Cost-effectiveness of maribavir versus conventional antiviral therapies for post-transplant refractory cytomegalovirus infection with or without genotypic resistance: A US perspective.

This study evaluated the cost-effectiveness of maribavir versus investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for post-transplant refractory cytomegalovirus (CMV) infection with or without resistance. A two-stage Markov model was designed using data from the SOLSTICE trial (NCT02931539), real-world multinational observational studies, and published literature. Stage 1 (0-78 weeks) comprised clinically significant CMV (csCMV), non-clinically significant CMV (n-csCMV), and dead states; stage 2 (78 weeks-lifetime) comprised alive and dead states. Total costs (2022 USD) and quality-adjusted life years (QALYs) were estimated for the maribavir and IAT cohorts. An incremental cost-effectiveness ratio was calculated to determine cost-effectiveness against a willingness-to-pay threshold of $100 000/QALY. Compared with IAT, maribavir had lower costs ($139 751 vs $147 949) and greater QALYs (6.04 vs 5.83), making it cost-saving and more cost-effective. Maribavir had higher acquisition costs compared with IAT ($80 531 vs $65 285), but lower costs associated with administration/monitoring ($16 493 vs $27 563), adverse events (AEs) ($11 055 vs $16 114), hospitalization ($27 157 vs $33 905), and graft loss ($4516 vs $5081), thus making treatment with maribavir cost-saving. Maribavir-treated patients spent more time without CMV compared with IAT-treated patients (0.85 years vs 0.68 years), leading to lower retreatment costs for maribavir (cost savings: -$42 970.80). Compared with IAT, maribavir was more cost-effective for transplant recipients with refractory CMV, owing to better clinical efficacy and avoidance of high costs associated with administration, monitoring, AEs, and hospitalizations. These results can inform healthcare decision-makers on the most effective use of their resources for post-transplant refractory CMV treatment.

Leaning towards Cytomegalovirus serological screening in pregnancy to prevent congenital infection: a cost-effectiveness perspective.

OBJECTIVE: To assess the cost-effectiveness of prenatal detection of congenital cytomegalovirus (cCMV) following maternal primary infection in the first trimester within standard pregnancy follow-up or involving population-based screening (serological testing at 7 and 12 weeks of gestation), with or without secondary prevention (valaciclovir) in maternal CMV primary infection. DESIGN: Cost-effectiveness study from the perspective of the French national health insurance system. SETTING: Cost-effectiveness based on previously published probability estimates and associated plausible ranges hypothetical population of 1,000,000 pregnant women. POPULATION: Hypothetical population of 1,000,000 pregnant women. METHODS: Cost-effectiveness of detecting fetal cCMV in terms of the total direct medical costs involved and associated expected outcomes. MAIN OUTCOME MEASURES: Detection rates and clinical outcomes at birth. RESULTS: Moving to a population-based approach for targeting fetal CMV infections would generate high monetary and organizational costs while increasing detection rates from 15% to 94%. This resource allocation would help implementing horizontal equity according to which individuals with similar medical needs should be treated equally. Secondary prevention with valaciclovir had a significant effect on maternal-fetal CMV transmission and clinical outcomes in newborns, with a 58% decrease of severely infected newborns for a 3.5% additional total costs. Accounting for women decision-making (amniocentesis uptake and termination of pregnancy in severe cases) did not impact the cost-effectiveness results. CONCLUSIONS: These findings could fuel thinking on the opportunity of developing clinical guidelines to rule identification of cCMV infection and administration of in-utero treatment. These findings could fuel the development of clinical guidelines on the identification of congenital CMV infection and the administration of treatment in utero. TWEETABLE ABSTRACT: CMV serological screening followed by valaciclovir prevention may prevent 58% to 71% of severe cCMV cases for 38 € per pregnancy.

Cost-effectiveness analysis of cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplant recipients from a US payer perspective.

