valacyclovir and Cytomegalovirus-Infections

Congenital human cytomegalovirus (CMV) infection is the most common congenital infection, affecting around 1 in 200 infants in high-income settings. It can have life-long consequences for up to one in four children, including sensorineural hearing loss and neurodisability. Despite the frequency of congenital CMV and the severity for some children, it is a little-known condition by pregnant women, families and healthcare providers. Timely diagnosis of CMV infection in pregnancy is important to facilitate consideration of treatment with valaciclovir, which may reduce the risk of transmission to the fetus or reduce the severity of the outcomes for infected infants. Recognition of features of congenital CMV is important for neonatologists, paediatricians and audiologists to prompt testing for congenital CMV within the first 21 days of life. Early diagnosis gives the opportunity for valganciclovir treatment, where appropriate, to improve outcomes for affected infants. Further research is urgently needed to inform decisions about antenatal and neonatal screening, long-term outcomes for asymptomatic and symptomatic infants, predictors of these outcomes and optimal treatment for women and infants.

Topics: Child; Cytomegalovirus Infections; Female; Fetal Diseases; Hearing Loss, Sensorineural; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Valacyclovir; Valganciclovir

Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal therapy. The role of valacyclovir therapy in reducing the risk of vertical transmission, symptomatic congenital CMV infection and adverse outcome is controversial. The main aim of this systematic review and meta-analysis was to investigate the safety and effectiveness of prenatal valacyclovir therapy in pregnancies with maternal CMV infection.. MEDLINE, EMBASE and Cochrane databases and ClinicalTrials.gov were searched. The inclusion criteria were pregnancy with confirmed maternal CMV infection, treated or untreated with valacyclovir. The primary outcome was the incidence of congenital CMV infection confirmed by a positive CMV polymerase chain reaction result of the amniotic fluid. The secondary outcomes were symptomatic and asymptomatic infection, perinatal death, termination of pregnancy, anomalies detected on follow-up ultrasound, on fetal magnetic resonance imaging or at birth, severe and mild-to-moderate symptoms due to congenital CMV infection, neurological, visual and hearing symptoms, and adverse events related to valacyclovir. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) or Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool, as appropriate. Head-to-head meta-analyses were used to compare the risk of each of the explored outcomes according to whether pregnancies with maternal CMV infection were treated with prenatal valacyclovir therapy.. Eight studies (620 women) were included. Pregnancies treated with valacyclovir had a significantly lower risk of congenital CMV infection compared with those not receiving valacyclovir (three studies; 325 fetuses; pooled odds ratio (OR), 0.37 (95% CI, 0.21-0.64); I. Prenatal valacyclovir administration in pregnancies with maternal CMV infection reduces the risk of congenital CMV infection. Further evidence is needed to elucidate whether valacyclovir can affect the course of infection in the fetus and the risk of symptomatic fetal or neonatal infection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Topics: Amniotic Fluid; Cytomegalovirus Infections; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Perinatal Death; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Valacyclovir

Cytomegalovirus (CMV) is the most common cause of congenital infections in developed countries because is capable of infecting the fetus after both primary and recurrent maternal infection, and because the virus may be spread for years through infected children. Moreover, CMV is the most serious congenital infection associated with severe neurological and sensorineural sequelae, which can occur at birth or develop later on. Hygienic measures can prevent CMV transmission, which mainly involve contact with children under 3 years of age and attending a nursery or daycare. In animal and human pregnancies, many observational and controlled studies have shown that CMV-specific hyperimmune globulin (HIG) is safe and can significantly decrease maternal-fetal transmission of CMV infection and, mostly, the occurrence of CMV disease. Recently, valaciclovir at the dosage of 8 g/day was also reported to be capable of decreasing the rates of congenital infection and disease. However, comparing the results of our two recent case series, the infants born to women treated with HIG showed significantly lower rates of CMV DNA positivity in urine (9.7% vs. 75.0%;

Topics: Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Female; Fetal Diseases; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Valacyclovir

Many antiviral agents have been studied in clinical trials for allograft rejection prevention following cytomegalovirus (CMV) prophylaxis in high-risk kidney transplant patients. However, data on the most effective and safest treatment are lacking. We conducted a systematic review and network meta-analysis to rank CMV prophylaxis agents for allograft rejection prevention following CMV prophylaxis in high-risk kidney transplant patients according to their efficacy and safety. We conducted searches on the MEDLINE, Embase, SCOPUS, and CENTRAL databases, as well as the reference lists of selected studies up to December 2021, for published and peer-reviewed randomized controlled trials assessing the efficacy of CMV prophylaxis agents in high-risk kidney transplant patients. Thirteen studies were independently selected by three reviewers and included post-kidney transplant patients indicated for CMV prophylaxis who had been randomized to receive prophylactic antiviral agents or standard of care. The reviewers independently extracted data from the included studies, and direct and network meta-analyses were applied to assess the study outcomes. The probability of efficacy and safety was evaluated, and the drugs were assigned a numerical ranking. We evaluated the risk of bias using the Cochrane Risk of Bias 2.0 tool. The primary outcome was an incidence of biopsy-proven acute rejection, whereas the secondary outcome was a composite of major adverse drug reactions. Each outcome referred to the definition provided in the original studies. Valganciclovir, valacyclovir, and ganciclovir were identified to significantly decrease the incidence of biopsy-proven acute rejection with pooled risk differences (RDs) of -20.53% (95% confidence interval [CI] = -36.09% to -4.98%), -19.3% (95% CI = -32.7% to -5.93%), and -10.4% (95% CI = -19.7% to -0.12%), respectively. The overall major adverse drug reaction was 5.7% without a significant difference when compared with placebo. Valganciclovir had the best combined efficacy and safety among the examined antiviral agents and was the most effective and safest antiviral agent overall for allograft rejection prevention following CMV prophylaxis. Valacyclovir was the optimal alternative antiviral agent for patients who were unable to tolerate intravenous ganciclovir or access oral valganciclovir as financial problem. However, compliance and dose-related toxicities should be closely monitored.

Topics: Allografts; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Network Meta-Analysis; Randomized Controlled Trials as Topic; Valacyclovir; Valganciclovir

Cytomegalovirus (CMV) is the leading infectious cause of congenital neurological disabilities. Valacyclovir and CMV hyperimmune globulin (HIG) may reduce vertical transmission and sequelae in neonates. A systematic review on valacyclovir and CMV HIG in preventing vertical transmission or reducing sequelae in neonates was conducted to 3 September 2021. Valacyclovir as a preventive strategy was supported by a well-conducted randomized controlled trial. Evidence supporting valacyclovir as a treatment strategy was limited to observational studies at moderate risk of bias. CMV HIG was not supported as a preventive strategy in 2 randomized controlled trials, which contrasted with observational studies. Evidence favoring CMV HIG as a treatment strategy was limited to observational studies at moderate risk of bias. The role of valacyclovir and CMV HIG in CMV infection in pregnancy is still being defined. Valacyclovir to prevent vertical transmission has the highest quality evidence in favor of use.

