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.

Valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus: an economic perspective.

INTRODUCTION: Valganciclovir (vGCV) and valacyclovir (vACV) are used in cytomegalovirus (CMV) prophylaxis in renal transplant recipients. The aim of this study was to compare the economic impact of both regimens during 1-year follow-up. METHODS: A total of 117 renal transplant recipients at risk for CMV were randomized to 3-month prophylaxis either with vGCV (900 mg/day, n = 60) or vACV (8 g/day, n = 57) and their data used in a pharmacoeconomic analysis. The pharmacoeconomic evaluation involved all direct CMV-related expenses in the first year after transplantation. Sensitivity analysis was employed to examine the effects of various prices of antiviral drugs and diagnostic procedures on overall CMV-related costs. Simulation of the more expensive US healthcare perspective was performed, and a scenario involving costs of acute rejection (AR) was examined. RESULTS: Overall CMV-related costs were significantly lower in the vACV arm; median United States dollars (USD) 3473 (3108-3745) vs. USD 5810 (4409-6757; P < 0.001) per patient, respectively. Our data showed that the critical determinant of the major disparity between the prophylactic regimens was the prophylaxis price. Median cost of prophylaxis in the vACV group was USD 1729 (1527-2173) compared to USD 3968 (2683-4857) in the vGCV group (P < 0.001). In sensitivity analysis of the overall CMV-related costs, the least and the most expensive pharmacotherapy and diagnostic scenarios were used; nevertheless, the vACV arm remained markedly less expensive. Simulation considering the higher physician/nurse and hospitalization fees of the US healthcare system and the scenario including expenditure associated with AR episodes also favored vACV. CONCLUSION: VACV prophylaxis for CMV is associated with a significant 44% lower cost than vGCV at the first year after renal transplantation.

Cost analysis in favor of a combined approach for cytomegalovirus after kidney transplantation: a single-center experience.

BACKGROUND: In kidney transplant recipients, cytomegalovirus (CMV) can cause significant morbidity, mortality, and costs, which can be prevented by universal antiviral prophylaxis or preemptive therapy. METHODS: With the aim to improve our understanding of the advantages and disadvantages of these interventions, we documented resource use for 101 consecutive kidney transplant recipients in our center receiving preemptive therapy and estimated resource use for 2 alternative scenarios. RESULTS: At 100 days after transplantation, the mean total costs of our preemptive strategy including monitoring and treatment with intravenous ganciclovir was €2545 per patient. At €4853 per patient, these costs were highest for the CMV-positive donor/CMV-negative recipient (D+/R-) patient subgroup (n = 28), who frequently require recurrent treatment. A treatment scenario with valganciclovir prophylaxis for D+/R- and R+ patients, in which we ignored late-onset disease after discontinuation of prophylaxis, resulted in an estimated cost of €1892 per patient. A combined approach using valganciclovir prophylaxis in the D+/R- group and a preemptive strategy in the R+ groups would result in the lowest mean and median costs per patient (€1701). CONCLUSION: Our study suggests that a combined approach, using valganciclovir prophylaxis in D+/R- patients and preemptive treatment in R+ patients, may result in the lowest cost. This approach seems reasonable as it restricts expensive prophylactic drug therapy to those who would benefit the most, whereas it limits the risk for drug toxicity and late-onset disease in those at lower risk for CMV.

[The evaluation of cost-effectiveness and cost-utility of valganciclovir for the prophylaxis of cytomegalovirus disease to 200 days after kidney transplantation]. / Ocena kosztowej efektywnosci i kosztowej uzytecznosci stosowania walgancyklowiru w profilaktyce wystapienia choroby cytomegalowirusowej do 200. dnia od przeszczepu nerki.