To evaluate the cost-effectiveness of letermovir versus no prophylaxis for the prevention of cytomegalovirus infection and disease in adult cytomegalovirus-seropositive allogeneic hematopoietic cell transplantation (allo-HCT) recipients. A decision model for 100 patients was developed to estimate the probabilities of cytomegalovirus infection, cytomegalovirus disease, various other complications, and death in patients receiving letermovir versus no prophylaxis. The probabilities of clinical outcomes were based on the pivotal phase 3 trial of letermovir use for cytomegalovirus prophylaxis versus placebo in adult cytomegalovirus-seropositive recipients of an allo-HCT. Costs of prophylaxis with letermovir and of each clinical outcome were derived from published sources or the trial clinical study reports. Incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life year (QALY) gained were used in the model. One-way and probabilistic sensitivity analyses were conducted to explore uncertainty around the base-case analysis. In this model, the use of letermovir prophylaxis would lead to an increase of QALYs (619) and direct medical cost ($1 733 794) compared with no prophylaxis (578 QALYs; $710 300) in cytomegalovirus-seropositive recipients of an allo-HCT. Letermovir use for cytomegalovirus prophylaxis was a cost-effective option versus no prophylaxis with base-case analysis ICER $25 046/QALY gained. One-way sensitivity analysis showed the most influential parameter was mortality rate. The probabilistic sensitivity analysis showed a 92% probability of letermovir producing an ICER below the commonly accepted willingness-to-pay threshold of $100 000/QALY gained. Based on this model, letermovir use for cytomegalovirus prophylaxis was a cost-effective option in adult cytomegalovirus-seropositive recipients of an allo-HCT.

Estimated Cost-effectiveness of Newborn Screening for Congenital Cytomegalovirus Infection in China Using a Markov Model.

Importance: Congenital cytomegalovirus infection (cCMVi) is one of the most common infections associated with childhood hearing loss. Prevention and mitigation of cCMVi-related hearing loss will require an increase in newborn screening, which is not yet available in China. Objective: To estimate the cost-effectiveness of newborn screening strategies for cCMVi from the perspective of the Chinese health care system. Design, Setting, and Participants: A decision tree for a simulated cohort population of 15 000 000 live births was developed to compare the costs and health effects of 3 mutually exclusive interventions: (1) no screening, (2) targeted screening using CMV polymerase chain reaction assay for newborns who fail a universal hearing screening, and (3) universal screening for CMV among all newborns. Markov diagrams were used to evaluate the lifetime horizon (76 years). Main Outcomes and Measures: Cost, hearing-related health outcomes, and incremental cost-effectiveness ratios (ICERs) were estimated based on a direct medical costs perspective. Costs and ICERs were reported in 2018 US dollars. Results: Incidence of cCMVi among newborns was reported to be approximately 0.7% in China. Targeted screening was less costly but also less effective than universal screening, identifying 41% of cases needing antiviral treatment and preventing nearly half of less severe or profound hearing loss. To avoid 1 CMV-related severe or profound hearing loss, 13 and 16 newborns need to be treated by targeted and universal screening, respectively. The ICERs of targeted and universal screening vs no screening were $79 and $2087 per quality-adjusted life-year gained, respectively, at the discounted rate of 3.5%. Both screening options were cost-effective for the Chinese health care system based on the willingness-to-pay threshold of 3 × gross domestic product per capita. The sensitivity analysis showed that the prevalence of cCMVi, as well as diagnosis and treatment costs, were key factors that may be associated with decision-making. Conclusions and Relevance: To achieve cost-effectiveness and best health outcomes, universal screening could be considered for the Chinese population. While the results are specific to China, the model may easily be adapted for other countries.

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

BACKGROUND: Ganciclovir (GCV) and foscarnet (FOS) are the most commonly used antivirals for preemptive treatment of cytomegalovirus (CMV) viremia in recipients of allogeneic hematopoietic cell transplantation (alloHCT). The current literature indicates similar efficacy between these agents. Thus, the primary consideration for choice of initial anti-CMV treatment is the safety profile, time period after alloHCT, and concern of myelosuppression or renal dysfunction. METHODS: Herein, we retrospectively reviewed medical records of 124 alloHCT recipients who received GCV or FOS between April 27, 2014, and December 31, 2015, during the first year post-transplant. Healthcare resource use included drug, hospitalization, home health, dialysis, and growth factor costs. RESULTS: Total duration of therapy was longer in the GCV group (37 days vs 28 days, P = .21) but hospitalization days were similar (9 days) in both groups. The total treatment cost was significantly lower in the GCV group ($38 100 vs $59 400, P < .05). CONCLUSION: Preemptive anti-CMV therapy is associated with major healthcare resource costs, which were greater in patients who required FOS than those who were treated with GCV.