Topics: Cytomegalovirus; Cytomegalovirus Infections; Female; Fetal Diseases; Globulins; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic; Valacyclovir

Cytomegalovirus (CMV) is the most common viral cause of congenital infection, occurring in approximately 1-2% of live births worldwide. Given our increasing knowledge of risk, advances in the identification of maternal infection, and the extremely limited options for the treatment of fetal infection, the prevention is a promising direction for research efforts. Recently, there have been several exciting studies assessing different ways of preventing congenital infection in the fetus and one in particular has focused on the use of valaciclovir.. A recent study reported a 71% reduction in vertical transmission of CMV with the use of oral valaciclovir following maternal primary CMV infection early in pregnancy. The clinical impact of this study could be enormous and it has particular implications for considerations around maternal serological screening in the first trimester of pregnancy. Further research assessing behaviour modifications during early pregnancy could also provide evidence for an effective primary prevention technique.. Prevention of congenital CMV infection, whether primary, secondary or tertiary, is possible, however, there are barriers to its utilisation in a clinical setting. The main limitation is the requirement for early, effective and large-scale serological screening of mothers to detect asymptomatic primary infection.

Topics: Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Valacyclovir

Cytomegalovirus is the most common congenital infection, affecting 0.5-2% of all live births and the main nongenetic cause of congenital sensorineural hearing loss and neurological damage. Congenital cytomegalovirus can follow maternal primary infection or nonprimary infection. Sensorineurological morbidity is confined to the first trimester with up to 40-50% of infected neonates developing sequelae after first-trimester primary infection. Serological testing before 14 weeks is critical to identify primary infection within 3 months around conception but is not informative in women already immune before pregnancy. In Europe and the United States, primary infection in the first trimester are mainly seen in young parous women with a previous child younger than 3 years. Congenital cytomegalovirus should be evoked on prenatal ultrasound when the fetus is small for gestation and shows echogenic bowel, effusions, or any cerebral anomaly. Although the sensitivity of routine ultrasound in predicting neonatal symptoms is around 25%, serial targeted ultrasound and magnetic resonance imaging of known infected fetuses show greater than 95% sensitivity for brain anomalies. Fetal diagnosis is done by amniocentesis from 17 weeks. Prevention consists of both parents avoiding contact with body fluids from infected individuals, especially toddlers, from before conception until 14 weeks. Candidate vaccines failed to provide more than 75% protection for >2 years in preventing cytomegalovirus infection. Medical therapies such as cytomegalovirus hyperimmune globulins aim to reduce the risk of vertical transmission but 2 randomized controlled trials have not found any benefit. Valaciclovir given from the diagnosis of primary infection up to amniocentesis decreased vertical transmission rates from 29.8% to 11.1% in the treatment group in a randomized controlled trial of 90 pregnant women. In a phase II open-label trial, oral valaciclovir (8 g/d) given to pregnant women with a mildly symptomatic fetus was associated with a higher chance of delivering an asymptomatic neonate (82%), compared with an untreated historical cohort (43%). Valganciclovir given to symptomatic neonates is likely to improve hearing and neurological symptoms, the extent of which and the duration of treatment are still debated. In conclusion, congenital cytomegalovirus infection is a public health challenge. In view of recent knowledge on diagnosis and pre- and postnatal management, health care providers shoul

Topics: Cytomegalovirus Infections; Female; Fetal Diseases; Hearing Loss, Sensorineural; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Magnetic Resonance Imaging; Nervous System Diseases; Preconception Care; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Prenatal Diagnosis; Serologic Tests; Ultrasonography, Prenatal; Valacyclovir

Congenital CMV is the most common congenital infection in the developed world. Infection results in congenital disease ranging from asymptomatic infection to severe neurodevelopmental impairment, and occasionally fetal or neonatal death. Fetal infection can occur through maternal-fetal transmission during primary maternal infection or maternal reactivation or re-infection. Awareness among maternal health care providers and parents is low. The prevention of maternal CMV infection currently relies on hygiene measures, with no effective CMV vaccine or prophylactic therapies. No licensed treatment options are available to prevent maternal-fetal transmission or fetal disease. Hyperimmunoglobulin and valaciclovir have been investigated for prevention of maternal-fetal transmission or fetal treatment, with some evidence supporting consideration of maternal administration of hyperimmunoglobulin or valaciclovir therapy in certain circumstances. This article outlines the clinical evidence regarding proven preventative behavioral measures and experimental hyperimmunoglobulin and valaciclovir therapies, that is structured around common questions asked by pregnant women about CMV infection. It is aimed to help maternity health care providers counsel prospective parents about congenital CMV disease and the preventative and therapeutic strategies currently available.

Topics: Antiviral Agents; Cytomegalovirus Infections; Female; Fetal Therapies; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Prenatal Diagnosis; Valacyclovir

Congenital cytomegalovirus (CMV) infection is the leading infectious cause of neurological impairment for which, currently, there are no approved antenatal treatment options.. The aim of this article was to summarize the available evidence on the use of valacyclovir during pregnancy to prevent and treat congenital CMV infection and disease.. Two databases (PubMed and ClinicalTrial.gov) were reviewed.. Six relevant documents were identified, namely one observational study, three clinical trials, two case reports. Most relevant findings were those from two clinical trials. A phase 2/3 placebo-controlled study showed a decrease of 71% (5 of 45 vs 14 of 47) in rate of CMV vertical transmission in women treated with 8 g/day valacyclovir following primary CMV infection in pregnancy. A phase 2, single-arm clinical trial, showed that 8 g/day valacyclovir administered to mothers of symptomatic infected foetuses increased the portion of asymptomatic neonates to 82% (34 of 41), compared with 43% (20 of 47) in untreated pregnancies from a historical cohort.. Studies in favour of using valacyclovir during pregnancy for prevention and treatment of congenital CMV infection are emerging but are still few. Randomized clinical trials on large cohorts of patients investigating the efficacy on prevention and treatment of congenital CMV are required. Unfortunately, this will be probably not be feasible at least in the short period. In the meantime, data on the 'off label' use of valacyclovir for CMV in pregnancy could be collected within a multicentre observational study.