UNLABELLED: Standard procedure for cytomegalovirus disease (CMV) prophylaxis in kidney transplant patients was the administration of valganciclovir for up to 110 days after organ transplant. This prophylaxis has been extended up to 200 days in Poland since 2011. The decision was based on the results of clinical trials which showed significant clinical benefit in case of prolonged administration of the drug. The aim of the analysis was to provide the economic evaluation of extending the CMV prophylaxis with co-financed from public funds Valcyte (valganciclovirum; 60 tab. a 450 mg; Roche Polska Sp. z o.o.) from 110 to 200 days, in the high risk patients group after kidney transplant (seronegative recipient and infected donor, D+/R-). The analysis was performed from the Polish healthcare payer's perspective. MATERIAL AND METHODS: All methods used in the following study were consistent with the Requirements of the Polish HTA Agency (AHTAPOL). The cost-effectiveness and the cost-utility analysis were performed on the basis of a randomised study which was identified as a result of the systematic search of the medical databases, comparing 200 days valgancyclovir administration with 100 days drug use as a prophylaxis of CMV disease in the patients group mentioned above. The Markov model was developed, simulating the disease evolution over time considering a high risk patient after kidney transplant treated with valgancicloviras the CMV disease prophylaxis. The disease period was divided into health states that are the most probable for this condition and the transitions probabilities between them were identified and assigned. Based on the clinical trial results, registry database of health conditions usability and experts' opinion, all health states (i.e. death, kidney transplant, CMV disease) were attributed with utilities and costs. The direct costs, important from the Polish healthcare payer's perspective, were included in the analysis. Extension of the proposed model in the series of one month time cycles made it possible to assess long-term (assumed time horizon was median patient's life expectancy--23,5 years) costs and clinical effects of the compared technologies. RESULTS: The Incremental Cost-Effectiveness Ratio (ICER) was 39 669 008 PLN and The Incremental Cost-Utility Ratio (ICUR) was 48 008 PLN in the specified time horizon. The result is well below the accepted threshold of profitability in Poland (assuming tripled GDP per capita cost-utility threshold, i.e. 99 543 PLN), which means that the therapy is cost-effective. CONCLUSIONS: The results of the analysis confirmed that the 200 days use of valganciclovirin the prevention of CMV disease compared to standard 110 days therapy is economically justified from the Polish healthcare payer's perspective.

Intravitreal ganciclovir maintenance injection for cytomegalovirus retinitis: efficacy of a low-volume, intermediate-dose regimen.

OBJECTIVE: To report the clinical outcomes of highly active antiretroviral therapy (HAART)-naïve, human immunodeficiency virus (HIV)-positive patients with newly diagnosed cytomegalovirus (CMV) retinitis receiving intravitreal injections of a low-volume intermediate maintenance dose (1.0 mg/0.02 ml) of ganciclovir. DESIGN: Nonrandomized, retrospective, interventional series. PARTICIPANTS: A consecutive cohort of 34 eyes from 24 HAART-naïve patients with AIDS and diagnosed with CMV retinitis by retinal specialists at the Singapore Communicable Disease Centre. INTERVENTION: Patients received a maintenance dose of 1.0 mg/0.02 ml of intravitreal ganciclovir once weekly after standard induction therapy with 2.0 mg/0.04 ml of twice weekly intravitreal ganciclovir. MAIN OUTCOME MEASURES: Time to progression, visual acuity, and complications. Progression was observed using photographic documentation. RESULTS: The median time to progression was 152 days (mean, 380.1 days, 95% confidence interval, 240.8-519.4). The median follow-up was 95 days (mean, 207.9 days). Three eyes developed rhegmatogenous detachments, but there was no endophthalmitis after 1858 injections. Contralateral involvement of CMV retinitis occurred in 17.6% of the patients. The cost estimate for intravitreal injections over a 6-month period was 11.7% that of sustained-release implants for unilateral treatment and 11.1% that of daily continuous intravenous infusions and oral valganciclovir compared with bilateral treatments. CONCLUSIONS: Weekly low-volume, intermediate-dose (1.0 mg/0.02 ml) ganciclovir is an efficacious option in developing countries where newer options of sustained-release implants and oral valganciclovir are unavailable or prohibitively expensive. The regimen maintains a long time to progression, preserving vision while minimizing retinal toxicity complications.

Pharmacoeconomic impact of different regimens to prevent cytomegalovirus infection in renal transplant recipients.