Cytomegalovirus infection and associated hospitalization and costs among individuals undergoing allogeneic hematopoietic stem cell transplant.

Objective: This study utilized a large, national US database to explore the impact of Cytomegalovirus (CMV) infection on hospital services utilization and costs during the first 100 days following allogeneic hematopoietic stem cell transplant (allo-HSCT).Methods: This retrospective, observational cohort study used data from the Premier Healthcare database to identify patients undergoing their first (index) allo-HSCT procedure between 1 January 2006 and 31 March 2015. Three subgroups were analyzed according to CMV-related readmissions during the 100-day follow-up (0, 1, or 2+ readmissions) to compare healthcare utilization and costs.Results: A total of 1610 patients (mean age, 50.5 years; 56.9% male) from 52 US hospitals met the inclusion criteria. During follow-up, 212 (13.2%) patients had 1 (n = 161; 10.0%) or 2+ (n = 51; 3.2%) CMV-related readmissions. The mean ± SD number of all follow-up encounters (inpatient admissions and hospital-based outpatient visits) was similar for the no CMV (3.9 ± 3.9), 1 CMV (3.7 ± 3.9), and 2+ CMV (4.5 ± 3.8) readmission groups (p = .439). Mean total costs of hospital-based healthcare encounters (inpatient admissions and hospital-based outpatient visits) during follow-up were significantly greater in patients who had a CMV readmission ($111,729 [1 CMV readmission]; $184,021 [2+ CMV readmissions]) compared to those without a CMV readmission ($46,064; p < .001]. 100-day follow-up mortality was higher in the CMV vs. non-CMV readmission groups (30.2 vs. 8.2%; p < .001).Conclusions: This large, national database study revealed significantly higher healthcare utilization and costs, as well as mortality, among patients with CMV-related re-hospitalization during the first 100 days post-transplant as compared to patients without CMV-related hospitalization.

Reduced economic burden of AIDS-defining illnesses associated with adherence to antiretroviral therapy.

OBJECTIVES: We assessed the economic burden of AIDS-defining illnesses (ADIs), which was further stratified by adherence to antiretroviral therapy (ART). METHODS AND MATERIALS: A nationwide longitudinal cohort of 18,234 incident cases with HIV followed for 11years was utilized. Adherence to ART was measured by medication possession ratio (MPR). Generalized estimating equations modeling was used to estimate the cost impact of ADIs. RESULTS: Having opportunistic infections increased the annual cost by 9% (varicella-zoster virus infection) to 98% (cytomegalovirus disease), while the annual costs increased by 26% (Kaposi's sarcoma) to 95% (non-Hodgkin's lymphoma) in the year when AIDS-related cancer occurred. ADIs occurred more frequently in the years with low adherence for ART compared to the high-adherence years (e.g., 0.1≤MPR<0.8 vs. MPR≥0.8, event rate of cytomegalovirus disease 4.03% vs. 0.51%). The annual baseline costs in the years with MPR<0.1, 0.1≤MPR<0.8, and MPR≥0.8 were $250, $4,752, and $8,990 (in 2018 USD), respectively. The economic impact of ADIs in the years with low adherence (MPR<0.1) was larger than that in the high-adherence years (MPR≥0.8) (e.g., MPR<0.1 vs. MPR≥0.8, annual cost increased by 244% vs. 9% when candidiasis occurred). CONCLUSIONS: Adherence to ART may increase the baseline medical costs but mitigate the incidence and economic burden of ADIs.

The clinical and economic burden of cytomegalovirus management post allogeneic hematopoietic stem cell transplantation in Japan - a retrospective database study.