Topics: Antiviral Agents; Cytomegalovirus Infections; Female; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Valacyclovir

Congenital Cytomegalovirus (CMV) infection remains a major cause of lifelong disability, with no systematic screening implemented in pregnancy or the postnatal period. In this review article, we outline the preventive strategies, antenatal prognostic features and experimental therapies as well as evidence of efficacy from recent trials.. A recent randomized, double blinded, placebo-controlled study investigated the efficacy of Valaciclovir in women contracting primary CMV in the periconception period or first trimester. They concluded that Valaciclovir at a dose of 8 g/day is effective in reducing the rate of foetal CMV infection following early maternal primary infection. Administration of CMV hyperimmune globulin (HIG) was investigated in a recent randomized double-masked controlled trial. This study concluded that CMV HIG was ineffective at reducing the risk of congenital CMV among women with primary CMV in early pregnancy.. Congenital CMV infection remains a significant cause of disability. There is currently no vaccine available, with the best preventive strategy being patient education on transmission as well as hygiene measures to reduce risk of exposure. Experimental therapies have been investigated in recent years and there is evidence supporting the use of Valaciclovir. Data for the efficacy of CMV HIG remains inconsistent and administration is currently limited to clinical trial settings.

Topics: Antiviral Agents; Cytomegalovirus Infections; Female; Humans; Immunoglobulins, Intravenous; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Ultrasonography, Prenatal; Valacyclovir

Over the past 25 years, several randomized controlled trials have investigated the efficacy of different antiviral agents for cytomegalovirus (CMV) prophylaxis in allogeneic hematopoietic cell transplantation. We performed a systematic literature review, conventional meta-analysis, and network meta-analysis using a random-effects model and risk ratios (RRs) with corresponding 95% confidence intervals (CIs) as effect estimates. Fifteen randomized controlled trials were identified, including 7 different antiviral agents: acyclovir, ganciclovir, maribavir, brincidofovir, letermovir, valacyclovir, and vaccine. Twelve trials used placebo as comparator while 3 trials compared different antiviral agents. We found evidence for CMV disease and infection being significantly reduced by antiviral prophylaxis, with an RR of .66 (95% CI, .48 to .90) and .63 (95% CI, .50 to .79). Across the network, ganciclovir showed the best relative efficacy for CMV disease while letermovir provided first rank of being the best option for CMV infection. The risk for death was not significantly influenced by antiviral prophylaxis in the meta-analysis, with an RR of .92 (95% CI, .78 to 1.08), as well as in the network meta-analysis. In terms of safety, letermovir was at least similar in comparison with placebo and most agents while both letermovir and acyclovir showed significantly reduced risk for serious adverse events compared with ganciclovir, with RRs of .55 (95% CI, .30 to 1.00) for letermovir and .63 (95% CI, .42 to .93) for acyclovir. With a probability of 81%, letermovir appears to be the best option in terms of safety. Future randomized head-to-head comparisons are needed to evaluate the definite efficacy and safety of different prophylactic strategies.

Topics: Acetates; Acyclovir; Allografts; Antiviral Agents; Benzimidazoles; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Male; Quinazolines; Ribonucleosides; Risk Factors; Valacyclovir

To define a clinically tailored therapeutic strategy for the treatment of viral anterior uveitis (VAU).. A PubMed search spanning the past 5 years was conducted using the MesH-terms "viral anterior uveitis" and "therapy.". The herpes simplex virus (HSV), the varicella zoster virus (VZV), and the cytomegalovirus (CMV) are the predominant pathogens in VAU. Other viruses, including rubella, chikungunya, and zika, have been linked with distinct forms of the disease. Depending on the causative agent and the host immunocompetence, the mainstay treatment for suspected VAU is a combination of topical or systemic antivirals and topical corticosteroids, supplemented with cycloplegics and intraocular-pressure-lowering medication.. Oral acyclovir, valacyclovir, and famciclovir are the mainstay of treatment for HSV- and VZV-induced infections. Brivudin serves as an alternative in insufficiently responsive cases. CMV-induced infections respond well to valganciclovir. A 3- to 12-month course of prophylactic treatment against recurrences is worth considering.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chikungunya Fever; Cytomegalovirus Infections; Eye Infections, Viral; Famciclovir; Herpes Simplex; Herpes Zoster Ophthalmicus; Humans; Rubella; Uveitis, Anterior; Valacyclovir; Zika Virus Infection

Until recently, management options in congenital cytomegalovirus (cCMV) infection have been either conservative or termination of pregnancy. However, medical therapies aimed at reducing the risk of infection and/or its severity have recently been investigated.. In a phase 2 open label, nonrandomized trial, valaciclovir (ValACV) was given to women carrying a CMV-infected fetus. ValACV was associated with a greater proportion of asymptomatic neonates when compared with a historical cohort (82 vs. 43%). However, the study design and the small number of treated women limit its applicability. Even though initial observational data suggested that hyperimmune globulin (HIG) therapy in pregnancy was associated with a significantly lower risk of cCMV, its efficacy has not been borne out in a subsequent phase 2 randomized, placebo controlled, double-blind study [cCMV 30% in the HIG group, 44% in the placebo group (P = 0.13)]. Furthermore, 11% of fetuses in the HIG group had transient or permanent abnormalities, compared with 16% in the placebo group.. ValACV might have a promising role in the antenatal treatment of cCMV infection, but definitive recommendations require further research. The use of HIG should currently be limited to the research setting.Video abstract http://links.lww.com/COID/A18.

Topics: Acyclovir; Antiviral Agents; Clinical Trials, Phase II as Topic; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Female; Fetal Diseases; Humans; Immunoglobulins; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic; Valacyclovir; Valine

Cytomegalovirus (CMV) congenital infection affects 0.7% of live births worldwide and is the leading cause of congenital neurological handicap of infectious origin. However, systematic screening for this infection has not been implemented in pregnancy or at birth in any country. This apparent paradox had been justified by persisting gaps in the knowledge of this congenital infection: uncertain epidemiological data, difficulty in the diagnosis of maternal infection, absence of validated prenatal prognostic markers, unavailability of an efficient vaccine and scarcity of data available on the treatment. However, in the last decade, new data have emerged towards better management of this congenital infection, including solid epidemiological data, good evidence for the accuracy of diagnosis of maternal CMV infection and good evidence for the feasibility of predicting the outcome of fetal infection by a combination of fetal imaging and fetal laboratory parameters. There is also some evidence that valaciclovir treatment of mothers carrying an infected fetus is feasible, safe and might be effective. This review provides an update on the evidence for diagnosis, prognosis and treatment of congenital infection in the antenatal period. These suggest a benefit to a proactive approach for prenatal congenital infections.