BACKGROUND: The aim of this study was to determine the cost impact of four different strategies for prevention of cytomegalovirus (CMV) disease after renal transplantation. METHODS: Hospitalization data and medical resource utilization data were prospectively collected alongside two randomized trials. In the first trial, the patients were randomized to 3-month prophylaxis with either oral ganciclovir (1 g t.i.d., n = 36) or valacyclovir (2 g q.i.d., n = 35), and to the control group (n = 12) managed by deferred therapy. In the second trial, the patients were randomly assigned to 3-month valacyclovir prophylaxis (n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia. The cost analysis involved all real costs directly related to CMV during the first year after renal transplantation. RESULTS: The mean CMV-associated costs per patient were EUR 4,581, 2,577, 4,968, and 8,050 in patients in the ganciclovir, valacyclovir, preemptive, and deferred therapy groups, respectively (p < 0.001). Valacyclovir prophylaxis was significantly less expensive than any other regimen. The cost of one episode of CMV disease was EUR 7,510 per patient. Due to excessive incidence of CMV disease, deferred therapy was the most expensive strategy (p < 0.001). CONCLUSIONS: Valacyclovir prophylaxis is less expensive strategy compared with any other regimen.

Six-month prophylaxis is cost effective in transplant patients at high risk for cytomegalovirus infection.

The risk of late-onset cytomegalovirus (CMV) infection remains a concern in seronegative kidney and/or pancreas transplant recipients of seropositive organs despite the use of antiviral prophylaxis. The optimal duration of prophylaxis is unknown. We studied the cost effectiveness of 6- versus 3-mo prophylaxis with valganciclovir. A total of 222 seronegative recipients of seropositive kidney and/or pancreas transplants received valganciclovir prophylaxis for either 3 or 6 mo during two consecutive time periods. We assessed the incidence of CMV infection and disease 12 mo after completion of prophylaxis and performed cost-effectiveness analyses. The overall incidence of CMV infection and disease was 26.7% and 24.4% in the 3-mo group and 20.9% and 12.1% in the 6-mo group, respectively. Six-month prophylaxis was associated with a statistically significant reduction in risk for CMV disease (HR, 0.35; 95% CI, 0.17 to 0.72), but not infection (HR, 0.65; 95% CI, 0.37 to 1.14). Cost-effectiveness analyses showed that 6-mo prophylaxis combined with a one-time viremia determination at the end of the prophylaxis period incurred an incremental cost of $34,362 and $16,215 per case of infection and disease avoided, respectively, and $8,304 per one quality adjusted life-year gained. Sensitivity analyses supported the cost effectiveness of 6-mo prophylaxis over a wide range of valganciclovir and hospital costs, as well as variation in the incidence of CMV disease. In summary, 6-mo prophylaxis with valganciclovir combined with a one-time determination of viremia is cost effective in reducing CMV infection and disease in seronegative recipients of seropositive kidney and/or pancreas transplants.

Valacyclovir prophylaxis versus preemptive valganciclovir therapy to prevent cytomegalovirus disease after renal transplantation.

Both preemptive therapy and universal prophylaxis are used to prevent cytomegalovirus (CMV) disease after transplantation. Randomized trials comparing both strategies are sparse. Renal transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to 3-month prophylaxis with valacyclovir (2 g q.i.d., n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia (>/=2000 copies/mL by quantitative PCR in whole blood) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. The 12-month incidence of CMV DNAemia was higher in the preemptive group (92% vs. 59%, p < 0.001) while the incidence of CMV disease was not different (6% vs. 9%, p = 0.567). The onset of CMV DNAemia was delayed in the valacyclovir group (37 +/- 22 vs. 187 +/- 110 days, p < 0.001). Significantly higher rate of biopsy-proven acute rejection during 12 months was observed in the preemptive group (36% vs. 15%, p = 0.034). The average CMV-associated costs per patient were $5525 and $2629 in preemptive therapy and valacyclovir, respectively (p < 0.001). However, assuming the cost of $60 per PCR test, there was no difference in overall costs. In conclusion, preemptive valganciclovir therapy and valacyclovir prophylaxis are equally effective in the prevention of CMV disease after renal transplantation.

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.

Economic evaluation of treatment administration strategies of ganciclovir for cytomegalovirus retinitis in HIV/AIDS patients in Thailand: a simulation study.

