infection occurred in 14/121 patients (11.6%); six had asymptomatic seroconversion and eight others had positive viremia (six asymptomatic and two with CMV febrile symptoms). Median peak viral loads were 1755 copies/mL (range 625-9 100 000). Risk factors for viremia included lymphocyte depletion (thymoglobulin or alemtuzumab, p < 0.001). Viremia was more common in D+/R+ versus D+/R- (p = 0.12), occurring mostly late after transplant (median 306 days). Presumed transmission from IT occurred in 8/83 of D+/R- procedures (9.6%). Of the two cases of CMV disease, one resulted from islet transmission from a CMV positive donor (D+/R-); the other was due to de novo exogenous infection (D-/R-). Therefore, CMV transmission presents rarely after IT and with low incidence compared to solid organ transplantation, but occurs late posttransplant. The use of lymphocyte depleting therapies is a primary risk factor.

Topics: Antiviral Agents; Canada; Cytomegalovirus; Cytomegalovirus Infections; Diabetes Mellitus, Type 1; Female; Ganciclovir; Graft Survival; Humans; Incidence; Islets of Langerhans Transplantation; Lymphocyte Depletion; Male; Postoperative Complications; Prognosis; Risk Factors; Survival Rate; T-Lymphocytes; Transplantation Immunology; Treatment Outcome; Valganciclovir; Viral Load; Viremia

In a randomized study, we observed a higher incidence of biopsy-proven acute rejection with pre-emptive valganciclovir therapy as compared with valacyclovir prophylaxis for prevention of cytomegalovirus (CMV) disease after renal transplantation (RTx). Persistence of the virus within the allograft could stimulate the alloimmune response. The aim of our study was to evaluate intragraft CMV infection in patients randomized to the trial.. RTx recipients at risk of CMV were randomized to pre-emptive therapy with valganciclovir (n=36) for significant CMV viraemia (> or =2,000 copies/ml by quantitative PCR in whole blood samples) or 3-month prophylaxis with valacyclovir (n=34). Renal biopsies performed during 12 months post-RTx were analysed for the presence of CMV by real-time PCR and immunohistochemical staining.. A total of 35 patients (59 biopsies) in the pre-emptive group and 31 patients (57 biopsies) with valacyclovir prophylaxis had > or =1 biopsy specimen with sufficient material for intragraft CMV determination. Cumulative incidence of intragraft CMV infection was 14% and 7% (P=0.315) with pre-emptive therapy and prophylaxis, respectively. Patients at risk for primary CMV infection (CMV serological donor-positive and recipient-negative) were at higher risk for intragraft CMV infection (40% versus 5%; P=0.008). CMV viraemia at the time of biopsy was associated with the presence of CMV within the allograft (P<0.001).. During the first year after RTx, the incidence of intragraft CMV infection was relatively low with comparable rates in patients managed by pre-emptive valganciclovir therapy and valacyclovir prophylaxis.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Ganciclovir; Graft Rejection; Humans; Kidney Transplantation; Postoperative Complications; Premedication; Risk Factors; Transplantation, Homologous; Treatment Outcome; Valacyclovir; Valganciclovir; Valine; Viremia

Late-onset cytomegalovirus (CMV) disease is a significant problem with a standard 3-month prophylaxis regimen. This multicentre, double-blind, randomized controlled trial compared the efficacy and safety of 200 days' versus 100 days' valganciclovir prophylaxis (900 mg once daily) in 326 high-risk (D+/R-) kidney allograft recipients. Significantly fewer patients in the 200-day group versus the 100-day group developed confirmed CMV disease up to month 12 posttransplant (16.1% vs. 36.8%; p < 0.0001). Confirmed CMV viremia was also significantly lower in the 200-day group (37.4% vs. 50.9%; p = 0.015 at month 12). There was no significant difference in the rate of biopsy-proven acute rejection between the groups (11% vs. 17%, respectively, p = 0.114). Adverse events occurred at similar rates between the groups and the majority were rated mild-to-moderate in intensity and not related to study medication. In conclusion, this study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days' prophylaxis, without significant additional safety concerns associated with longer treatment. The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5.

Topics: Antiviral Agents; Biopsy; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Female; Ganciclovir; Humans; Incidence; Kidney; Kidney Transplantation; Male; Middle Aged; Risk Factors; Safety; Valganciclovir; Viremia

Cytomegalovirus (CMV) is the most prevalent opportunistic infection after lung transplantation. Current strategies do not prevent CMV in most at-risk patients.. To determine whether extending prophylaxis with oral valganciclovir from the standard 3 months to 12 months after lung transplantation is efficacious.. Randomized, clinical trial. Patients were randomly assigned by a central automated system to treatment or placebo. Patients and investigators were blinded to treatment status. (ClinicalTrials.gov registration number: NCT00227370). Multicenter trial involving 11 U.S. lung transplant centers.. 136 lung transplant recipients who completed 3 months of valganciclovir prophylaxis.. 9 additional months of oral valganciclovir (n = 70) or placebo (n = 66).. The primary end point was freedom from CMV disease (syndrome or tissue-invasive) on an intention-to-treat basis 300 days after randomization. Secondary end points were CMV disease severity, CMV infection, acute rejection, opportunistic infections, ganciclovir resistance, and safety.. CMV disease occurred in 32% of the short-course group versus 4% of the extended-course group (P < 0.001). Significant reductions were observed with CMV infection (64% vs. 10%; P < 0.001) and disease severity (110 000 vs. 3200 copies/mL, P = 0.009) with extended treatment. Rates of acute rejection, opportunistic infections, adverse events, CMV UL97 ganciclovir-resistance mutations, and laboratory abnormalities were similar between groups. During the 6 months after study completion, a low incidence of CMV disease was observed in both groups.. Longer-term effects of extended prophylaxis were not assessed.. In adult lung transplant recipients who have received 3 months of valganciclovir, extending prophylaxis by an additional 9 months significantly reduces CMV infection, disease, and disease severity without increased ganciclovir resistance or toxicity. A beneficial effect with regard to prevention of CMV disease seems to extend at least through 18 months after transplantation.

Topics: Administration, Oral; Adult; Antiviral Agents; Cytomegalovirus Infections; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Ganciclovir; Humans; Lung Transplantation; Male; Middle Aged; Opportunistic Infections; Pneumonia, Viral; Prospective Studies; Valganciclovir; Viremia

Despite its widespread use in the management of HIV-related cytomegalovirus (CMV) infection, there have been surprisingly few reports of the use of valganciclovir (VGC) in the post-allotransplant setting. So far, no multi-center, non-crossover trial data have been available with the use of this drug as the primary pre-emptive. The present study evaluated the efficacy and safety of VGC for preemptive therapy of CMV infection after allogeneic hematopoietic stem cell transplantation (HSCT).. From January to April 2007, VGC was adopted in eleven centers in mainland China for pre-emptive therapy of CMV infection in consecutive patients undergoing allogeneic HSCT. Allogeneic HSCT recipients were followed weekly via CMV pp65 antigenemia assay or real-time quantitative polymerase chain reaction (PCR) for detection of CMV-DNA. Patients with a positive assay were treated with VGC, 900 mg P.O. twice a day for 14 days followed by 900 mg P.O. once a day for 14 days after a negative result or the CMV-DNA load was lower.. A total of 54 patients (15 siblings, 28 mismatched related donors, 11 unrelated donors) had a positive assay treated with oral VGC. The seroconversion rate was 89% (48/54) as confirmed by a negative assay; six patients failed oral VGC. No significant toxicity was encountered. No case of CMV disease was diagnosed in the responding patients with a median follow-up of 5.3 months after the drug administration.. Pre-emptive therapy of CMV viraemia with oral VGC is safe and effective in allogeneic HSCT.