Topics: Acyclovir; Amniotic Fluid; Antibodies, Viral; Antiviral Agents; Ascites; Cytomegalovirus Infections; DNA, Viral; Female; Fetal Diseases; Humans; Hydrocephalus; Hydrops Fetalis; Immunization, Passive; Immunoglobulin G; Immunoglobulin M; Infectious Disease Transmission, Vertical; Lissencephaly; Microcephaly; Oligohydramnios; Polyhydramnios; Porencephaly; Pregnancy; Pregnancy Complications, Infectious; Seroconversion; Ultrasonography, Prenatal; Valacyclovir; Valine

Prevention of cytomegalovirus infection using antiviral prophylaxis or the pre-emptive therapy approach is an integral part of management of patients after solid organ transplantation. Regarding renal transplantation, valacyclovir is currently the only antiviral agent recommended for prophylaxis as an alternative to valganciclovir. This review article discusses studies documenting the efficacy and safety of valacyclovir prophylaxis as well as those comparing valacyclovir with other prophylactic regimens or with pre-emptive therapy. Also addressed are the economic aspects supporting the cost-effectiveness of valacyclovir prophylaxis and demonstrating lower costs compared with other cytomegalovirus preventive strategies.

Topics: Acyclovir; Antiviral Agents; Cost Savings; Cost-Benefit Analysis; Cytomegalovirus Infections; Drug Costs; Humans; Organ Transplantation; Treatment Outcome; Valacyclovir; Valine

The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis with the aim of preventing the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008.. To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause mortality in solid organ transplant recipients.. We searched MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials (CENTRAL) in The Cochrane Library to February 2004 for the first version of this review. The Cochrane Renal Group's specialised register was searched to February 2007 and to July 2011 for the first and current updates of the review without language restriction.. We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications and comparing different regimens of the same antiviral medications in recipients of any solid organ transplant. Studies examining pre-emptive therapy were excluded.. Two authors independently assessed study eligibility, risk of bias and extracted data. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes and by mean difference (MD) with 95% CI for continuous outcomes. Statistical analyses were performed using the random-effects model. Subgroup analysis and univariate meta-regression were performed using restricted maximum-likelihood to estimate the between study variance. Multivariate meta-regression was performed to investigate whether the results were altered after allowing for differences in drugs used, organ transplanted, and recipient CMV serostatus at the time of transplantation.. We identified 37 studies (4342 participants). Risk of bias attributes were poorly performed or reported with low risk of bias reported for sequence generation, allocation concealment, blinding and selective outcome reporting in 25% or fewer studies.Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 studies; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 studies; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 studies; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality from CMV disease (7 studies; RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduced the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but not fungal infection, acute rejection or graft loss.Meta-regression showed no significant difference in the relative benefit of treatment (risk of CMV disease or all-cause mortality) by organ transplanted or CMV serostatus; no conclusions were possible for CMV negative recipients of negative organs.Neurological dysfunction was more common with ganciclovir and valaciclovir compared with placebo/no treatment. In direct comparison studies, ganciclovir was more effective than aciclovir in preventing CMV disease (7 studies; RR 0.37, 95% CI 0.23 to 0.60) and leucopenia was more common with aciclovir. Valganciclovir and IV ganciclovir were as effective as oral ganciclovir. The efficacy and adverse effects of valganciclovir/ganciclovir did not differ from valaciclovir in three small studies. Extended duration prophylaxis significantly reduced the risk of CMV disease compared with three months therapy (2 studies; RR 0.20, 95% CI 0.12 to 0.35). Leucopenia was more common with extended duration prophylaxis but severe treatment associated adverse effects did not differ between extended and three month durations of treatment.. Prophylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients. These data suggest that antiviral prophylaxis should be used routinely in CMV positive recipients and in CMV negative recipients of CMV positive organ transplants.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Organ Transplantation; Randomized Controlled Trials as Topic; Valacyclovir; Valine

Systematic screening for cytomegalovirus (CMV) maternal infection is not recommended in most countries. Nevertheless, primary CMV infection will occur in around 1% of women. The vertical transmission rate is estimated to be around 30-50%. Newborns with congenital CMV infection remain asymptomatic in the majority of cases and around 10% will present with a wide range of abnormalities. Fetal infection can be diagnosed by amniocentesis with amplification of the viral genome in the amniotic fluid by polymerase chain reaction. This prenatal diagnosis is mainly performed when ultrasound abnormalities are observed. The purpose of this mini-review is to describe the management options when a fetus is known to be infected.

Topics: Acyclovir; Amniocentesis; Amniotic Fluid; Antiviral Agents; Congenital Abnormalities; Cytomegalovirus; Cytomegalovirus Infections; Decision Trees; Female; Fetal Diseases; Humans; Infant, Newborn; Male; Pregnancy; Prognosis; Severity of Illness Index; Ultrasonography; Valacyclovir; Valine

Prevention of cytomegalovirus (CMV) infection is an important part of clinical care provided to patients after solid organ transplantation. While the optimal preventive strategy has not been defined, most centers rely on universal prophylaxis or pre-emptive therapy. This article comments on recent studies designed to identify strategies that effectively reduce the incidence of late-onset CMV disease as the main problem associated with prophylaxis, and on recent data regarding the development of CMV-specific immunity depending on the CMV-preventive regimen used. Despite an apparent trend to prefer prophylaxis in clinical practice, this approach does not seem to be based on robust evidence.

Topics: Acyclovir; Antiviral Agents; Clinical Protocols; Cytomegalovirus Infections; Ganciclovir; Humans; Immunosuppressive Agents; Opportunistic Infections; Organ Transplantation; Randomized Controlled Trials as Topic; Valacyclovir; Valganciclovir; Valine

Viral skin infections are common findings in organ transplant recipients. The most important etiological agents are the group of human herpesviruses (HHV), human papillomaviruses (HPV), and molluscum contagiosum virus. HHV that are important in this group of patients are herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), HHV-6 and -7, and HHV-8, which causes Kaposi sarcoma (KS). HSV infections are characterized by their ability to establish latency and then reactivate at a later date. The most common manifestations of HSV infection in organ transplant recipients are mucocutaneous lesions of the oropharynx or genital regions. Treatment is usually with acyclovir, valaciclovir, or famciclovir. Acyclovir resistance may arise although the majority of acyclovir-resistant strains have been isolated from AIDS patients and not organ transplant recipients. In such cases, alternatives such as foscarnet, cidofovir, or trifluridine may have to be considered. VZV causes chickenpox as well as herpes zoster. In organ transplant recipients, recurrent herpes zoster can occur. Acute chickenpox in organ transplant patients should be treated with intravenous acyclovir. CMV infection occurs in 20-60% of all transplant recipients. Cutaneous manifestations, which include nonspecific macular rashes, ulcers, purpuric eruptions, and vesiculobullous lesions, are seen in 10-20% of patients with systemic infection and signify a poor prognosis. The present gold standard for treatment is ganciclovir, but newer drugs such as valganciclovir appear promising. EBV is responsible for some cases of post-transplant lymphoproliferative disorder, which represents the greatest risk of serious EBV disease in transplant recipients. HHV-6 and HHV-7 are two relatively newly discovered viruses and, at present, the body of information concerning these two agents is still fairly limited. KS is caused by HHV-8, which is the most recently discovered lymphotrophic HHV. Iatrogenic KS is seen in solid-organ transplant recipients, with a prevalence of 0.5-5% depending on the patient's country of origin. HPV is ubiquitous, and organ transplant recipients may never totally clear HPV infections, which are the most frequently recurring infections in renal transplant recipients. HPV infection in transplant recipients is important because of its link to the development of certain skin cancers, in particular, squamous cell carcinoma. Regular surve