BACKGROUND: There are many effective interventions, via various routes (intravenous [IV], oral [OR], intravitreal injection [IVT] and intraocular implantation [IMP]), for treating cytomegalovirus retinitis (CMVR) that have become available. There are large variations in treating CMVR in clinical practice in Thailand. OBJECTIVE: To evaluate the incremental cost-effectiveness ratio (ICER) of providing (i) IVT, (ii) IV/OR and (iii) IMP ganciclovir to patients with HIV/AIDS and CMVR versus providing no treatment. DESIGN: A simulation study for which the input parameters were derived from a systematic review of the literature, a hospital-based survey and patient interviews. SETTING: The analysis assumed a Thai healthcare system perspective. However, the model was run using both societal and healthcare provider perspectives. RESULTS: Our results suggest that IVT ganciclovir was cost effective and the best option for treating patients with CMVR irrespective of whether patients received antiretroviral treatment (ART). In patients receiving ART, moving from IVT to IV/OR ganciclovir was also likely to be a cost-effective option. Offering IMP ganciclovir was not likely to be cost effective. Providing treatments for patients with bilateral CMVR was more cost effective than providing treatments for those with unilateral CMVR, and offering treatments for patients receiving ART was better value for money than treating patients without ART. CONCLUSIONS: Our models suggest that IV/OR ganciclovir should be recommended for the treatment of unilateral and bilateral CMVR for patients receiving ART in the Thai healthcare system. IVT ganciclovir may also have a role in the treatment of CMVR patients not receiving ART.

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.

Effectiveness of Preemptive Therapy for Cytomegalovirus Disease in Pediatric Liver Transplantation.

BACKGROUND: Most pediatric liver transplantation (LT) centers administer long courses of prophylaxis against cytomegalovirus (CMV) without evidence of benefit and with significant drug exposure and costs. We aimed at evaluating overall outcomes, direct and putative indirect effects of CMV, possible impact of viremia and risk factors for CMV infection in pediatric LT recipients managed with ganciclovir-based preemptive therapy (PET). METHODS: The records of all the children who underwent LT between 2008 and 2014 were retrospectively analyzed. RESULTS: One hundred children were included. Three children had CMV disease; no CMV-related death or graft loss was recorded. The only identified risk factor for CMV infection was the donor/recipient serostatus (odds ratio, 17.23; 95% confidence interval, 1.88-157.87; P = 0.012), while viremia per se did not worsen LT outcomes, such as the incidence of acute rejection, Epstein-Barr virus infection, sepsis, biliary and vascular complications, nor graft dysfunction/loss or death at 3 and 5 years after LT. When compared with a historical cohort of children receiving ganciclovir prophylaxis, PET did not differ from prophylaxis for any of the selected outcomes, but was rather associated with lower antiviral drug exposure (6.4 ± 13 days vs 38.6 ± 14 days, P < 0.0001) and cost per patient (2.2 ± 3.9 k&OV0556; vs 6.6 ± 8.2 k&OV0556;, P = 0.001). CONCLUSIONS: PET is effective in controlling CMV in children receiving LT, with lower costs and lower exposure to antivirals.

Cost-effectiveness of cytomegalovirus (CMV) disease prevention in patients with AIDS: oral ganciclovir and CMV polymerase chain reaction testing.

OBJECTIVE: To perform a cost-effectiveness analysis of strategies to prevent cytomegalovirus (CMV) disease. METHOD: Markov model and published data. PATIENTS: Hypothetical HIV-infected patients with CD4 cell counts < or = 50 x 10(6)/l and positive CMV serologies. INTERVENTIONS: Oral ganciclovir daily versus plasma CMV DNA polymerase chain reaction (PCR) testing every 3 months with oral ganciclovir for patients with positive tests. OUTCOME MEASURES: The number of CMV disease cases prevented by the interventions, life expectancy, disease-free life expectancy, and the cost to extend life by 1 year. RESULTS: Oral ganciclovir preventive therapy reduces the lifetime number of CMV disease cases by 50 per 1000 cohort, extends life expectancy by 5 days and disease-free life expectancy by 18 days, and costs US$ 1,762,517 per year of life extended. Periodic PCR testing reduces the lifetime number of CMV disease cases by eight per 1000 cohort, extends life expectancy by 1 day and disease-free life expectancy by 3 days, and costs US$ 495,158 per year of life extended. The prevention strategies could be acceptably cost effective only under a combination of optimistic assumptions and reduced costs. CONCLUSIONS: Oral ganciclovir preventive therapy and periodic plasma testing for CMV PCR with oral ganciclovir for those with positive tests result in small benefits at great cost. They are not cost-effective prevention strategies for persons with advanced HIV infection and positive CMV serologies.