Topics: Adolescent; Adult; Antiviral Agents; China; Cytomegalovirus Infections; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Valganciclovir; Viremia; Young Adult

Though an important cause of morbidity and mortality in solid organ transplantation (SOT), the long-term outcomes of cytomegalovirus (CMV) disease treatment have not been well studied. In a randomized trial, 321 SOT recipients with CMV disease were followed 1 year after treatment with either twice daily intravenous ganciclovir or oral valganciclovir (for 21 days) followed by once daily valganciclovir until day 49 in all patients. Clinical and viral eradication of CMV disease was similar between groups. Clinical recurrence beyond day 49 was found in 15.1% and virological recurrence in 30.0%, no difference between groups (p > 0.77). In a multivariable logistic regression analysis, the only independent predictor for recurrence was failure to eradicate DNAemia by day 21 (clinical: OR 3.9 [1.3-11.3], p = 0.012; virological: OR 5.6 [2.5-12.6], p < 0.0001). Eight patients developed ganciclovir resistance, with no difference between groups (p = 0.62). Twenty patients (valganciclovir: 11, ganciclovir: 9, p = 0.82) died, 12 due to infections, two involving CMV disease. There were no differences in long-term outcomes between treatment arms, further supporting the use of oral valganciclovir for treatment of CMV disease. Persistent DNAemia at day 21, CMV IgG serostatus and development of resistance may be relevant factors for further individualization of treatment.

Topics: Adult; Antibodies, Viral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance; Ethnicity; Female; Ganciclovir; Humans; Immunoglobulin G; Injections, Intravenous; Male; Middle Aged; Multivariate Analysis; Organ Transplantation; Regression Analysis; Treatment Outcome; Valganciclovir; Viral Load; Viremia

The efficacy of valganciclovir as preemptive therapy for the prevention of cytomegalovirus (CMV) disease and its impact on indirect sequelae of CMV were assessed in recipient-negative/donor-positive (R-/D+) liver transplant recipients. Of 187 consecutive liver transplant recipients at our institution since July 2001, 36 (19.2%) belonged to the R-/D+ group. Surveillance tests for CMV were performed on all patients at weeks 2, 4, 6, 8, 10,12, and 16. In all, 27 patients with asymptomatic viremia received preemptive therapy with valganciclovir. At a total follow-up of 62.8 patient years (median: 19 months, range: 3 months to 5.6 years), no episodes of CMV disease were documented in these patients. The incidence of rejection, retransplantation, and bacterial or fungal infections and the probability of survival did not differ for R-/D+ patients and all non-R-/D+ patients treated preemptively with valganciclovir (P > 0.20 for all variables). Thus, preemptive therapy with valganciclovir in R-/D+ patients was not associated with CMV disease during the period of surveillance monitoring or at anytime thereafter (late-onset CMV disease). The indirect outcomes with the use of valganciclovir in R-/D+ patients were comparable to the outcomes of other subgroups of liver transplant recipients receiving preemptive therapy.

Topics: Adult; Aged; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Ganciclovir; Humans; Liver; Liver Transplantation; Male; Middle Aged; Phosphoproteins; Recurrence; Time Factors; Tissue Donors; Transplantation, Homologous; Treatment Outcome; Valganciclovir; Viral Load; Viral Matrix Proteins; Viremia

The aims of this prospective, open-label, single-center pilot study were to assess the efficacy and safety of human cytomegalovirus (HCMV) prophylaxis using valganciclovir in HCMV- seropositive kidney-transplant patients to prevent HCMV infection and disease. Fifty-one HCMV seropositive kidney-transplant patients recipients who received transplants between 1 December 2005 and 30 November 2006 were included in the study. Valganciclovir was given from transplantation up to 114 (37-329) days, and was adapted to renal function, i.e., 900 mg/d if calculated creatinine clearance was >60 ml/min, or 450 mg/day if it was <60 ml/min. HCMV DNAemia was assessed every 2 weeks during prophylaxis, and on the same basis for 3 months post-prophylaxis. Immunosuppression was based on calcineurin inhibitors (ciclosporine A=22; tacrolimus=11), with mycophenolate mofetil (n=51), and low-dose steroids. Eighteen patients received no calcineurin-inhibitors, but Belatacept instead. During valganciclovir prophylaxis, asymptomatic HCMV DNAemia was observed in one patient, and no case of HCMV disease occurred. Within 252 days (45-425) post-valganciclovir prophylaxis, HCMV DNAemia was detected in 23.5% (n=12) of patients, of whom two had two or more consecutive HCMV DNAemias. Valganciclovir prophylaxis in HCMV-seropositive kidney-transplant patients is effective for preventing cytomegalovirus disease.

Topics: Adult; Aged; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Pilot Projects; Valganciclovir; Viremia; Virus Activation

A series of substudies of a large international cytomegalovirus (CMV) prophylaxis trial investigated the incidence and clinical relevance of reactivation of human herpesviruses 6, 7, and 8, varicella zoster virus, Epstein-Barr virus, polyomavirus, and adenovirus, and the effect of CMV prophylaxis on clinical and subclinical non-CMV viral infections, in adult solid organ transplant (SOT) patients. Results of the substudy analyses showed that viremia caused by a number of viruses is surprisingly common posttransplantation; most of these infections likely represent reactivation of endogenous latent virus. In addition, although infection or active viral replication was common in this cohort of SOT patients, symptomatic disease due to these viruses was uncommon and the clinical sequelae of viremia were unclear or not apparent. CMV prophylaxis may have modified the natural history of some of these non-CMV viral infections.

Topics: Antiviral Agents; BK Virus; Cytomegalovirus Infections; Double-Blind Method; Epstein-Barr Virus Infections; Ganciclovir; Herpesvirus 4, Human; Herpesvirus 6, Human; Herpesvirus 7, Human; History, 16th Century; Humans; Organ Transplantation; Polyomavirus Infections; Postoperative Complications; Valganciclovir; Viremia; Virus Activation

A randomized, double-blind study was conducted to evaluate the pharmacokinetics of ganciclovir following oral administration of ganciclovir or valganciclovir for prophylaxis of cytomegalovirus (CMV) disease in solid organ transplant recipients (n = 240/372).. The correlations between individual exposure to ganciclovir during prophylaxis, with CMV viremia incidence during and after treatment, CMV disease up to 12 months posttransplant, and hematological toxicity were assessed.. Mean daily areas under the curve (AUCs) of ganciclovir from valganciclovir and oral ganciclovir were 46.3 +/- 15.2 and 28.0 +/- 10.9 microg.h/ml (mean +/- SD), respectively. Viremia was suppressed during prophylaxis when exposure to ganciclovir was 40-50 microg.h/ml, AUCs typical of those achieved in valganciclovir-treated patients. The development of viremia 1 month after ending prophylaxis was also reduced with higher ganciclovir AUC (median predicted incidence, 20% and 10% at AUCs of 33 and 50 microg h/ml, respectively). The development of CMV disease within 1 year of transplant was 17.6% and independent of prophylactic exposure to ganciclovir. There was only a weak tendency to increased neutropenia and leukopenia with higher ganciclovir exposure.. The greater systemic exposure to ganciclovir delivered by valganciclovir was associated with delayed development of viremia. There was only a weak association between AUC and hematological toxicity.

Topics: Administration, Oral; Antiviral Agents; Area Under Curve; Body Height; Body Weight; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Female; Ganciclovir; Humans; Male; Middle Aged; Organ Transplantation; Postoperative Complications; Valganciclovir; Viral Load; Viremia

Cytomegalovirus (CMV) D+/R- solid-organ transplant (SOT) recipients carry increased risk of developing CMV disease; however, other risk factors in these patients have not been delineated.. We examined 20 demographic and clinical variables for their association with the development of CMV disease, as defined by an independent endpoint committee (IEC) and also by the investigator (investigator treated [IT]), or CMV viremia within 12 months of transplant in D+/R- transplant recipients who received prophylaxis with valganciclovir or oral ganciclovir for 100 days.. Recipients with low creatinine clearance (Ccr,<40 mL/min) at screening had a significantly increased hazard of developing IEC-defined CMV disease (hazards ratio [HR]=4.28, confidence interval [CI] 1.69, 10.83). Females were twice as likely (HR=2.19, CI .21, 3.99) to develop IEC-defined CMV disease than males. These variables were associated with an increased risk of IEC-defined CMV disease in time-dependent models. Recipients with blood group A were also more likely to develop IEC-defined CMV disease than those with group O (HR=2.36 CI 1.24, 4.51) in the logistic regression model only. Prophylactic drug, organ type, recipient age, rejection episodes, and maintenance immunosuppression regimen were not associated with IEC-defined CMV disease. Female sex was the only variable associated with the development of CMV viremia (odds ratio [OR]=1.65; CI 1.03, 2.65) and IT CMV disease (OR=1.78; CI 1.08, 2.93).. Low Ccr at screening and blood type A are risk factors for IEC-defined CMV disease, and female sex was a risk factor for IEC- and IT-defined CMV disease and viremia in high-risk SOT recipients. These variables should perhaps be considered when optimizing treatment.