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Cidofovir; Cytomegalovirus Infections; Cytosine; Drug Administration Schedule; Epstein-Barr Virus Infections; Famciclovir; Foscarnet; Herpes Zoster; Herpesviridae Infections; Humans; Immunocompromised Host; Molluscum Contagiosum; Organ Transplantation; Organophosphonates; Papillomavirus Infections; Skin Diseases, Viral; Trifluridine; Valacyclovir; Valine

The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis with the aim of preventing the clinical syndrome associated with CMV infection.. To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause mortality in solid organ transplant recipients.. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction.. Randomised and quasi-randomised controlled trials comparing antiviral medications with placebo or no treatment, trials comparing different antiviral medications and trials comparing different regimens of the same antiviral medications in recipients of any solid organ transplant.. Two reviewers independently assessed trial quality and extracted data from each trial. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). Subgroup analysis and univariate meta-regression were performed using restricted maximum-likelihood to estimate the between study variance. Multivariate meta-regression was performed to investigate whether the results were altered after allowing for differences in drugs used, organ transplanted and recipient CMV serostatus at the time of transplantation.. Thirty two trials (3737 participants) were identified. Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 trials; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 trials; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 trials; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality from CMV disease (seven trials; RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduced the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but not fungal infection, acute rejection or graft loss. Meta-regression showed no significant difference in the risk of CMV disease or all-cause mortality by organ transplanted or CMV serostatus; no conclusions were possible for CMV negative recipients of negative organs. In direct comparison trials, ganciclovir was more effective than aciclovir in preventing CMV disease (seven trials; RR 0.37, 95% Cl 0.23 to 0.60). Valganciclovir and intravenous ganciclovir were as effective as oral ganciclovir.. Prophylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients. They should be used routinely in CMV positive recipients and in CMV negative recipients of CMV positive organ transplants.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Organ Transplantation; Valacyclovir; Valine

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Herpes Zoster; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

The current arsenal of antiviral agents available to the practitioner is expanding rapidly, such that by the time this article goes to press, new drugs may have already been added. Although the majority of approved drugs have been developed for use in only a few viral infections (eg, HIV, herpesviruses, and papillomavirus), discoveries made in the development of these drugs may lead to antiviral agents effective against other viruses. In addition, new uses for the currently available drugs are under evaluation. This review of antiviral agents discusses the treatments available for viral infections such as herpes simplex virus, varicella zoster virus, cytomegalovirus, human papillomavirus, chronic viral hepatitis, and others.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Chickenpox; Cytomegalovirus Infections; Famciclovir; Foscarnet; Guanine; Hepatitis B; Hepatitis C; Herpes Genitalis; Herpes Simplex; Herpesvirus 3, Human; Herpesvirus 8, Human; Humans; Papillomavirus Infections; Sarcoma, Kaposi; Skin Diseases, Viral; Valacyclovir; Valine

Cytomegalovirus (CMV) has major consequences after allogeneic stem cell and solid organ transplantation. CMV may cause significant morbidity and mortality, and monitoring to detect reactivation to reduce disease or management of end organ disease is associated with increased resource utilization. Two other members of the beta-herpesvirus family, human herpesvirus (HHV) type 6 and HHV-7, are increasingly recognized as important pathogens in transplant recipients, either by direct infection (e.g., encephalitis, hepatitis, or pneumonitis) or via interaction with CMV. In addition to direct effects of CMV infection, such indirect effects as an increased risk for bacterial and fungal infections or impaired graft acceptance and function are important research topics. Diagnosis and treatment of CMV infection is currently more advanced than for HHV-6 and HHV-7.

Topics: Acyclovir; Antiviral Agents; Betaherpesvirinae; Clinical Trials as Topic; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Herpesviridae Infections; Herpesvirus 6, Human; Herpesvirus 7, Human; Humans; Organ Transplantation; Postoperative Complications; Treatment Outcome; Valacyclovir; Valine

Cytomegalovirus (CMV) infection and disease, with its extensive direct and indirect consequences, adds considerably to the cost of patient management in both solid organ and bone marrow transplantation. Antiviral prophylaxis for CMV infection can offer cost advantages over preemptive therapy and "wait-and-treat" approaches. Valacyclovir has demonstrated efficacy for CMV prophylaxis in renal, heart, and bone marrow transplantation and is cost-effective when compared with placebo in renal transplant recipients at high risk of CMV infection. In reducing CMV infection and disease, valacyclovir prophylaxis appears to be associated with reductions in indirect effects of CMV (acute graft rejection, other opportunistic infections) and, if these effects are considered, the potential exists for even greater savings to be made with valacyclovir therapy. Benefits of valacyclovir in transplantation extend beyond CMV to other herpesviruses and may be increased in some clinical situations by prolonging prophylaxis beyond 3 months.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Bone Marrow Transplantation; Cost-Benefit Analysis; Cytomegalovirus Infections; Graft Rejection; Health Care Costs; Heart Transplantation; Humans; Kidney Transplantation; Opportunistic Infections; Postoperative Complications; Prodrugs; Time Factors; Valacyclovir; Valine

A meta-analysis of 12 randomized trials (1574 patients) examined herpesvirus and related outcomes following organ transplantation over a range of acyclovir exposures (including valacyclovir). Overall, cytomegalovirus (CMV) infection (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.34-0.57; P<.001), CMV disease (OR, 0.41; 95% CI, 0.31-0.54; P<.001), death (OR, 0.60; 95% CI, 0.40-0.90; P=.01), opportunistic infection (OR, 0.70; 95% CI, 0.53-0.91; P=.009), acute graft rejection (OR, 0.67; 95% CI, 0.52-0.86; P<.001), herpes simplex virus disease (OR, 0.17; 95% CI, 0.12-0.24; P<.001), and varicella-zoster virus disease (OR, 0.06; 95% CI, 0.01-0.25; P<.001) were significantly reduced. Increased acyclovir exposure influenced more end points: Maximum efficacy resulted from valacyclovir (8 g/day). Increasing acyclovir exposure to that achieved with valacyclovir extends benefits of prophylaxis to include impact on graft rejection and opportunistic infections.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Graft Rejection; Herpes Simplex; Humans; Odds Ratio; Opportunistic Infections; Organ Transplantation; Postoperative Complications; Prodrugs; Randomized Controlled Trials as Topic; Treatment Outcome; Valacyclovir; Valine