Introduction: Reactivation of cytomegalovirus (CMV) infection is a major threat and it causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). There remains, however, a paucity of evidence regarding the economic burden of current CMV management in Japan. The aim of this study is to characterize the healthcare resource utilization (HCRU) and cost incurred for CMV management post allo-HSCT, using a Japanese hospital claims database.Methods: Patients who underwent allo-HSCT between April 2010 and March 2018 were identified and followed up for 180 days.Results: In total, 916 patients were included for analysis and categorized into CMV (-) group and CMV (+) group based on the presence of a CMV episode within 100 days post allo-HSCT. A CMV episode was defined as evidence of receiving at least one dose of the following anti-CMV drugs, ganciclovir, foscarnet, or valganciclovir. The mean (± standard deviation [SD]) total length of stay was 93.6 (± 43.7) days in the CMV (+) group, which was significantly longer than 55.9 (±40.6) days in the CMV (-) group, and this trend was more pronounced in patients with multiple CMV episodes. The mean (±SD) total medical cost within 180 days post allo-HSCT was US$122,328 (±56,977) in the CMV (+) group, while the mean total medical cost was US$75,344 (±43,821) in the CMV (-) group. Moreover, transfusion and antimicrobial use was observed as the major medication cost component, which is suggestive of the indirect effect of CMV episodes.Conclusion: This study demonstrated that CMV episodes post allo-HSCT were associated with increased HCRU and cost.

The Economic Burden of Congenital Cytomegalovirus Disease in the First Year of Life: A Retrospective Analysis of Health Insurance Claims Data in the United States.

PURPOSE: Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in the United States; however, limited data exist regarding the economic burden of cCMV disease (cCMVd) among newborns and infants. The purpose of this study was to compare health care resource utilization and costs between infants with cCMVd at birth and during the first year of life versus matched infants without diagnosed cCMVd. METHODS: Retrospective analyses of health insurance claims data from the MarketScan Commercial Claims and Encounters and Multi-State Medicaid databases (January 1, 2011-December 31, 2016) were conducted. Infants with cCMV diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 771.1 or 078.5; International Classification of Diseases, Tenth Revision, Clinical Modification code P35.1 or B25) were included. Two mutually exclusive periods were examined: initial hospital stay at birth ("birth" analysis) and subsequent 12 months ("postbirth" analysis). Infants with cCMVd in both periods were matched 1:1 to infants without cCMVd based on demographic and clinical characteristics. All-cause costs for cCMVd in infants versus matched control infants were reported in 2016 US dollars. Multivariable regression analyses controlled for additional confounding factors. FINDINGS: In the birth analysis, 397 of 404 newborns with cCMVd (167 vaginal deliveries, 230 cesarean deliveries) were matched to control infants; newborns with cCMVd had an additional mean (95% CI) of 9.1 (5.8-12.3) and 9.0 (4.6-13.5) inpatient days and $24,274 (10,082-38,466) and $31,770 (9911-53,630) more unadjusted inpatient costs versus control infants for vaginal and cesarean deliveries, respectively. In the postbirth analysis, 678 of 679 infants with cCMVd were matched with control infants; infants with cCMVd had an additional $58,806 (95% CI, 41,247-76,365) in unadjusted costs versus control infants, with inpatient visits accounting for 85% of the difference. Newborns with cCMVd accrued costs at birth averaging 1.5 to 2.1 times greater than control infants for cesarean and vaginal deliveries. During the first year of life, infants with cCMVd had costs averaging 7 times greater than control infants. IMPLICATIONS: cCMVd is associated with substantial economic burden from birth and during the first year of life. Our findings support the notion that developing effective prevention of cCMVd and increasing awareness of the disease among women should be a public health priority, given the economic burden of cCMVd.

Economic cost of congenital CMV in the UK.

OBJECTIVE: Congenital cytomegalovirus (cCMV) is the most common infectious cause of congenital disability. It can disrupt neurodevelopment, causing lifelong impairments including sensorineural hearing loss and developmental delay. This study aimed, for the first time, to estimate the annual economic burden of managing cCMV and its sequelae in the UK. DESIGN: The study collated available secondary data to develop a static cost model. SETTING: The model aimed to estimate costs of cCMV in the UK for the year 2016. PATIENTS: Individuals of all ages with cCMV. MAIN OUTCOME MEASURES: Direct (incurred by the public sector) and indirect (incurred personally or by society) costs associated with management of cCMV and its sequelae. RESULTS: The model estimated that the total cost of cCMV to the UK in 2016 was £732 million (lower and upper estimates were between £495 and £942 million). Approximately 40% of the costs were directly incurred by the public sector, with the remaining 60% being indirect costs, including lost productivity. Long-term impairments caused by the virus had a higher financial burden than the acute management of cCMV. CONCLUSIONS: The cost of cCMV is substantial, predominantly stemming from long-term impairments. Costs should be compared against investment in educational strategies and vaccine development programmes that aim to prevent virus transmission, as well as the value of introducing universal screening for cCMV to both increase detection of children who would benefit from treatment, and to build a more robust evidence base for future research.