Topics: ABO Blood-Group System; Adolescent; Adult; Antiviral Agents; Creatinine; Cytomegalovirus Infections; Double-Blind Method; Female; Ganciclovir; Humans; Logistic Models; Male; Middle Aged; Organ Transplantation; Proportional Hazards Models; Risk Factors; Sex Factors; Time Factors; Valganciclovir; Viremia

There is a paucity of data on the impact of cytomegalovirus (CMV) serostatus and CMV infection on outcomes in facial vascularized composite allotransplantation.. This international, multicenter, retrospective cohort study presents data on CMV and basic transplant-related demographics, including pretransplant viral D/R serostatus, and duration of antiviral prophylaxis. CMV-related complications (viremia, disease), allograft-related complications (rejection episodes, loss), and mortality were analyzed.. We included 19 patients, 4 of whom received CMV high-risk transplants (D+/R-). CMV viremia was noted in 6 patients (all 4 D+/R- patients and 2 D-/R+), mostly within the first-year posttransplant, shortly after discontinuation of antiviral prophylaxis (median 2 mo). CMV disease occurred in 2 D+/R- patients. The high-risk group experienced relatively more rejection episodes per month follow-up. None of D+/R- patients suffered allograft loss due to rejection (longest follow-up: 121 mo).. D+/R- patients were at increased risk of CMV-related complications. Although a higher number of rejections was noted in this group, none of the D+/R- patients lost their allograft or died because of CMV or rejection. Thus, CMV D+/R- face transplantation can likely be safely performed with prophylaxis, active surveillance, and prompt treatment.

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Humans; Retrospective Studies; Valganciclovir; Vascularized Composite Allotransplantation; Viremia

Cytomegalovirus (CMV) is a common opportunistic infection in patients after liver transplant (LT). Guidelines recommend 900 mg daily of valganciclovir; however, valganciclovir commonly causes dose-dependent hematologic toxicities. Use of a low-dose valganciclovir (450 mg) has been used to prevent these adverse effects, but the data regarding this dosing strategy are not as robust in a steroid sparing LT center.. Retrospective chart review of adult LT recipients between January 1, 2008 and June 30, 2019. All patients received low-dose valganciclovir 450 mg PO daily for CMV prophylaxis. Primary outcome was the incidence of CMV viremia in LT recipients at 12 months post-LT. Secondary outcomes include time to CMV viremia, risk factors for the development of CMV viremia, and incidence of breakthrough CMV viremia while on valganciclovir prophylaxis.. A total of 266 patients were included. Overall, the majority were male (63.2%) and Caucasian (45.5%). The most common indication for transplant was decompensated cirrhosis (82%). The incidence of CMV at 1 year posttransplant was 7.9%. Independent risk factors included high risk status (OR 5.97, 95% CI 2.14-16.61, p = .001) as well as having an episode of rejection (OR 5.99, 95% CI 2.16-16.66, p = .001).. Low-dose valganciclovir can be effective in the prevention of CMV viremia in LT patients and may be a beneficial strategy for CMV prophylaxis in a steroid-sparing transplant center. Further studies may be needed to determine appropriate length of prophylaxis therapy for different risk groups.

Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Incidence; Liver Transplantation; Male; Retrospective Studies; Risk Factors; Steroids; Transplant Recipients; Valganciclovir; Viremia

Letermovir is a novel agent for the prevention of cytomegalovirus (CMV) infection and disease that, unlike traditional CMV DNA polymerase inhibitors, does not carry the risk of myelosuppression. The purpose of this study was to evaluate the safety, efficacy, and clinical application of letermovir for CMV prophylaxis in heart transplant (HT) recipients. Between November 1, 2019, and October 1, 2021, at a single, tertiary care hospital, 17 HT recipients were initiated on letermovir due to leukopenia while on valganciclovir. Fifteen (88%) had high-risk mismatch (CMV D+/R-). Median time on letermovir was 5 months (interquartile range, 2-8 months.) At the end of the study period, nine of 17 patients (52.9%) were still on letermovir and four of the 17 (23.5%) had successfully completed the prophylaxis window on letermovir and been switched to the pre-emptive strategy. One patient developed clinically significant CMV viremia in the setting of being unable to obtain medication due to insurance barriers but was later successfully restarted on letermovir. One patient was unable to tolerate letermovir due to symptoms of headache and myalgias. Two patients developed low-level non-clinically significant CMV viremia and were switched back to valacyclovir. All patients had tacrolimus dosages reduced at time of letermovir initiation to minimize the risk of supratherapeutic tacrolimus concentration. One patient required hospitalization due to symptomatic tacrolimus toxicity. For HT recipients who cannot tolerate valganciclovir, letermovir presents an alternative for CMV prophylaxis. Close monitoring for breakthrough CMV and calcineurin inhibitor levels is necessary. Larger studies are required to further delineate its use and help provide further evidence of its safety and efficacy.

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Heart Transplantation; Humans; Tacrolimus; Transplant Recipients; Valganciclovir; Viremia

As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for vaccines to protect individuals at high risk for complications and to potentially control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge about adverse events of SARS-CoV-2 vaccines during post-marketing surveillance. Varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation has already been reported in COVID-19 patients. In addition, adverse events after SARS-CoV-2 mRNA vaccination have also been in the context of varicella zoster virus (VZV) reactivation and directly associated with the mRNA vaccine. We present the first case of CMV reactivation and pericarditis in temporal association with SARS-CoV-2 vaccination, particularly adenovirus-based DNA vector vaccine ChAdOx1 nCoV-19 against SARS-CoV-2. After initiation of antiviral therapy with oral valganciclovir, CMV viremia disappeared and clinical symptoms rapidly improved. Since huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must be in place to assess vaccine safety that is important for the detection of any events. In the context of the hundreds of millions of individuals to be vaccinated against SARS-CoV-2, a potential causal association with CMV reactivation may result in a considerable number of cases with potentially severe complications.

Topics: Aged; Antiviral Agents; ChAdOx1 nCoV-19; COVID-19; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Pericarditis; SARS-CoV-2; Treatment Outcome; Valganciclovir; Viremia; Virus Activation

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.. 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.. 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.. 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

Persistent viral replication resulting in ongoing cytomegalovirus (CMV) viremia despite adequate therapy is difficult to manage and associated with negative outcomes. We report a case series of kidney transplant recipients receiving adjunctive letermovir in combination with valganciclovir for refractory CMV.. Adult patients receiving a kidney or kidney-pancreas transplant were included if they developed CMV viremia and initiated letermovir 480 mg daily as part of a dual therapy regimen with valganciclovir 900 mg twice daily between 1/9/2020 and 31/12/2020. Included patients received ≥90 days of valganciclovir and had a detectable viral load less than 1000 Iu/ml (log. Eight patients were included. Letermovir was added 223 ± 105 days after initiation of CMV treatment with ganciclovir derivatives. Median viral load at initiation was 139.7 (range: 73-355) IU/ml and did not clear or change significantly after 2, 4 and 12 weeks of adjunctive letermovir (132.5 [range: 34.5-513] IU/ml vs. 68.7 [range: 34.5-574] IU/ml vs. 78.3 [range: 34.5-347] IU/ml, p > 0.05). Tacrolimus was reduced by ∼30% in anticipation of a letermovir-tacrolimus drug interaction. Despite this reduction, mean tacrolimus serum levels two weeks after adjunctive letermovir increased by 43% (5.6 ± 1.6 ng/ml vs 8.0 ± 4.6 ng/ml).. In kidney and kidney-pancreas recipients with refractory CMV, the use of adjunctive letermovir did not result in viral clearance. Additionally, despite a mean tacrolimus dose reduction of 30% at letermovir initiation, serum concentrations increased by over 40%. Further investigation into the optimal approach to refractory CMV is needed.