Human cytomegalovirus (HCMV) infects about 60% of adults in developed world and more than 90% of developing countries population. In the immunocompetent host, initial infection and reactivation of latent infection are usually asymptomatic. However, in hosts with impaired cellular immune functions, such as transplant recipients, patients infected with human immunodeficiency virus (HIV) or undergoing anticancer chemo- and/or radiotherapy, the full pathogenic potential of the virus may be realized. HCMV is also among the most common causes of viral intrauterine infection affecting from 0.4 to 2.3% of live-born infants. Though in pregnant, immunocompetent women infections with HCMV are usually asymptomatic, severe infections may occur among congenitally infected fetuses and infants due to immaturity of their immune system. Approximately 40% of mothers with primary HCMV infections during gestation transmit virus to their infants. Although only 10% of infected infants are symptomatic at birth, 20 to 30% of these die. In addition, 5 to 15% of asymptomatic neonates are at risk of developing congenital anomalies later. In this outline we present anti-CMV drugs currently in clinical use and give examples of new molecules under laboratory and clinical development.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytomegalovirus Infections; Cytosine; Drugs, Investigational; Female; Foscarnet; Ganciclovir; Global Health; Humans; Infectious Disease Transmission, Vertical; Naphthalenesulfonates; Organophosphonates; Organophosphorus Compounds; Pregnancy; Pregnancy Complications, Infectious; Thionucleotides; Valacyclovir; Valganciclovir; Valine

Valaciclovir is an aciclovir prodrug used to treat infections caused by herpes simplex virus (HSV) and varicella zoster virus, and for prophylaxis against cytomegalovirus (CMV). Oral valaciclovir provides significantly better oral bioavailability than oral aciclovir itself, contributing to the need for less frequent administration. Several studies have demonstrated the efficacy of long term (> 90 days) therapy with valaciclovir for the suppression of genital HSV disease in otherwise healthy individuals with HSV infection. In 1 randomised, double-blind trial, once daily valaciclovir (1000 mg, 500 mg and 250 mg) produced statistically significant suppression of disease recurrence, as did twice daily valaciclovir 250 mg and aciclovir 400 mg. Valaciclovir dosages of > or = 500 mg daily are recommended for suppression of genital herpes recurrences in immunocompetent individuals. This disease occurs frequently in patients with human immunodeficiency virus (HIV) infection and, in a single randomised double-blind trial, prophylactic valaciclovir (1000 mg once daily or 500 mg twice daily) and aciclovir (400 mg twice daily) were found to be of similar efficacy in the suppression of genital herpes. However, a higher than expected dropout rate indicated that more studies of valaciclovir in patients with HIV are required. In a randomised trial of patients undergoing renal transplant, valaciclovir 2 g 4 times daily for 90 days significantly reduced the incidence and delayed the onset of CMV disease: the incidence in valaciclovir-treated patients who were CMV-seronegative at baseline, and recieived a kidney from a CMV-seropositive donor, was 3% versus 45% for placebo after 90 days of treatment. Acute graft rejection was also reduced in the valaciclovir-treated group. A small study in heart transplant patients compared valaciclovir (2 g 4 times daily) with aciclovir (200 mg 4 times daily) and found a significant reduction in CMV antigenaemia favouring valacilovir at the end of the treatment period. Additional reductions in other indices of CMV in those given valaciclovir compared with aciclovir were also noted. In a preliminary study of prophylaxis for CMV disease in bone marrow transplant recipients valaciclovir (2 g 4 times daily) was superior to aciclovir (800 mg 4 times daily) in terms of time to CMV viraemia or viruria. Although valaciclovir (8 g/day for approximately 30 weeks) reduced the incidence and time to CMV disease compared with aciclovir (3.2 g/day) in pati. Oral valaciclovir is an effective drug for the suppression of recurrent episodes of genital herpes in immunocompetent and immunocompromised individuals. (ABSTRACT TRUNCATED)

Topics: Acyclovir; Animals; Antiviral Agents; Cytomegalovirus Infections; Herpes Genitalis; Humans; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Postoperative Complications; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Herpes Genitalis; Herpes Zoster; Humans; Prodrugs; Valacyclovir; Valine

Viral lesions of the mouth in patients with HIV infection are common and these diseases any be a marker for HIV and disease progression. We review the spectrum of oral viral manifestations and discuss treatment modalities. The most common Epstein-Barr virus (EBV)-induced disorder in HIV-infected patients is oral hairy leukoplakia. EBV-related oral B-cell and T-cell lymphoma in AIDS patients has been described repeatedly. Herpes virus type 1 and rarely type 2 may lead to painful and resistant oral ulcers, and systemic treatment with acyclovir, valaciclovir or famciclovir is indicated. In acyclovir-resistant cases foscarnet is the treatment of choice. In recent years it has been documented that Kaposi's sarcoma, which often affects oral mucosa, is probably induced by herpesvirus type 8. Cytomegalovirus was found in 53% of cases with herpesviridae-induced mucosal ulcers as the only ulcerogenic viral agent in AIDS patients. In severe cytomegalovirus infection treatment with ganciclovir is helpful. Viral warts induced by different HPV may occur in the mouth. Several physical treatment modalities are possible in the oral mucosa. In AIDS patients mollusca contagiosa may occur as large and atypical lesions in the face and lips and rarely in the oral cavity. Cryotherapy is a bloodless treatment in such patients.

