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      Use of Valacyclovir for the treatment of cytomegalovirus antigenemia after hematopoietic stem cell transplantation

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          Abstract

          Background

          Valacyclovir has been used for prophylaxis against cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT). We investigated the efficacy and safety of high-dose Valacyclovir as pre-emptive therapy in patients with CMV antigenemia after HSCT.

          Methods

          In a retrospective single center study of 61 patients, we compared the rates of viral clearance, recurrent antigenemia and adverse events in patients with pp65 CMV antigenemia who received high dose Valacyclovir (n = 15), Valganciclovir (n = 16), and Foscarnet (n = 30).

          Results

          Overall, 60/61 (98 %) of cases achieved CMV antigenemia clearance by day 28, and no patient developed CMV disease. After adjusting for age, sex, diagnosis, CMV serological status, donor type, CMV antigen level, graft-versus-host disease (GVHD) therapy, and conditioning regimen, there were no significant differences in the rates of viral clearance at day 14 in patients who received Valganciclovir (0.18, 95 % confidence interval (CI) 0.01 to 2.15, p = 0.17) and Foscarnet (OR 0.22, 95 % CI 0.03 to 2.40, p = 0.22), compared with Valacyclovir (assigned OR = 1.00). Recurrent antigenemia by day 180 after clearance of the initial CMV episode occurred in 34/61 (56 %) of patients. Using the multivariate model adjusting for the same covariates, there were also no significant differences in secondary episodes of CMV between treatment groups. With regards to adverse effect monitoring, Foscarnet led to significantly increased creatinine levels ( P = 0.009), while Valganciclovir led to significant decrease in neutrophil counts ( P = 0.012).

          Conclusion

          High dose Valacyclovir is a potential alternative to Valganciclovir and Foscarnet in the stable post-HSCT patient who has cytopenia and is not keen for inpatient treatment of CMV antigenemia.

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          Most cited references20

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          Investigation of CMV disease in immunocompromised patients.

          V Emery (2001)
          Cytomegalovirus (CMV) is a recognised cause of morbidity and mortality in immunocompromised individuals. This review will concentrate on recent advances in the understanding of the complex interplay between the host and parasite and the pathological consequences of perturbation of the host immune system. The classic view of CMV as a slowly replicating virus is challenged by recent in vivo findings suggesting that active replication occurs dynamically in the human host, with a doubling time of approximately one day. In addition, CMV load plays a major role in viral pathogenesis, such that increased CMV replication is a significant risk factor for disease in all immunocompromised groups studied to date. These studies focus attention on understanding the virological and immunological determinants of enhanced viral replication and its pathological consequences.
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            Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants.

            Oral valacyclovir for cytomegalovirus (CMV) prophylaxis in bone marrow transplantation (BMT) was investigated in a randomized, double-blind, acyclovir-controlled, multicenter clinical trial in recipients of allogeneic BMT who were CMV seropositive (or donor positive) before transplantation and were aged 13 years or older. Patients were randomized before BMT. All initially received intravenous acyclovir (500 mg/m(2)) 3 times daily until day 28 after transplantation or after discharge, then oral valacyclovir (2 g) or acyclovir (800 mg) 4 times daily until week 18 after transplantation. Evidence of CMV infection, CMV disease, and death were documented for 22 weeks. Primary end points were time to CMV infection (detection of CMV in blood, broncho-alveolar lavage) or CMV disease and survival. Preemptive CMV therapy was permitted. Seven hundred twenty-seven patients were evaluable for efficacy. After the administration of intravenous acyclovir, valacyclovir was significantly more effective than oral acyclovir in reducing the incidence of CMV infection. CMV infection or disease developed in 102 (28%) valacyclovir patients, compared with 143 (40%) acyclovir patients (HR, 0.59; 95% CI, 0.46-0.76; P <.0001). Survival did not differ between treatments (76% and 75% in the valacyclovir and acyclovir groups, respectively). The safety of oral valacyclovir was similar to that of high-dose oral acyclovir. Valacyclovir was more effective than acyclovir in preventing CMV reactivation in BMT recipients and showed a similar safety profile. CMV disease incidence was low, and no differences were observed between oral valacyclovir and acyclovir. Survival was similar in each group. Valacyclovir prophylaxis provides a clinically valuable intervention but must be part of an overall strategy for CMV prevention in BMT.
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              Valacyclovir: a review of its antiviral activity, pharmacokinetic properties, and clinical efficacy.

              Oral administration of the prodrug valacyclovir results in enhanced bioavailability and significantly greater plasma concentrations of acyclovir than can be achieved with oral doses of acyclovir itself. The results of clinical trials with valacyclovir have demonstrated significant benefits in the resolution of pain associated with herpes zoster infection. Efficacy parameters were similar for valacyclovir and acyclovir in the treatment of herpes simplex; however the results were achieved with lower and less-frequent doses of valacyclovir. The cost of a course of therapy with valacyclovir is expected to be similar to that of other antivirals. The potential clinical benefits of valacyclovir will likely be apparent in the case of acyclovir-resistant herpesvirus infections, where high-dose intravenous treatment with acyclovir has been necessary. Most of these resistant viruses have been encountered in immunocompromised patients, and the resistance has been attributed to inadequate exposure to the drug. Because optimal levels of acyclovir are achieved with a simpler dosing regimen of valacyclovir, compliance may be improved in many patients, thus reducing the incidence of resistant virus.
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                Author and article information

                Contributors
                shinyeu.ong@mohh.com.sg
                ha.truong@sgh.com.sg
                colin.phipps.diong@sgh.com.sg
                yehching.linn@sgh.com.sg
                aloysius.ho.y.l@sgh.com.sg
                goh.yeow.tee@sgh.com.sg
                william.hwang.y.k@sgh.com.sg
                Journal
                BMC Hematol
                BMC Hematol
                BMC Hematology
                BioMed Central (London )
                2052-1839
                19 June 2015
                19 June 2015
                2015
                : 15
                : 8
                Affiliations
                Department of Hematology, Singapore General Hospital, Singapore, Singapore
                Article
                28
                10.1186/s12878-015-0028-2
                4471913
                9b3e7e17-b5ba-46a5-b06a-9691ef00e768
                © Ong et al. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 December 2014
                : 15 May 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

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