Topics: Acetates; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Quinazolines; Transplant Recipients; Valganciclovir; Viremia

Viral infections are controlled primarily by viral-specific T cells, raising concern for adequate T-cell response to clear CMV infection in transplant recipients receiving lymphocyte-depleting agents (LDA). We examined the rates of CMV viremia and clearance, seroconversion, and CMV-specific CD8+ T cell (CMV-Tc) activity with class of induction agent received.. Retrospective review of 45 pediatric renal transplant recipients who received induction with LDA (n = 31) or non-LDA (NLDA; n = 14) received valganciclovir prophylaxis for 6 months post-transplant and CMV-PCR monitoring. CMV-Tc was measured by intracellular IFNγ flow cytometry, when possible, at baseline, 1 month after CMV viremia (>5 copies/PCR) and serially until CMV-Tc was positive (≥0.2%).. Viremia rates at 1, 2, and 4 years post-transplant were higher in LDA vs. NLDA (46.3% vs. 7.2%, 64.2% vs. 7.2%, and 64.2% vs. 7.2%, respectively; p = .002). Viremia rates at these time points in seronegative LDA (50.3%, 71.6%, 71.6%) were significantly or near significantly higher than seronegative NLDA (9.1%, 9.1%, 9.1%; p = .004), seropositive-LDA (22.3%, 22.3%, 22.3%; p = .07), or seropositive NLDA (0%, 0%, 0%; p = .07). Eleven of 17 (64.7%) viremic subjects required valganciclovir dose reduction during the prophylaxis period for leukopenia. All viremic LDA patients developed CMV-Tc. One viremic NLDA patient did not develop CMV-Tc. No patients developed CMV disease.. CMV seronegative pediatric renal transplant patients receiving LDA are more likely to have valganciclovir prophylaxis dose reduction and develop subclinical CMV viremia; however, all developed CMV-Tc. Larger prospective studies are needed to further understand the effects of induction agents on CMV-Tc and CMV-Tc's role post-transplant.

Topics: Adolescent; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus Infections; Female; Graft Rejection; Humans; Infant; Kidney Transplantation; Lymphocyte Depletion; Male; Postoperative Complications; Retrospective Studies; T-Lymphocytes, Cytotoxic; Transplant Recipients; Transplantation, Homologous; Valganciclovir; Viremia; Young Adult

The role of antiviral prophylaxis to prevent Epstein-Barr virus (EBV) viremia or posttransplant lymphoproliferative disorder in pediatric solid organ transplant recipients is controversial. We examined whether valganciclovir (VAL) prophylaxis for cytomegalovirus infection was associated with EBV viremia following transplantation in EBV-naive children.. A single-center, retrospective study was conducted of EBV-naive pediatric heart and renal transplant recipients with an EBV-positive donor from January 1996 to April 2017. VAL was tested for association with EBV viremia-free survival in the first 6 months posttransplantation when immunosuppressant exposure is the highest. Survival models evaluated VAL duration, with adjustment for other baseline confounders.. Among the cohort (n = 44), 3 (6.8%) were heart transplants, 25 (56.8%) received VAL, and 22 (50%) developed EBV viremia in the first-year posttransplantation. Mean time-to-viremia was 143 vs. 90 days for the VAL and no-VAL groups, respectively (p = 0.008), in the first 6 months. Only two patients developed viremia while on VAL. Each additional day of VAL was associated with 1.4% increase in viremia-free survival (p < 0.001). Multivariable modeling of VAL with other baseline risk factors did not identify other independent risk factors.. VAL is independently associated with delayed onset of EBV viremia, with prolongation of delay with each additional day of antiviral prophylaxis.

Topics: Adolescent; Antiviral Agents; Child; Disease-Free Survival; Epstein-Barr Virus Infections; Female; Graft Survival; Humans; Immunosuppression Therapy; Male; Multivariate Analysis; Organ Transplantation; Proportional Hazards Models; Retrospective Studies; Transplant Recipients; Valganciclovir; Viremia

Topics: BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Humans; Kidney Diseases; Polyomavirus Infections; Valganciclovir; Viremia

Topics: BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Valganciclovir; Viremia

Topics: BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Humans; Polyomavirus Infections; Risk Factors; Valganciclovir; Viremia

Human cytomegalovirus (HCMV) can be managed by monitoring HCMV DNA in the blood and giving valganciclovir when viral load exceeds a defined value. We hypothesised that such pre-emptive therapy should occur earlier than the standard 3000 genomes/ml (2520 IU/ml) when a seropositive donor transmitted virus to a seronegative recipient (D+R-) following solid organ transplantation (SOT).. Our local protocol was changed so that D+R- SOT patients commenced valganciclovir once the viral load exceeded 200 genomes/ml; 168 IU/ml (new protocol). The decision point remained at 3000 genomes/ml (old protocol) for the other two patient subgroups (D+R+, D-R+). Virological outcomes were assessed three years later, when 74 D+R- patients treated under the old protocol could be compared with 67 treated afterwards. The primary outcomes were changes in peak viral load, duration of viraemia and duration of treatment in the D+R- group. The secondary outcome was the proportion of D+R- patients who developed subsequent viraemia episodes.. In the D+R- patients, the median values of peak viral load (30,774 to 11,135 genomes/ml, p<0.0215) were significantly reduced on the new protocol compared to the old, but the duration of viraemia and duration of treatment were not. Early treatment increased subsequent episodes of viraemia from 33/58 (57%) to 36/49 (73%) of patients (p< 0.0743) with a significant increase (p = 0.0072) in those episodes that required treatment (16/58; 27% versus 26/49; 53%). Median peak viral load increased significantly (2,103 to 3,934 genomes/ml, p<0.0249) in the D+R+ but not in the D-R+ patient subgroups. There was no change in duration of viraemia or duration of treatment for any patient subgroup.. Pre-emptive therapy initiated at the first sign of viraemia post-transplant significantly reduced the peak viral load but increased later episodes of viraemia, consistent with the hypothesis of reduced antigenic stimulation of the immune system.

Topics: Adult; Antiviral Agents; Clinical Protocols; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Organ Transplantation; Recurrence; Secondary Prevention; Tissue Donors; Valganciclovir; Viral Load; Viremia

Lung transplantation has a high risk of cytomegalovirus (CMV) viremia and disease.. Valganciclovir was planned for 6 months in CMV recipient seropositive (R+) lung transplants (LTs) and given long-term in D+R- LTs. CMV viremia was monitored regularly during and after prophylaxis in all patients.. Prophylaxis for 6 months in D+R+ and D-R+, and past 12 months in D+R- LTs, with long-term monitoring in all patients using a sensitive assay, and reinstitution of valganciclovir for low-level viremia was effective at markedly reducing the incidence of CMV disease. CMV D-R- LTs do not need routine CMV monitoring.