The economic impact of cytomegalovirus infection after liver transplantation.

BACKGROUND: We studied the economic impact of cytomegalovirus (CMV) disease and its effective reduction with antiviral prophylaxis in liver transplant recipients. METHOD: Analysis of institutional charge data accumulated during a prospective, randomized, controlled trial comparing oral acyclovir 800 mg four times daily for 120 days (ACV) and intravenous ganciclovir 5 mg/kg every 12 h for 14 days followed by ACV for 106 days (GCV) was performed. RESULTS: Liver transplant recipients who developed CMV disease had significantly higher charges (median: $148,300) than those who developed asymptomatic CMV infection ($119,600) or experienced no CMV infection ($114,100) (P<0.01). A multiple linear regression analysis indicated that CMV disease is associated with a 49% increase in charges, independent of other factors influencing increased hospitalization charges. In CMV-seronegative patients who received a CMV-seropositive donor organ, GCV prophylaxis was associated with a significant reduction in charges, as compared to ACV prophylaxis ($113,900 vs. $153,300, respectively; P=0.02). CONCLUSIONS: CMV disease is an independent risk factor for increased resource utilization associated with liver transplantation. The use of an effective prophylactic antiviral regimen provides savings in health care resources, particularly in patients at high risk for developing CMV disease.

Cytomegalovirus antigenemia directed pre-emptive prophylaxis with oral versus I.V. ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, controlled trial.

BACKGROUND: The efficacy of pre-emptively administered oral ganciclovir in preventing cytomegalovirus (CMV) disease has not been documented in liver transplant recipients. We sought to compare the efficacy of pre-emptive oral ganciclovir with that of i.v. ganciclovir for the prevention of CMV disease after liver transplantation, and to determine whether withholding prophylaxis in the absence of CMV antigenemia, reliably identified patients in whom no prophylaxis was necessary. METHODS: Surveillance cultures for CMV pp65 antigenemia were performed in all patients at weeks 2, 4, 6, 8, 12, and 16. Patients with CMV antigenemia were randomized into two study groups. The experimental group received oral ganciclovir for 6 weeks (2 g t.i.d. for 2 weeks, then 1 g t.i.d. for 4 weeks), and the control group received i.v. ganciclovir (5 mg/kg q 12 hr) for 7 days. RESULTS: Of 72 consecutive liver transplant recipients studied, CMV antigenemia occurred in 31% (22 of 72). Twenty-two patients with asymptomatic antigenemia were randomized to two study groups. CMV disease (viral syndrome) occurred in 9% (1 of 11) of the patients in the i.v. ganciclovir group and in 0% (0 of 11) of the patients in the oral ganciclovir group. None of the study patients developed tissue invasive CMV disease. The median reduction in antigenemia level with oral ganciclovir was 55% at week 1, and 100% at week 2. Overall, 64% of the patients by week 1, 93% by week 2, and 100% by week 4 had antigenemia levels below the baseline after oral ganciclovir. Of 50 patients without CMV antigenemia, none developed CMV disease. CONCLUSIONS: Pre-emptive prophylaxis based on CMV antigenemia can effectively target the patients for CMV prophylaxis; 69% of the patients never received antiviral prophylaxis and did not develop CMV disease. Antiviral therapy instituted upon detection of antigenemia prevented tissue invasive CMV in both ganciclovir groups. Pre-emptively administered oral ganciclovir was effective as prophylaxis for CMV disease after liver transplantation.

Efficacy and cost effectiveness of oral ganciclovir in the prevention of cytomegalovirus disease after lung transplantation.