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Cytomegalovirus Infections; Disease Progression; Famciclovir; Foscarnet; Ganciclovir; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Leukoplakia, Hairy; Lymphoma, B-Cell; Lymphoma, T-Cell; Molluscum Contagiosum; Mouth Diseases; Mouth Neoplasms; Oral Ulcer; Prodrugs; Sarcoma, Kaposi; Stomatitis, Herpetic; Tumor Virus Infections; Valacyclovir; Valine; Virus Diseases; Warts

More than 90% of patients with HIV have been infected at some time with cytomegalovirus (CMV) and up to 40% of those with advanced HIV will develop CMV disease. The incidence of CMV disease is increasing but the prognosis for the patient remains poor.. It is therefore important to monitor patients with low CD4+ counts in order to identify those most at risk of developing CMV disease and to treat them before the disease becomes established. Polymerase chain reaction (PCR) is probably the most effective and sensitive method of detecting CMV and a positive result is predictive for development of CMV disease; more than 80% of patients with CMV retinitis are CMV PCR-positive at the time of diagnosis. PCR can also detect the presence of CMV up to 14 months before the development of retinitis.. In patients with detectable CMV, but no evidence of active infection, pre-emptive treatment with ganciclovir or valaciclovir has been shown to reduce the risk of developing retinitis in these high-risk patients. Such oral therapy, which is generally better tolerated than intravenous therapy and results in a better quality of life for the patient, is likely to be more effective at this stage whilst viral loads are low.. CMV PCR can be used to prospectively monitor patients in order to identify those most at risk of developing CMV retinitis. If CMV infection is diagnosed early, while viral loads are still low, pre-emptive oral therapy can be instituted which will reduce the chances of developing retinitis in those patients most at risk.

Topics: Acyclovir; Administration, Oral; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Ganciclovir; Humans; Polymerase Chain Reaction; Risk Factors; Valacyclovir; Valine

Over the past 15 years, acyclovir has become established as standard therapy for the management of herpes simplex virus infections, but there are areas where improvements might be made. Acyclovir has a relatively low oral bioavailability. As a result, valaciclovir, the L-valine ester of acyclovir, is being developed. This new drug produces enhanced plasma levels of acyclovir following oral dosing, which will not only allow more convenient dosing for the treatment of herpes simplex virus and varicella zoster virus (VZV) infections, but also mean that valaciclovir has the potential for superior clinical efficacy over acyclovir. This may broaden the potential utility of the drug to include human cytomegalovirus prophylaxis. Other new drugs in the antiherpes area include penciclovir and its pro-drug famciclovir, which have antiviral characteristics similar to acyclovir but no clinical benefit over and above that seen with acyclovir has been demonstrated. The synthesis of new specific antiherpes compounds has led to the discovery of a novel nucleoside analogue, 882C87, which has significantly greater activity against VZV than acyclovir. The compound also has a longer plasma half-life than acyclovir which may permit less frequent dosing.

Topics: Acyclovir; Arabinofuranosyluracil; Cytomegalovirus Infections; Ganciclovir; Guanine; Herpes Simplex; Herpesvirus 3, Human; Humans; Valacyclovir; Valine

Valacyclovir is currently the only pharmacological intervention demonstrated to reduce the risk of vertical CMV congenital infection within a randomized clinical trial in case of primary infection during pregnancy. So far, no data are available on the prognosis of children with congenital CMV infection diagnosed at birth after a negative amniocentesis whose mother were treated with valacyclovir during pregnancy, therefore it is essential to carry out a rigorous neurocognitive follow-up in these children in order to investigate the potential clinical consequence.

Topics: Amniocentesis; Child; Cytomegalovirus Infections; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Mothers; Pregnancy; Pregnancy Complications, Infectious; Valacyclovir

Cytomegalovirus is a common congenital infection, with high morbidity after an early primary maternal infection. No effective means exist to prevent viral transmission to the fetus. We aimed to investigate whether valaciclovir can prevent vertical transmission of cytomegalovirus to the fetus in pregnant women with a primary infection acquired early in pregnancy.. This prospective, randomised, double-blind, placebo-controlled trial was done at the Infectious Feto-Maternal Clinic of Rabin Medical Center (Petach Tikvah, Israel). Pregnant women aged 18 years or older, with serological evidence of a primary cytomegalovirus infection acquired either periconceptionally or during the first trimester of pregnancy, were randomly assigned to oral valaciclovir (8 g per day, twice daily) or placebo from enrolment until amniocentesis at 21 or 22 gestational weeks. Randomisation was done separately for participants infected periconceptionally or during the first trimester and was done in blocks of four. Patients and researchers were masked to participant allocation throughout the entire study period. The primary endpoint was the rate of vertical transmission of cytomegalovirus. Statistical analyses were done according to per-protocol principles. The study was registered at ClinicalTrials.gov, NCT02351102.. Between Nov 15, 2015, and Oct 8, 2018, we enrolled and randomly assigned 100 patients to receive valaciclovir or placebo. Ten patients were excluded, five from each study group; therefore, the final analysis included 45 patients (all singletons) in the valaciclovir group and 45 patients (43 singletons and two sets of twins) in the placebo group. In the valaciclovir group, including both first trimester and periconceptional infections, five (11%) of 45 amniocenteses were positive for cytomegalovirus, compared with 14 (30%) of 47 amniocenteses in the placebo group (p=0·027; odds ratio 0·29, 95% CI 0·09-0·90 for vertical cytomegalovirus transmission). Among participants with a primary cytomegalovirus infection during the first trimester, a positive amniocentesis for cytomegalovirus was significantly less likely in the valaciclovir group (two [11%] of 19 amniocenteses) compared with the placebo group (11 [48%] of 23 amniocenteses; p=0·020. No clinically significant adverse events were reported.. Valaciclovir is effective in reducing the rate of fetal cytomegalovirus infection after maternal primary infection acquired early in pregnancy. Early treatment of pregnant women with primary infection might prevent termination of pregnancies or delivery of infants with congenital cytomegalovirus.. None.

Topics: Adult; Antiviral Agents; Cytomegalovirus Infections; Double-Blind Method; Female; Humans; Infectious Disease Transmission, Vertical; Medication Adherence; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Time-to-Treatment; Valacyclovir

Cytomegalovirus (CMV) prophylaxis may prevent CMV indirect effects in renal transplant recipients. This study aimed to compare the efficacy of valganciclovir and valacyclovir prophylaxis for CMV after renal transplantation with the focus on chronic histologic damage within the graft.. From November 2007 through April 2012, adult renal transplant recipients were randomized, in an open-label, single-center study, at a 1:1 ratio to 3-month prophylaxis with valganciclovir (n = 60) or valacyclovir (n = 59). The primary endpoint was moderate-to-severe interstitial fibrosis and tubular atrophy assessed by protocol biopsy at 3 years evaluated by a single pathologist blinded to the study group. The analysis was conducted in an intention-to-treat population.. Among the 101 patients who had a protocol biopsy specimen available, the risk of moderate-to-severe interstitial fibrosis and tubular atrophy was significantly lower in those treated with valganciclovir (22% versus 34%; adjusted odds ratio, 0.31; 95% confidence interval, 0.11-0.90; P = 0.032 by multivariate logistic regression). The incidence of CMV disease (9% versus 2%; P = 0.115) and CMV DNAemia (36% versus 42%; P = 0.361) were not different at 3 years.. Valganciclovir prophylaxis, as compared with valacyclovir, was associated with a reduced risk of moderate-to-severe interstitial fibrosis and tubular atrophy in patients after renal transplantation.. Australian New Zealand Clinical Trials Registry ( ACTRN12610000016033 ). Registered on September 26, 2007.