Topics: Adult; Antiviral Agents; Australia; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Incidence; Lung Transplantation; Male; Middle Aged; Valganciclovir; Viral Load; Viremia

Cytomegalovirus (CMV) outcomes with valganciclovir prophylaxis in renal transplant recipients experiencing delayed graft function (DGF) are unclear.. This single center, retrospective, cohort study of CMV high-risk (D+/R- with alemtuzumab induction) deceased donor renal transplant recipients receiving valganciclovir prophylaxis assessed CMV outcomes in patients experiencing DGF (n = 72) versus those with immediate graft function (IGF; n = 66).. Cytomegalovirus viremia by 12 months occurred at similar rates in the IGF and DGF groups (30.3% vs 26.4%, respectively, P = 0.71) with 89.7% (35/39) of all cases classified as CMV disease. The median time to CMV viremia post transplant was day 141 and 138 in the IGF and DGF groups, respectively (P = 0.30). The incidence of biopsy-proven acute rejection (BPAR) was higher in the DGF group (18.1% vs 4.6%, P = 0.02) with BPAR preceding CMV in only 1 patient. There was no significant difference in graft loss (1.5% vs 4.2%, P = 0.62) or patient survival (98.5% vs 95.8%, P = 0.62) at 1 year between the IGF and DGF groups, respectively.. Valganciclovir prophylaxis in patients experiencing DGF yielded similar CMV outcomes up to 1-year post transplant when compared to use in patients with IGF.

Topics: Adult; Antiviral Agents; Cytomegalovirus Infections; Delayed Graft Function; Electronic Health Records; Female; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Risk Factors; Transplant Recipients; Treatment Outcome; Valganciclovir; Viremia

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.

Topics: Adult; BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Female; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Polyomavirus Infections; Premedication; Proportional Hazards Models; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Tumor Virus Infections; Valacyclovir; Valganciclovir; Viremia

Despite universal prophylaxis, late cytomegalovirus (CMV) infection occurs in a high proportion of kidney transplant recipients. We evaluated whether a specific viral T-cell response allows for the better identification of recipients who are at high risk of CMV infection after prophylaxis withdrawal.. We conducted a prospective study in 19 pretransplant anti-CMV seronegative kidney graft recipients R- (18 from seropositive donors [D+] and one from a seronegative donor [D-]) and 67 seropositive recipients R(+) (59 from seropositive donors and eight from seronegative donors) who received antiviral prophylaxis with valganciclovir. The QuantiFERON-CMV (QF-CMV) assay was performed within the first and third months after transplantation. Blood samples were monitored for CMV DNAemia using a commercial quantitative nucleic acid amplification test (QNAT) that was calibrated to the World Health Organization International Standard.. Twenty-one of the 86 patients (24%) developed CMV viremia after prophylaxis withdrawal within 12 months posttransplantation. In the CMV R(+) group, the QF-CMV assay yielded reactive results (QF-CMV[+]) in 51 of 67 patients (76%) compared with 7 of 19 patients (37%) in the CMV R(-) group (p = 0.001). In the CMV R(+) group, infection occurred in seven of 16 recipients (44%) who were QF-CMV(-) and eight of 51 recipients (16%) who were QF-CMV(+). In the CMV R(-) group, infection evolved in five of 12 recipients (42%) who were QF-CMV(-) and one of 7 recipients (14%) who were QF-CMV(+). No difference was found in the incidence of CMV infection stratified according to the QF-CMV results with regard to the recipients' pretransplant CMV IgG serology (p = 0.985). Cytomegalovirus infection occurred in 15 of 36 patients (42%) with hypogammaglobulinemia (HGG) 90 days posttransplantation compared with two of 34 patients (6%) without HGG (p = 0.0004). Cytomegalovirus infection occurred in seven of 13 patients (54%) with lymphocytopenia compared with 14 of 70 patients (20%) without lymphocytopenia (p = 0.015). The multivariate analysis revealed that the nonreactive QuantiFERON-CMV assay was an independent risk factor for postprophylaxis CMV infection.. In kidney transplant recipients who received posttransplantation prophylaxis, negative QF-CMV results better defined the risk of CMV infection than initial CMV IgG status after prophylaxis withdrawal. Hypogammaglobulinemia and lymphocytopenia were risk factors for CMV infection.

Topics: Adult; Aged; Antibodies, Viral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Follow-Up Studies; Humans; Incidence; Kidney Transplantation; Male; Middle Aged; Prospective Studies; T-Lymphocytes; Tissue Donors; Transplant Recipients; Valganciclovir; Viremia

We describe a case of an adult with dermatomyositis (DM) who presents with a rash, high fevers, tachycardia and hypotension, initially concerning for an infectious aetiology or a DM flare. She was found to have cytomegalovirus viraemia which improved after starting valganciclovir. After extensive workup and lack of improvement with broad-spectrum antimicrobial therapy, intravenous immunoglobulin and steroids, the patient was diagnosed with macrophage activation syndrome after bone marrow biopsy and levels of soluble CD25 (soluble interleukin (IL)-2 receptor) and IL2 were obtained. Unfortunately, despite therapy with dexamethasone, anakinra and etoposide, the patient decompensated and the patient's family opted for comfort care. The patient subsequently expired in the intensive care unit.

Topics: Cytomegalovirus Infections; Dermatomyositis; Fatal Outcome; Female; Ganciclovir; Humans; Immunoglobulins, Intravenous; Macrophage Activation Syndrome; Middle Aged; Valganciclovir; Viremia

A 39-year-old male, who received a facial allograft (cytomegalovirus [CMV] donor-seropositive, recipient-seronegative), developed multidrug-resistant CMV infection despite valganciclovir prophylaxis (900 mg/day) 6 months post transplantation. Lower extremity weakness with upper and lower extremity paresthesias developed progressively 11 months post transplantation, coinciding with immune control of CMV. An axonal form of Guillain-Barré syndrome was diagnosed, based on electrophysiological evidence of a generalized, non-length-dependent, sensorimotor axonal polyneuropathy. Treatment with intravenous immunoglobulin led to complete recovery without recurrence after 6 months.

Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Multiple, Viral; Facial Transplantation; Ganciclovir; Guillain-Barre Syndrome; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Male; Time Factors; Valganciclovir; Viral Load; Viremia

Kidney transplant patients with D+/R+ serology can be treated with either prophylaxis or preemptive valganciclovir. The older transplant population suffers severe immunosenescence, especially patients with latent cytomegalovirus (CMV) infection (R+). They are more likely to develop indirect CMV effects. Likewise, many patients have significant cardiovascular comorbidity, which makes them more sensitive to these indirect effects. The aim of this study was to evaluate the incidence of CMV viremia and indirect effects on survival, comparing prophylaxis (V) against preemptive (P) valganciclovir in an older kidney transplant population.. We analyzed the data of 233 recipients from 2002 (age, >55 years; D+/R+) with ≥6 months of follow-up. The patients were divided into 2 groups: 167 (71.7%) in the V group and 66 (28.3%) in the P group.. The incidence of CMV infection in the P group was 32% versus 6% in V group. Patients with CMV viremia showed worse survival values than patients without viremia (log rank P = .031). Five-year survivals were 74% vs 88%, respectively. Cox regression showed that the adjusted effect of CMV infection on overall survival was a significant risk (hazard ratio [HR], 2.07; 95% CI, 1.003-4.29). Patients with CMV viremia showed worse cardiovascular survival than patients without viremia, with 5-year survivals of 79% vs 94%. Cox regression showed that the adjusted effect of CMV infection was a significant risk (HR, 2.62).. CMV infection has a detrimental effect on the survival of older patients. Valganciclovir prophylaxis induces a protective effect against CMV infection and could improve survival of older patients with cardiovascular comorbidities.