Clinical and Economic Impact of Cytomegalovirus Infection among Children Undergoing Allogeneic Hematopoietic Cell Transplantation.

The literature on the impact of cytomegalovirus (CMV)-related hospitalization in pediatric allogeneic hematopoietic cell transplantation (alloHCT) recipients is limited. The aim of this study was to determine utilization and outcomes of CMV-related hospitalization in alloHCT recipients using a single-center clinical database. This was a retrospective study of 240 children aged 3 months to 21 years (median age, 9.5 years) who underwent alloHCT between 2005 and 2016. The impacts of CMV-related length of stay (LOS) and total healthcare costs were quantified. Factors associated with prolonged CMV viremia (>25 days' duration) were also examined. In at-risk patients with CMV infection, the incidence of CMV viremia was 38% (59 of 155), the median time to onset was 33 days (range, 0 to 292 days), and the median time to resolution was 25 days (range, 3 to 48 days; n = 53). CMV infection was associated with a 23.3-day increase in LOS (P = .004) and added hospital costs of $45,443 (P = .162) compared with patients without CMV infection. In multivariable analysis, receipt of alemtuzumab (P = .027) was associated with CMV viremia of >25 days' duration. Our data show that CMV viremia is associated with prolonged LOS and higher hospital costs and indicate the need for improved and cost-effective CMV prevention strategies. Further studies of patient outcomes and costs in pediatric alloHCT recipients is needed.

Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation.

Patients treated with allogeneic hematopoietic cell transplantation (HCT) are at risk of cytomegalovirus (CMV) reactivation and disease, which results in increased morbidity and mortality. Although universal antiviral prophylaxis against CMV improves outcomes in solid organ transplant recipients, data have been conflicting regarding such prophylaxis in patients undergoing allogeneic HCT. We conducted a systematic review of randomized trials of prophylactic antivirals against CMV after allogeneic HCT to summarize the evolution of the field over the last 35 years and evaluate the prophylactic potential of antiviral agents against CMV after allogeneic HCT. Electronic databases were queried from database inception through 31 December 2017. For included studies, incidence of CMV infection and all-cause mortality were collected as primary outcomes; CMV disease incidence, use of preemptive therapy, and drug toxicities were collected as secondary outcomes. Nineteen clinical trials conducted between 1981 and 2017 involving a total of 4173 patients were included for review. Prophylactic strategies included use of acyclovir, valacyclovir, ganciclovir, maribavir, brincidofovir, and letermovir compared with placebo or a comparator antiviral. Fourteen trials that compared antiviral prophylaxis with placebo demonstrated overall effectiveness in reducing incidence of CMV infection (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.42-0.58), CMV disease (OR, 0.56; 95% CI, 0.40-0.80), and use of preemptive therapy (OR, 0.51; 95% CI, 0.42-0.62; 6 trials); however, none demonstrated reduction in all-cause mortality (OR, 0.96; 95% CI, 0.78-1.18) except the phase 3 trial of letermovir (week-24 OR, 0.59; 95% CI, 0.38-0.98). Additional research is warranted to determine patient groups most likely to benefit from antiviral prophylaxis and its optimal deployment after allogeneic HCT.

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation.

BACKGROUND: CMV infection (CMV-I) remains an important complication of hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective, single-center cohort study in HSCT recipients. Primary outcomes were adjusted cost and all-cause mortality. Secondary analyses investigated CMV risk factors and the effect of serostatus. RESULTS: Overall, 690 transplant episodes were included (allogeneic [n = 310]; autologous [n = 380]). All received preemptive CMV antiviral therapy at first detectable DNAemia. CMV-I occurred in 34.8% of allogeneic and 2.1% of autologous transplants; median time to onset was 45 days. In allogeneic HSCT recipients, the primary risk factor for CMV-I was CMV donor/recipient (D/R) serostatus. In a Markov multi-state model for allogeneic HSCT recipients, the hazard ratio for CMV-I and relapse was 1.5 (95% CI 0.8-2.8) and for CMV-I and mortality 2.4 (95% CI 0.9-6.5). In a multivariable model for all patients, CMV-I was associated with increased total cost (coefficient = 0.21, estimated incremental daily cost USD $500; P = 0.02). Cost was attenuated in allogeneic HSCT recipients (coefficient = 0.13, USD $699 vs $613, or $24 892 per transplant episode; P = 0.23). CMV disease (CMV-D) complicated 29.6% of CMV-I events in allogeneic HSCT recipients, but was not associated with an incrementally increased adjusted risk of mortality compared with CMV-I alone. CMV-I (56.4%) and CMV-D (19.8%) were significantly overrepresented in D-/R+ serostatus HSCT recipients, and mortality was higher in R+ HSCT recipients. CONCLUSIONS: Despite early preemptive antiviral treatment, CMV-I impacts clinical outcomes and cost after HSCT, but the impact on cost is less pronounced in allogeneic HSCT recipients compared with autologous HSCT recipients.