BACKGROUND: Cytomegalovirus is the single most frequent pulmonary pathogen in lung transplant recipients who survive at least 2 weeks. Patients at increased risk are either seropositive or have received an allograft from a donor with latent infection. Morbidity and mortality caused by cytomegalovirus disease is still considerably high. METHODS: In an open, comparative study, we evaluated the efficacy, tolerance, and cost effectiveness of postoperative ganciclovir prophylaxis: intravenous dose of 2x5 mg/kg/day for 14 days, followed by either intravenous doses of 5 mg/kg]day (five patients), or oral doses of 3x 1000 mg (nine patients) up to 90 days. Oral ganciclovir was continued until prednisone was tapered below 15 mg/day. Prophylaxed groups were compared with a historical control (eight patients) in respect to cytomegalovirus disease, in-hospital stay, overall costs, and survival. Follow-up times and the net state of immunosuppressive therapy between groups were comparable. RESULTS: Six (75%) of the non-prophylaxed patients developed cytomegalovirus disease compared to none in the intravenous and one in the oral ganciclovir group (P=0.013). The non-prophylaxed patients had a longer cytomegalovirus-related in-hospital stay (P=0.018) and nonsignificantly higher cytomegalovirus-related costs. Bronchiolitis obliterans syndrome was less frequent with prophylaxis (P=0.039), and survival tended to be better (P=0.072). The only adverse effect was a subclavian vein thrombosis in the intravenous ganciclovir group. CONCLUSIONS: In lung transplant recipients, ganciclovir prophylaxis, either intravenous or oral, is safe, well tolerated, and effective in preventing cytomegalovirus disease. Moreover, ganciclovir prophylaxis seems likely to reduce the incidence of bronchiolitis obliterans syndrome. The oral formulation might be preferable because its convenience and possibly lower costs.

Costs and outcomes of prolonged cytomegalovirus prophylaxis to cover the enhanced immunosuppression phase following lung transplantation.

BACKGROUND: Cytomegalovirus (CMV) disease is one of the major challenges of lung transplantation that may determine outcome. The benefits of ganciclovir prophylaxis seem indisputable, but no consensus has been reached on the optimal duration of therapy. Results with different protocols suggest that efficacy is related to the duration of treatment. MATERIALS AND METHODS: To evaluate the additional effect of a prolonged regimen throughout the maximal immunosuppression phase, we conceived a protocol administering ganciclovir, 5 mg/kg/d for 20 weeks from the first postoperative day, to all CMV-seropositive patients undergoing lung transplantation or receiving the lung from a seropositive donor. Virus shedding was routinely measured in body fluids including through BAL. Costs and outcomes are compared with those in shorter prophylaxis protocols from previous reported studies. RESULTS: Of 30 lung transplant recipients, 22 patients at risk for CMV reactivations were observed for (mean SD) 22.9 +/- 13.2 months. CMV infections were detected in eight patients 8.6 +/- 5.1 months after transplantation. CMV pneumonitis developed in one patient 9 months following the transplant event. Prolonged IV ganciclovir prophylaxis was, in general, well tolerated. However, five patients had bacteremia and one had a local thrombosis, with no long-term consequences. A prescription for 8 additional weeks of prophylaxis to cover the whole period of enhanced immunosuppression decreased the cumulative incidence of first CMV infections by 29% 1 year after transplantation compared to 12-week regimens reported in other studies that indicated a 50% reduction in the incidence of first CMV infection. The total cost of 20 weeks of IV ganciclovir prophylaxis was $6,010 (US dollars) per patient more expensive than 12 weeks of IV ganciclovir therapy. This was not offset by the reduced requirement for treatment of infections. Indeed, extrapolating to our cohort of patients, the additional cost per patient was seven times greater than the treatment for the infections that were reported after the 12-week prophylaxis protocol. CONCLUSION: Prolonging ganciclovir prophylaxis to 20 weeks decreased by half the rates of CMV infection when compared to reports from centers using a shorter protocol of 12 weeks for ganciclovir prophylaxis. Additionally, a delay in the onset of the first infection was observed. Nevertheless, the increase in costs and the discomfort of long-term use of venous catheters are important factors that may favor a shorter regimen of 12 weeks followed by preemptive therapies each time CMV infections occur.

Comparison of intravenous ganciclovir and cytomegalovirus hyperimmune globulin pre-emptive treatment in cytomegalovirus-positive heart transplant recipients.