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Epidemiologic Methods; Female; Ganciclovir; Humans; Kidney Transplantation; Male; Middle Aged; Recurrence; Time Factors; Valganciclovir; Viremia

A number of studies have demonstrated that cytomegalovirus (CMV) viraemia is a strong predictor for CMV end-organ disease (EOD) and death in HIV-infected patients. We assess the efficacy and safety of pre-emptive anti-CMV therapy (PACT) for preventing these events. We performed a retrospective study of all HIV-infected patients seen in our institution who had detectable CMV viraemia in 2007. Seventy-one patients with advanced HIV disease (median CD4 cell count = 61 cells/mm(3)) were studied. Sixteen patients received PACT (mainly valganciclovir). Patients who received PACT had lower CD4 cell counts and higher blood CMV DNA levels. The cumulative incidence of CMV EOD and death at one year was 44% and 21% in patients with and without PACT, respectively (p = 0.013). Both PACT and high blood CMV DNA levels were significantly associated with CMV EOD and death in unadjusted analysis. In adjusted analyses, only blood CMV DNA levels remained significantly associated with the risk of CMV EOD and death, whereas PACT was associated with a non-significant trend towards reduced CMV EOD or death (hazard ratio: 0.25, p = 0.13). Five patients with PACT experienced severe drug-related adverse events. In conclusion, the use of PACT in HIV-infected patients with CMV viraemia could improve outcome but is associated with significant toxicity.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Ganciclovir; HIV Infections; Humans; Immunocompromised Host; Incidence; Male; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Treatment Outcome; Valganciclovir; Viral Load; Viremia

This study compared the pre-emptive and the prophylactic strategies used to prevent cytomegalovirus (CMV) infection and disease in CMV-seropositive orthotopic liver-transplant recipients and searched for associated predictive factors. Seventy-three orthotopic liver-transplant recipients who had received a transplant before November 2005 were given ganciclovir IV pre-emptively (group I) and 56 recipients who had received a transplant after November 2005 were given prophylactic valganciclovir for 3 months (group II). Demographic and biochemical parameters did not statistically vary between the groups at baseline. Monitoring of CMV DNAemia was similar in both groups. Forty-two (57.5%) patients presented with CMV infection in group I and 18 (32.1%) in group II (P < 0.004). CMV DNAemia was first detected at a median of 33 days post-transplant in group I and at 98.5 days in group II (P < 0.003), but viral loads were not significantly different. The overall incidence of CMV disease was 9.6% in group I versus 7.1% in group II (ns). Thirty-five (47.9%) patients presented with biopsy-proven acute rejection in group I and 13 (23.2%) in group II (P = 0.004). Forty (55%) patients in group I and 25 (44.6%) in group II presented with de novo post-transplant diabetes (P = 0.057). At 1-year post-transplant, global survival curves were not significantly different. Independent factors associated with CMV reactivation were an absence of CMV prophylaxis, CMV serological status of the donor, cold ischemia time, and HLA A + B + DR compatibility. CMV prophylaxis is efficacious and can prevent safely the direct and indirect effects of CMV infection in CMV-seropositive orthotopic liver-transplant recipients.

Topics: Adult; Aged; Antiviral Agents; Chemoprevention; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Ganciclovir; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Liver Transplantation; Male; Middle Aged; Survival Analysis; Time Factors; Transplant Recipients; Valganciclovir; Viral Load; Viremia; Young Adult

Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Ganciclovir; Humans; Male; Middle Aged; Multiple Myeloma; Stem Cell Transplantation; Valganciclovir; Viremia

We report on a small bowel transplant patient, donor/recipient seropositive (D+/R+) for cytomegalovirus (CMV), with a clinical course complicated by CMV disease. Anti-CMV prophylaxis was given for 100 days. Immunosuppression consisted of alemtuzumab, tacrolimus, mycophenolate mofetil and prednisolone. Five months posttransplant, CMV tissue invasive disease of the upper gastrointestinal tract was evident without the presence of viremia, tested by quantitative polymerase chain reaction (PCR). Complete viral load suppression was achieved with intravenous ganciclovir, followed by valganciclovir for secondary prophylaxis. Mycophenolate mofetil and prednisolone were discontinued. Shortly thereafter the patient presented with recurrent CMV and candida esophagitis. While on ganciclovir and caspofungin, the patient developed CMV tissue invasive disease of the ileal graft, with persistent absence of viremia. Foscarnet and CMV immunoglobulin were added. Viral load declined to undetectable levels; however, clinical improvement did not occur due to occurrence of graft rejection. Despite infliximab and high dose prednisolone, graft rejection was progressive, requiring surgical explantation of the graft. This case highlights the importance of additional diagnostic tools such as endoscopy including PCR analysis of tissue samples. Extension of primary antiviral prophylaxis interval up to 6 months and prolonged retreatment for recurrent CMV disease may be useful to avoid severe CMV-related complications.

Topics: Administration, Intravenous; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunocompromised Host; Intestinal Diseases; Intestine, Small; Middle Aged; Organ Transplantation; Real-Time Polymerase Chain Reaction; Transplant Recipients; Valganciclovir; Viral Load; Viremia

Cytomegalovirus (CMV) is a major cause of morbidity and mortality following solid organ transplantation (SOT). Two strategies, prophylactic, and preemptive have emerged for the prevention of CMV infection and disease after SOT. This retrospective chart review of two liver transplant cohorts: prophylactic and preemptive, compares the clinical impact of transitioning from prophylactic to preemptive strategy. The primary outcome is the incidence of CMV viremia at 3-and 6-months post-transplant. Secondary outcomes include: incidence of CMV tissue-invasive disease, acute cellular rejection, leukopenia and neutropenia, opportunistic infection rates, hospital readmission rates, and mortality at 3-and 6-months post-transplant. A total of 109 patients were included in the analysis. The incidence of CMV viremia was 4.9% and 50.0% (P < 0.001) in the prophylactic versus preemptive cohort, respectively, at 3 months post-transplant. The incidence of CMV viremia was 24.6% and 8.3% (P = 0.026) in the prophylactic versus preemptive cohort, respectively, at 6 months post-transplant. There were no statistical significant differences in the secondary outcomes between both cohorts. In conclusion, there is a statistical significant difference in time to onset of CMV viremia; however, the use of either prophylactic or preemptive strategy was not associated with significant negative clinical outcomes of CMV.

Topics: Adult; Aged; Antiviral Agents; Cohort Studies; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Liver Transplantation; Male; Middle Aged; Neutropenia; Opportunistic Infections; Retrospective Studies; Treatment Outcome; Valganciclovir; Viremia

Topics: Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Liver Transplantation; Male; Opportunistic Infections; Valganciclovir; Viremia

Valganciclovir preemptive therapy guided by the viral load is the current strategy recommended for preventing CMV disease in CMV-seropositive Solid Organ Transplant Recipients (SOTR) at lower risk for developing CMV infection. However, universal viral load cut-off has not been established for initiating therapy.. Our goal was to define and validate a standardized cut-off determined in plasma by real-time PCR assay for initiating preemptive therapy in this population.. A prospective cohort study of consecutive cases of CMV-seropositive SOTR was carried out. The cut-off value was determined in a derivation cohort and was validated in the validation cohort. Viral loads were determined using the Quant CMV LightCycler 2.0 real-time PCR System (Roche Applied Science) and results were standardized using the WHO International Standard for human CMV.. A viral load of 3983 IU/ml (2600 copies/ml) was established as the optimal cut-off for initiating preemptive therapy in a cohort of 141 patients with 982 tests and validated in a cohort of 252 recipients with a total of 2022 test. This cut-off had a 99.6% NPV indicating that the great majority of patients at lower risk will not develop CMV disease without specific antiviral therapy. The high sensitivity and specificity (89.9% and 88.9%, respectively) and the relatively small numbers of patients with CMV disease confirm that real-time PCR was optimal.. We have established a cut-off viral load for starting preemptive therapy for CMV-seropositive SOT recipients. Our results emphasized the importance of a mandatory follow-up protocol for CMV-seropositive patients receiving preemptive treatment.