Cytomegalovirus reactivation and disease amongst patients with allogeneic haematopoietic stem cell transplantation in Eastern India: Epidemiology, outcome and healthcare cost.

PURPOSE: Data from developing countries about incidence, prognosis and healthcare cost of cytomegalovirus (CMV) reactivation amongst patients with allogeneic hematopoietic stem cell transplantation (AHSCT) remain scarce. The purpose of the study was to describe the epidemiology, outcome and cost implications of CMV reactivation and CMV disease amongst patients with AHSCT in cancer hospital in Eastern India. MATERIALS AND METHODS: The study design was a retrospective audit of clinical records. RESULTS: Ninety-nine per cent of patients and 94% of the donors were found to be CMV seropositive. CMV reactivation rate was 43.8% amongst patients with AHSCT (n = 130 patients). CMV reactivation occurred 118 days after AHSCT (median; range: 28-943 days). Patients with any grade of graft-versus-host disease (GVHD) had higher CMV reactivation rate than patients without GVHD. Patients with CMV reactivation had more frequent GVHD than patients without CMV reactivation. Use of steroids was associated with CMV reactivation. We found no differences in overall survival of patients with or without CMV reactivation. The cost of in-house CMV-polymerase chain reaction at our centre was USD $57 (Rs. 3650), cost for intravenous ganciclovir was USD $26 (Rs. 1665) per infusion and oral valganciclovir USD $8 (Rs. 512)/900 mg tablet. The median duration of anti-CMV therapy was 14 days (interquartile range: 14-28 days) and the average cost per patient per month directed towards CMV management ranged between USD $800 and USD $1,300 (Rs. 51,238-Rs. 83,264). Three patients (2.3%) in this series had CMV disease, all of whom died. CONCLUSION: In an increasingly globalised world, where medical tourism is common, data from developing countries regarding cost and outcome of CMV infections in AHSCT patients are of relevance.

Risk Factors, Geographic Distribution, and Healthcare Burden of Symptomatic Congenital Cytomegalovirus Infection in the United States: Analysis of a Nationally Representative Database, 2000-2012.

OBJECTIVE: To assess risk factors, geographic distribution, length of stay, and total charges per case of symptomatic congenital cytomegalovirus infection (cCMV). STUDY DESIGN: We performed retrospective analyses of serial cross-sectional data using the Kids' Inpatient Database, a nationally representative sample of US pediatric hospital discharges, from 2000, 2003, 2006, 2009, and 2012. Symptomatic cCMV was identified via use of the International Classification of Diseases, Ninth Revision, Clinical Modification code 771.1 among records with in-hospital birth that were accompanied by 1 or more characteristic symptoms. Demographic characteristics were compared with multivariable logistic regression. Temporal trend was assessed using linear regression. Charges were adjusted for inflation to 2012 US dollars. RESULTS: We identified 1349 cases of symptomatic cCMV (SE 56). Symptomatic cCMV was associated with non-Hispanic black race (OR 1.70; 95% CI 1.37-2.10), government-sponsored insurance (OR 1.95; 95% CI 1.34-2.83), and birth in the American South and West (OR 1.68, 95% CI 1.35-2.09 and OR 1.61, 95% CI 1.23-2.09, respectively). In-hospital mortality and preterm birth rate ranged from 3.2%-6.8% and 50.4%-59.2%, respectively, without temporal changes. The geometric mean of total charges per case doubled from $45 771 (SE $8509) in 2000 to $89 846 (SE $10 358) in 2006 (P = .002) but did not change from 2006 to 2012. Length of stay in days was 15 (IQR 8-22) in 2000, 27 (IQR, 9-51) in 2009, and 18 (IQR, 8-47) in 2012. CONCLUSIONS: Symptomatic cCMV was associated with non-Hispanic black race, low socioeconomic status, and birth in the American South and West and resulted in substantial healthcare burden.