BACKGROUND: We compared the use of intravenous ganciclovir and cytomegalovirus hyperimmune globulin (CMVIG) as a pre-emptive treatment for cytomegalovirus (CMV)-positive heart transplant recipients. METHODS: Of 59 CMV-seropositive adult heart transplant recipients enrolled in Group 1, 37 tested positive for pp65 antigen within 12 weeks post-transplantation. These patients were randomized to receive either intravenous ganciclovir (n = 23) or CMVIG (n = 14). Group 2 included 133 CMV-seropositive heart transplant recipients who were not tested for CMV antigenemia and who received no anti-CMV therapy. RESULTS: CMV disease developed in 0 of 59 patients from Group 1, and in 27 of 133 patients (20%) in Group 2 (p = 0.0001). The incidence of superinfections was lower in Group 1 (0.28 +/- 0.46) than in Group 2 (1.10 +/- 1.33) (p = 0.01). The 2 groups did not differ with regard to incidence of rejection (0.7 +/- 0.9 in Group 1 vs 1.0 +/- 1.2 in Group 2; p = NS), transplant coronary artery disease at 1 year (14% in Group 1 vs 16% in Group 2; p = NS) or post-transplant lymphoproliferative disease (0% in Group 1 vs 2% in Group 2; p = NS). Ganciclovir and CMVIG therapies were associated with similar rates of rejection (0.52 +/- 0.6 with ganciclovir vs 0.50 +/- 0.60 with CMVIG; p = NS), superinfection (0.30 +/- 0.48 with ganciclovir vs 0.25 +/- 0.46 with CMVIG; p = NS), and transplant coronary artery disease at 1 year (13% with ganciclovir vs 14% with CMVIG, p = NS). CONCLUSIONS: The pre-emptive anti-CMV approach is superior to prophylaxis in CMV-seropositive heart transplant recipients. Both ganciclovir and CMVIG are equally effective.

Comparison of the efficacy and cost effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients.

BACKGROUND: CMV disease remains a major complication of lung transplantation and attempts to prevent it have met with marginal success. In a previous study we documented that universal prophylaxis did not prevent CMV disease but merely delayed it, and was very costly. METHODS: We compared the efficacy and cost of pre-emptive therapy with ganciclovir, guided by CMV antigenemia, to that of historic controls that received universal prophylaxis with ganciclovir. CMV antigenemia assay was done routinely and pre-emptive therapy was initiated if greater than 25 CMV positive cells per 100,000 polymorphonuclear cells were found. RESULTS: Nineteen patients were enrolled; 6 of of whom received 12 courses of pre-emptive therapy. The incidence of CMV disease was 26% compared to 38% for the historical controls (p = 0.51). None of the patients that received pre-emptive therapy developed CMV disease following that therapy. Antigenemia failed to predict disease in 5 patients that developed it, and thus it is unknown if pre-emptive therapy could have prevented it. There was no mortality in either the study patients or historic controls directly related to CMV. The net savings with pre-emptive therapy was $2569 per patient. CONCLUSIONS: We conclude that pre-emptive therapy with ganciclovir is as safe and effective as universal prophylaxis in preventing CMV disease in lung transplant recipients, and is less expensive. The appropriate surveillance technique and timing remain to be determine to optimize the efficacy of pre-emptive therapy.

Prophylaxis of primary cytomegalovirus disease in renal transplant recipients. A trial of ganciclovir vs immunoglobulin.

OBJECTIVE: To compare the efficacy, safety, and cost of prophylactic low-dose ganciclovir with that of immunoglobulin in renal transplant recipients at risk for primary cytomegalovirus (CMV) disease. DESIGN AND SETTING: A prospective, randomized trial at a 650-bed tertiary medical center hospital. PATIENTS: Fifty-one consecutive CMV-seronegative patients who received renal allografts from seropositive donors between March 1990 and April 1992. MAIN OUTCOME MEASURES: Patient and allograft survival, and the incidence and severity of CMV disease. INTERVENTION: Cytomegalovirus prophylaxis with seven doses of intravenous immunoglobulin for 6-week periods (group 1, n = 27) or low-dose intravenous ganciclovir for 3 weeks (group 2, n = 24). Results were compared with those obtained in 23 CMV-seronegative historical controls who received renal allografts from CMV-seropositive donors between 1987 and 1989, and who did not receive prophylaxis for CMV (group 3). RESULTS: Both prophylactic regimens significantly reduced the incidence of invasive CMV infection (P < .05) and were well tolerated. However, the cost of ganciclovir ($350 per patient) was substantially less than that of immunoglobulin ($4000 per patient). CONCLUSIONS: These data suggest that prophylactic ganciclovir therapy provides a cost-effective approach toward significantly improving the outcome of renal transplantation in recipients at risk for primary CMV disease.