Topics: Adult; Aged; Antiviral Agents; Clinical Laboratory Techniques; Cohort Studies; Cytomegalovirus Infections; DNA, Viral; Female; Ganciclovir; Humans; Male; Middle Aged; Molecular Diagnostic Techniques; Organ Transplantation; Plasma; Prospective Studies; Real-Time Polymerase Chain Reaction; Valganciclovir; Viral Load; Viremia; Young Adult

Rabbit anti-thymocyte globulin (rATG) induces a long-lasting lymphocytopenia. CD4(+) T cells remain depleted for up to 2 years, whereas the CD8(+) T cell compartment is refilled rapidly by highly differentiated CD27(-) CD45RA(+) CD57(+) effector-type cells. Because the presence of these highly differentiated CD8(+) T cells has been associated with cytomegalovirus (CMV) infection, we questioned to what extent restoration of CMV T cell immunity contributes to the re-emergence of T cells following rATG treatment. We compared T cell repopulation in six CMV-seropositive patients with CMV reactivation (reactivating CMV(+) ) to that in three CMV(+) patients without reactivation (non-reactivating CMV(+) ), and to that in three CMV-seronegative recipients receiving a kidney from a CMV-seronegative donor (CMV(-/-) ). All patients received rATG because of acute allograft rejection. Total CD4 and CD8 counts, frequency and phenotype of virus-specific CD8(+) T cells were determined. In reactivating CMV(+) patients, total CD8(+) T cells reappeared rapidly, whereas in non-reactivating CMV(+) patients they lagged behind. In CMV(-/-) patients, CD8(+) T cell counts had not yet reached pretransplant levels after 2 years. CMV reactivation was indeed followed by a progressive accumulation of CMV-specific CD8(+) T cells. During lymphocytopenia following rATG treatment, serum interleukin (IL)-7 levels were elevated. Although this was most prominent in the CMV-seronegative patients, it did not result in an advantage in T cell repopulation in these patients. Repopulated CD8(+) T cells showed increased skewing in their Vβ repertoire in both CMV(-/-) and reactivating CMV-seropositive patients. We conclude that rapid T cell repopulation following rATG treatment is driven mainly by CMV.

Topics: Adult; Animals; Antilymphocyte Serum; Antiviral Agents; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Ganciclovir; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Graft Rejection; Humans; Immunosuppressive Agents; Interleukin-7; Kidney Transplantation; Lymphocyte Count; Lymphopenia; Male; Middle Aged; Postoperative Complications; Rabbits; Valganciclovir; Viremia; Virus Activation; Young Adult

Cytomegalovirus (CMV) disease after discontinuation of prophylaxis is a significant problem for CMV-seronegative recipients of CMV-seropositive organs (donor seropositive and recipient seronegative [D+/R-]). Virologic monitoring after prophylaxis has been proposed as a way to prevent late-onset disease.. We reviewed the efficacy of this strategy. CMV D+/R- organ transplant recipients received 3 to 6 months of antiviral prophylaxis, and then viral loads were performed weekly for 8 weeks. Preemptive antiviral therapy was initiated at a predefined threshold.. Seventy-one CMV D+/R- patients were assessed. Symptomatic CMV disease occurred in 29 of 71 (40.8%) patients during the first-year posttransplant. A significant portion of disease occurred only after the 8-week surveillance period (n=16). Viremia occurred in 19 of 71 (26.8%) patients during the 8-week surveillance. Preemptive therapy was successfully used in only 3 of 19 (15.8%) viremic patients with no further disease development. The remaining patients cleared low-level viremia spontaneously (n=3) or had CMV disease (n=13) either at the first detection of viremia or before preemptive therapy initiation because of rapid viral load doubling (median doubling time 1.1 days).. CMV D+/R- patients had significant incidence of late-onset disease after prophylaxis. However, the use of a preemptive after prophylaxis strategy was of limited benefit in this group because of rapid viral doubling times and disease occurring after the surveillance period.

Topics: Adolescent; Adult; Aged; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Ganciclovir; Humans; Incidence; Male; Middle Aged; Organ Transplantation; Risk Factors; Time Factors; Treatment Outcome; Valganciclovir; Viral Load; Viremia; Young Adult

To describe a case of cytomegalovirus (CMV) viremia and colitis in a patient on mycophenolate mofetil (MMF) monotherapy for birdshot chorioretinopathy.. Case report.. Retrospective chart review.. Treatment with MMF 1.5 g twice daily for 5 years led to leucopenia and a CD4 count of 299, which resulted in active CMV infection.. Treatment with MMF alone may put otherwise immune-competent individuals at risk for opportunistic CMV infection. Greater awareness of this association may allow for better monitoring, earlier detection, and treatment of future cases.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Birdshot Chorioretinopathy; CD4 Lymphocyte Count; Chorioretinitis; Colitis; Cytomegalovirus Infections; Drug Therapy, Combination; Ganciclovir; Humans; Immunosuppressive Agents; Leukopenia; Male; Mycophenolic Acid; Prednisone; Treatment Outcome; Valganciclovir; Viremia

Primary gastrointestinal cytomegalovirus (CMV) disease after solid organ transplantation (SOT) is difficult to treat and may relapse. Herein, we reviewed the clinical records of CMV D+/R- SOT recipients with biopsy-proven gastrointestinal CMV disease to determine predictors of relapse. The population consisted of 26 kidney (13 [50%]), liver (10 [38%]) and heart (3 [12%]) transplant recipients who developed gastrointestinal CMV disease at a median of 54 (interquartile range [IQR]: 40-70) days after stopping antiviral prophylaxis. Except for one patient, all received induction intravenous ganciclovir (mean+/-SD, 33.8+/-19.3 days) followed by valganciclovir (27.5+/-13.3 days) in 18 patients. Ten patients further received valganciclovir maintenance therapy (41.6+/-28.6 days). The median times to CMV PCR negativity in blood was 22.5 days (IQR: 16.5-30.7) and to normal endoscopic findings was 27.0 days (IQR: 21.0-33.5). CMV relapse, which occurred in seven (27%) patients, was significantly associated with extensive disease (p=0.03). CMV seroconversion, viral load, treatment duration, maintenance therapy and endoscopic findings at the end of therapy were not significantly associated with CMV relapse. In conclusion, an extensive involvement of the gastrointestinal tract was significantly associated with CMV relapse. However, endoscopic evidence of resolution of gastrointestinal disease did not necessarily translate into a lower risk of CMV relapse.

Topics: Adult; Antiviral Agents; Cohort Studies; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Gastrointestinal Diseases; Heart Transplantation; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Polymerase Chain Reaction; Prognosis; Recurrence; Retrospective Studies; Risk Factors; Transplants; Valganciclovir; Viral Load; Viremia

Topics: Antiviral Agents; Cytomegalovirus Infections; Drug Administration Schedule; Ganciclovir; Humans; Kidney Transplantation; Postoperative Complications; Postoperative Period; Time Factors; Valganciclovir; Viremia

Valganciclovir (VGC) is an oral prodrug of ganciclovir (GCV) recently introduced for prophylaxis and treatment of cytomegalovirus infection. Optimal concentration exposure for effective and safe VGC therapy would require either reproducible VGC absorption and GCV disposition or dosage adjustment based on therapeutic drug monitoring (TDM). We examined GCV population pharmacokinetics in solid organ transplant recipients receiving oral VGC, including the influence of clinical factors, the magnitude of variability, and its impact on efficacy and tolerability. Nonlinear mixed effect model (NONMEM) analysis was performed on plasma samples from 65 transplant recipients under VGC prophylaxis or treatment. A two-compartment model with first-order absorption appropriately described the data. Systemic clearance was markedly influenced by the glomerular filtration rate (GFR), patient gender, and graft type (clearance/GFR = 1.7 in kidney, 0.9 in heart, and 1.2 in lung and liver recipients) with interpatient and interoccasion variabilities of 26 and 12%, respectively. Body weight and sex influenced central volume of distribution (V(1) = 0.34 liter/kg in males and 0.27 liter/kg in females [20% interpatient variability]). No significant drug interaction was detected. The good prophylactic efficacy and tolerability of VGC precluded the demonstration of any relationship with GCV concentrations. In conclusion, this analysis highlights the importance of thorough adjustment of VGC dosage to renal function and body weight. Considering the good predictability and reproducibility of the GCV profile after treatment with oral VGC, routine TDM does not appear to be clinically indicated in solid-organ transplant recipients. However, GCV plasma measurement may still be helpful in specific clinical situations.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Female; Ganciclovir; Glomerular Filtration Rate; Humans; Male; Middle Aged; Organ Transplantation; Valganciclovir; Viremia; Young Adult

Efforts to prevent relapsed cytomegalovirus (CMV) disease among solid organ transplant (SOT) recipients present clinical challenges. Historically, SOT recipients treated with short courses of ganciclovir, without documented clearance of viremia, had relapse rates of 23-33%. Current treatment often includes much longer courses of valganciclovir, and persistence of viremia at the end of treatment is rare. We sought to determine the rate and risk factors for relapse under those treatment conditions. Records of 1760 SOT recipients from January 2003 to June 2007 were reviewed; 105 cases of CMV viremia were identified. Relapse occurred in 20/105 (19%); 50% had end-organ disease at the time of relapse. Most patients received approximately 3 months of valganciclovir. Clearance of viremia was documented in 19/20 patients with relapse. Multivariable analysis identified receipt of a thoracic organ and diabetes mellitus as risk factors for relapse. Despite long treatment courses with valganciclovir and documented clearance of viremia, CMV relapse remains common among SOT recipients. Better understanding of the epidemiology of CMV among SOT recipients and validation of risk factors for disease relapse should be the focus of future prospective trials. Such trials should include different treatment durations and extended monitoring for relapse.