Healthcare costs attributable to congenital cytomegalovirus infection.

OBJECTIVE: Congenital cytomegalovirus infection (cCMV) can cause symptoms at birth as well as long-term impairment. This study estimates cCMV-related healthcare costs in the Netherlands in early childhood. DESIGN, SETTING AND PATIENTS: In a nationwide retrospective cohort study, 156 children with cCMV were identified by testing 31 484 neonatal dried blood spots for cCMV. Use of healthcare resources in the first 6 years of life by children with cCMV and a matched cCMV-negative control group were analysed. Mean costs per child were calculated by multiplying healthcare resource use by its reference prices. EXPOSURE: Children with cCMV were compared with cCMV-negative children. MAIN OUTCOME MEASURES: The average total healthcare costs per child were based on the average costs for hospital admissions and consultations by healthcare providers. RESULTS: Mean healthcare costs of children with cCMV (€6113, n=133) were higher than children without cCMV (€3570, n=274), although statistically not significant, with a mean difference of €2544 (95% CI €-451 to €5538). The costs of children with long-term impairment were two times higher in children with cCMV (€17 205) compared with children without cCMV (€8332). CONCLUSIONS: Children with cCMV, especially those with long-term impairment and those symptomatic at birth, accrue higher healthcare costs than cCMV-negative children in the first 6 years of life, although this is not statistically significant. This economic impact is of importance in the evaluation of preventive measures against cCMV. TRIAL REGISTRATION NUMBER: NTR3582.

A Markov Analysis of Screening for Late-Onset Cytomegalovirus Disease in Cytomegalovirus High-Risk Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Management strategies are unclear for late-onset cytomegalovirus infection occurring beyond 6 months of antiviral prophylaxis in cytomegalovirus high-risk (cytomegalovirus IgG positive to cytomegalovirus IgG negative) kidney transplant recipients. Hybrid strategies (prophylaxis followed by screening) have been investigated but with inconclusive results. There are clinical and potential cost benefits of preventing cytomegalovirus-related hospitalizations and associated increased risks of patient and graft failure. We used decision analysis to evaluate the utility of postprophylaxis screening for late-onset cytomegalovirus infection. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used the Markov decision analysis model incorporating costs and utilities for various cytomegalovirus clinical states (asymptomatic cytomegalovirus, mild cytomegalovirus infection, and cytomegalovirus infection necessitating hospitalization) to estimate cost-effectiveness of postprophylaxis cytomegalovirus screening strategies. Five strategies were compared: no screening and screening at 1-, 2-, 3-, or 4-week intervals. Progression to severe cytomegalovirus infection was modeled on cytomegalovirus replication kinetics. Incremental cost-effectiveness ratios were calculated as a ratio of cost difference between two strategies to difference in quality-adjusted life-years starting with the low-cost strategy. One-way and probabilistic sensitivity analyses were performed to test model's robustness. RESULTS: There was an incremental gain in quality-adjusted life-years with increasing screening frequency. Incremental cost-effectiveness ratios were $783 per quality-adjusted life-year (every 4 weeks over no screening), $1861 per quality-adjusted life-year (every 3 weeks over every 4 weeks), $10,947 per quality-adjusted life-year (every 2 weeks over every 3 weeks), and $197,086 per quality-adjusted life-year (weekly over every 2 weeks). Findings were sensitive to screening cost, cost of hospitalization, postprophylaxis cytomegalovirus incidence, and graft loss after cytomegalovirus infection. No screening was favored when willingness to pay threshold was <$14,000 per quality-adjusted life-year, whereas screening weekly was favored when willingness to pay threshold was >$185,000 per quality-adjusted life-year. Screening every 2 weeks was the dominant strategy between willingness to pay range of $14,000-$185,000 per quality-adjusted life-year. CONCLUSIONS: In cytomegalovirus high-risk kidney transplant recipients, compared with no screening, screening for postprophylactic cytomegalovirus viremia is associated with gains in quality-adjusted life-years and seems to be cost effective. A strategy of screening every 2 weeks was the most cost-effective strategy across a wide range of willingness to pay thresholds.

Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients.

BACKGROUND: Cytomegalovirus (CMV) infection and disease (CMV episodes) are global concerns after allogeneic hematopoietic stem cell transplantation (HSCT). They affect survival, both by direct and indirect effects. Due to safety issues of current anti-CMV antivirals, long-term CMV prophylaxis is poorly tolerated and the most common strategy to decrease the incidence of CMV disease is preemptive. New, less toxic, molecules are currently being assessed for CMV prophylaxis which should replace or considerably decrease the preemptive approach. The aim of this study was to assess the economic burden of CMV episodes after HSCT with a preemptive approach. METHODS: We analyzed data from 208 consecutive adults transplanted in our institution, between 2008 and 2013. Hospital resource utilization was retrieved via the linked hospital admissions and Diagnostic Related Groups for the period of conditioning to 12 months after transplant. RESULTS: CMV episodes occurred in 70 patients (34%) over the first 12 months following HSCT, after a mean of 75 days (median: 46 (7-334)). The mean total length of stay was significantly associated with the occurrence of a CMV episode (113.9 vs. 87.5 days, p = 0.0002) but was associated neither with the pre-transplant CMV serology of donors/recipients nor with survival. The mean cost of transplant was €104,016 (SD = €37,281) after 12 months. Bivariate and multivariate analyses indicated that the occurrence of >1 CMV episode increased the costs of allogeneic HSCT by 25-30% (p < 0.0001). CONCLUSION: Our study, which is the largest, single-institution cost study of allogeneic HSCT in Europe, shows that two or more CMV episodes significantly increased the transplant cost. New prophylactic strategies to prevent CMV infection and disease should decrease transplant costs.

Cytomegalovirus reactivation posthematopoietic stem cell transplantation (HSCT) and type of graft: A step toward rationalizing CMV testing and positively impacting the economics of HSCT in developing countries.

We aimed to determine a correlation between cytomegalovirus reactivation post hematopoeitic stem cell transplantation (post-HSCT) with the type of graft source, defining children at risk. We analyzed data on children less than 18 years of age undergoing HSCT from 2002 to May 2016 (n = 464). Correlation between reactivation and graft source was analyzed statistically. Reactivation occurred in 3% of children with matched-related donor (MRD) transplants, 33.3% with unrelated peripheral blood stem cells, 17.4% with unrelated cords, and 36.5% (15/41) with mismatched or haploidentical grafts (P = <0.0001). MRD does not warrant weekly PCR, unlike unrelated or haploidentical donors, thus defining protocols for developing countries with limited resources.

Successful Cost-Effective Prevention of Cytomegalovirus Disease in Kidney Transplant Recipients Using Low-Dose Valganciclovir.

OBJECTIVES: Low-dose valganciclovir prophylaxis is still under investigation in renal transplant procedures. Our aim was to assess the cost effectiveness of 450 mg versus 900 mg valganciclovir prophylaxis in kidney transplant recipients. MATERIALS AND METHODS: In this prospective trial, 201 kidney transplant patients were randomized (1:1) to receive 450 mg/d (group 1, n = 100) or 900 mg/d (group 2, n = 101) valganciclovir prophylaxis for the first 6 months after transplant. Patients were studied for incidence of cytomegalovirus disease, leucopenia episodes, rejection episodes, and graft outcomes along with associated costs over 1 year. Costs (in US dollars) of treatment of rejection were also analyzed. RESULTS: Demographic features of the studied groups were comparable. We found that the cost of cytomegalovirus care in group 1 patients was significantly lower (by 50% at 6 months; P < .001), with less leukopenia episodes (P = .04), lower doses of granulocyte colony-stimulating factor (by 30% at 6 months; P = .03), higher doses of mycophenolate mofetil (P = .04), and less rejection episodes (P = .01) compared with group 2. In group 2, there were more episodes of cytomegalovirus infection (P = .052) and BK virus nephropathy (P = .04). Graft and patient outcomes were satisfactory in both groups. CONCLUSIONS: Low-dose valganciclovir for cytomegalovirus prophylaxis after renal transplant is safer, effective and without breakthrough infection, and less costly than using the usual dose.