Topics: Adult; Aged; Antiviral Agents; Chemoprevention; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Male; Middle Aged; Organ Transplantation; Recurrence; Risk Factors; Valganciclovir; Viremia; Young Adult

Topics: Administration, Oral; Antiviral Agents; Cohort Studies; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Treatment Outcome; Valganciclovir; Viral Load; Viremia; Virus Activation

To investigate the efficacy and safety of valganciclovir in treatment of cytomegalovirus viremia in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).. Nineteen patients following allo-HSCT were diagnosed as with cytomegalovirus viremia with the CMV-DNA load of higher than 6.0 x 10(2) copies/ml confirmed by polymerase chain reaction (PCR) took orally valganciclovir at the dose of 900 mg bid for 14 days followed by 900 mg Qd for another 14 days. Since 4 weeks after the valganciclovir treatment PCR was conducted in the 6th, 8th, 12th, 16th, and 24th weeks later to detect the CMV-DNA level.. CMV viremia was confirmed 40 days after HSCT on average with a median CMV-DNA load of 3.346 x 10(3) copies/ml. The total effective rate of valganciclovir was 94.7% (18/19). The CMV-DNA turned to negative in 7 d in 11 cases with a negative transfer rate of 54.7%, and in 14 d in 16 cases with a negative transfer rate of 84.2%. The median CMV DNA load reduction was 0.75 copies/ml and 0.084 log10 copies/ml/day. Severe adverse effects were not observed and CMV-related disease did not occur.. Valganciclovir is an attractive and safe alternative for preemptive CMV viremia treatment in allo-HSCT recipients.

Topics: Adolescent; Adult; Antiviral Agents; Cytomegalovirus Infections; Female; Follow-Up Studies; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Prospective Studies; Transplantation, Homologous; Treatment Outcome; Valganciclovir; Viremia

The degree of variability in the use of CMV prevention strategies and choice of antiviral regimens among LT centers has not been previously investigated. An electronic survey on current CMV prevention strategies was sent to all US and Canadian LT centers. A total of 58 (53%) centers completed the survey. Most use CMV PCR for screening or diagnosis. Prophylaxis was the most common prevention strategy for all donor/recipient subtypes except D-/R- who often receive no prophylaxis. Prophylaxis was usually given for 3 months after LT with valganciclovir the most frequently used agent. In the small percentage of centers utilizing the preemptive approach, monitoring for CMV was typically performed with PCR for 3 months and valganciclovir was most frequently used for treatment of detectable CMV viremia. In conclusion, the majority of LT centers utilize CMV prophylaxis over other strategies. Valganciclovir is the most commonly used agent for both antiviral prophylaxis and treatment of CMV viremia in the preemptive approach.

Topics: Antiviral Agents; Canada; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Health Care Surveys; Humans; Liver Transplantation; Polymerase Chain Reaction; Prospective Studies; United States; Valganciclovir; Viremia

Cytomegalovirus (CMV)-seronegative recipients (R(-)) of a liver transplant from CMV-positive donors (D(+)) are at high risk for developing late CMV disease after discontinuation of antiviral prophylaxis. Levels of viremia and CMV-specific interferon (IFN)- gamma -producing CD4(+) and IFN- gamma -producing CD8(+) T cell responses were prospectively measured from discontinuation of antiviral prophylaxis until 1 year after transplantation in 17 consecutive D(+)/R(-) patients. CMV loads of >1000 copies/mL were strongly associated with CMV disease in the 6 symptomatic patients. Despite immunosuppression, broadly diverse T cells specific for CMV lysate or peptide libraries spanning pp65 and immediate early (IE) 1 immunodominant CMV antigens developed in all patients. A vigorous CD8(+) T cell response to pp65 and IE1 antigens characterized the D(+)/R(-) cohort. Unexpectedly, none of these responses were predictive of CMV disease or viremia. No significant lymphopenia or functional impairment of CMV-specific T cells was detected in the symptomatic patients, whose morbidity was resolved after antiviral treatment while measurable CMV immunity was maintained during the 1-year observation period.

Topics: Adult; Aged; Antiviral Agents; CD4-Positive T-Lymphocytes; Cohort Studies; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immediate-Early Proteins; Interferon-gamma; Liver Transplantation; Longitudinal Studies; Lymphocyte Count; Male; Middle Aged; Phosphoproteins; Risk Factors; Valganciclovir; Viral Matrix Proteins; Viral Proteins; Viremia

Topics: Administration, Oral; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Valganciclovir; Viremia

A 58-year-old man with warm-antibody-mediated autoimmune hemolytic anemia (AIHA) refractory to prednisolone, azathioprine, splenectomy, rituximab and combination chemotherapy, and with unacceptably high transfusion requirement, was treated with alemtuzumab. After a cumulative dose of 883 mg of alemtuzumab, the AIHA remitted completely, with normalization of hemoglobin and transfusion-independence. The major side effect was reactivation of cytomegalovirus, which was controlled with intravenous and oral ganciclovir. This case showed that alemtuzumab might be of use in therapy-refractory AIHA.

Topics: Alemtuzumab; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antigens, CD; Antigens, Neoplasm; Antiviral Agents; Azathioprine; Blood Transfusion; CD52 Antigen; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance; Ganciclovir; Glycoproteins; Humans; Immunosuppressive Agents; Male; Middle Aged; Prednisolone; Remission Induction; Rituximab; Splenectomy; Valganciclovir; Viremia; Virus Activation

Cytomegalovirus (CMV) infection is common after lung transplantation. We performed a prospective trial of valganciclovir prophylaxis in lung recipients with outcomes compared to matched historical controls. The valganciclovir group (n = 40) (including D+/R- and R+ patients) was prospectively enrolled, and received oral valganciclovir 900 mg once daily for 12 weeks. Historical controls (n = 40) received 12 weeks of daily intravenous ganciclovir if D+/R- or 12 weeks of oral ganciclovir if R+. CMV viral load testing was done at two-week intervals until 6 months posttransplant. Baseline demographics and immunosuppression were comparable in the two groups. The incidence of CMV viremia was 16/40 (40.0%) in the valganciclovir arm versus 18/40 (45%) in the ganciclovir arm (p = NS). The incidence of symptomatic CMV disease was 8/40 (20%) versus 7/40 (17.5%), respectively (p = NS). In both groups viremia, while on prophylaxis, was uncommon (valganciclovir: 0/40 and ganciclovir: 2/40). Peak viral load and time to viremia were similar in the two arms. High rates of viremia and symptomatic disease occurred in the D+/R- patients after discontinuation of prophylaxis. Genotypic CMV sequence analysis demonstrated low rates of ganciclovir resistance in both groups. Valganciclovir prophylaxis had similar efficacy to either intravenous ganciclovir (D+/R- patients), or oral ganciclovir (R+ patients) in lung recipients.

Topics: Administration, Oral; Antibiotic Prophylaxis; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Viral; Female; Ganciclovir; Graft Survival; Humans; Lung Transplantation; Male; Middle Aged; Postoperative Complications; Prospective Studies; Valganciclovir; Viremia; Virus Replication