Topics: Adult; Antibiotic Prophylaxis; Antiviral Agents; Australia; Cytomegalovirus; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Fibrosis; Graft Survival; Humans; Incidence; Intention to Treat Analysis; Kidney; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Transplantation, Homologous; Valacyclovir; Valganciclovir

Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness.. To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients.. A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014. The mean baseline Acute Physiology and Chronic Health Evaluation II score of all patients was 17.6.. Patients were randomized to receive anti-CMV prophylaxis with valacyclovir hydrochloride (n = 34) or low-dose valganciclovir hydrochloride (n = 46) for up to 28 days to suppress viral reactivation, or to a control group with no intervention (n = 44).. Time to first CMV reactivation in blood within the 28-day follow-up period following initiation of the study drug.. Among the 124 patients in the study (46 women and 78 men; mean [SD] age, 56.9 [16.9] years), viral reactivation in the blood occurred in 12 patients in the control group, compared with 1 patient in the valganciclovir group and 2 patients in the valacyclovir group (combined treatment groups vs control: hazard ratio, 0.14; 95% CI 0.04-0.50). Although this trial was not powered to assess clinical end points, the valacyclovir arm was halted prematurely because of higher mortality; 14 of 34 patients (41.2%) had died by 28 days, compared with 5 of 37 (13.5%) patients in the control arm at the point of the decision to halt this arm. Other safety end points showed similar outcomes between groups.. Antiviral prophylaxis with valacyclovir or low-dose valganciclovir suppresses CMV reactivation in patients with critical illness. However, given the higher mortality, a large-scale trial would be needed to determine the clinical efficacy and safety of CMV suppression.. clinicaltrials.gov Identifier: NCT01503918.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Critical Illness; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Opportunistic Infections; Respiration, Artificial; Valacyclovir; Valine; Virus Activation; Virus Inactivation

Congenital infection with human cytomegalovirus is a major cause of morbidity and mortality. A randomized controlled trial showed that high-dosage valacyclovir prevents cytomegalovirus disease in transplant recipients. Fetuses showing ultrasound features of infection are at high risk of being symptomatic at or before birth. In a pilot study, oral administration of high-dosage valacyclovir to mothers significantly decreased viral load and produced therapeutic concentrations in the blood of infected fetuses. A randomized controlled trial comparing prenatal treatment with valacyclovir against placebo in infected fetuses failed to recruit because women declined randomization. Randomized controlled trials in fetal medicine have often proven unacceptable by women who decline termination of pregnancy and are not prepared to resign themselves to the odds of the natural history of the disease.. We evaluated the efficacy of oral valacyclovir, 8 g daily, for pregnant women carrying a symptomatic cytomegalovirus-infected fetus, targeting a high-risk group for developing both neurosensory and neurological impairment.. We designed a multicenter, open-label, phase II study with 1 arm, using one of Simon's optimal 2-stage designs. Symptomatic fetuses were defined by the presence of measurable extracerebral or mild cerebral ultrasound symptoms. They were treated in utero from prenatal diagnosis at a median of 25.9 weeks' gestation until delivery or termination of pregnancy. Fetuses with severe brain anomalies on ultrasound were not included as were cases completely asymptomatic at presentation, because treatment was unlikely to modify either outcome. The primary endpoint was the proportion of asymptomatic neonates born to treated mothers.. At the interim analysis, 8 of 11 women delivered an asymptomatic neonate (required: ≥7). In step 2, 32 additional cases were included for a total of 43; the final number of asymptomatic neonates was 34, more than the 31 required to indicate efficacy according to the Simon 2-stage design. They remained asymptomatic at 12 months. High-dosage valacyclovir given for a median of 89 days to pregnant women carrying a moderately infected fetus was efficient at giving birth to asymptomatic neonates. Fetal blood viral loads decreased and platelet counts increased, both significantly (P = .01 and P < .001, respectively), between treatment initiation and birth after treatment completion, regardless of duration of fetal infection. Compared with a historical cohort obtained by a metaanalysis of the literature, the use of valacyclovir (8 g daily) significantly increased the proportion of asymptomatic neonates from 43% without treatment to 82% with treatment. Although the pill burden was high (16 pills a day) adherence to treatment was >90%. Finally, valacyclovir at this high dosage was extremely well tolerated.. Our results indicate that high-dosage valacyclovir given in pregnancy is effective for improving the outcome of moderately symptomatic infected fetuses. Although this study is not a randomized controlled trial, this is the first study reporting the efficacy of an antiviral drug to treat cytomegalovirus-infected fetuses. Moreover, this first study will allow new trials to be conducted, using valacyclovir as a baseline safe and effective treatment in pregnancy, to be compared to the new emerging and more potent anticytomegalovirus drugs that have not currently been tested in pregnancy.

Topics: Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Female; Fetal Blood; Fetal Diseases; Fetal Therapies; Humans; Infant, Newborn; Platelet Count; Pregnancy; Pregnancy Complications, Infectious; Pregnancy, High-Risk; Ultrasonography, Prenatal; Valacyclovir; Valine; Viral Load

The ANCA-associated vasculitides (AAV) are systemic autoimmune inflammatory disorders characterised by necrotising inflammation affecting small to medium-sized blood vessels. Despite improvements in survival, infection and cardiovascular disease remain leading causes of morbidity and mortality. Considerable evidence suggests that CD4 + CD28null T-cell expansions, predominantly seen in Cytomegalovirus (CMV) seropositive individuals, are associated with systemic dysregulation of immune function leading to a heightened risk of infection and cardiovascular disease. In patients with AAV, CD4 + CD28null expansions are driven by CMV and are associated with an increased risk of infection and mortality. The aim of this study is to explore in detail the ways in which CMV modulates the immune system and to determine whether treatment with valaciclovir blocks subclinical CMV reactivation in CMV seropositive AAV patients and ameliorates the CMV-induced adverse effects on the immune system.. CANVAS is a single-centre prospective open-label randomised controlled proof-of-concept trial of 50 adult CMV seropositive patients with stable AAV. Participants will be randomly allocated to receive valaciclovir orally (2 g QDS or reduced according to renal function) or no additional treatment for 6 months with an additional 6-month follow-up period. The primary outcome is the proportion of patients with CMV reactivation, as assessed by measurable viral load on quantitative blood and urine CMV polymerase chain reaction. The secondary outcomes are safety, change in the proportion of CD4+ CMV-specific T-cell population (defined as CD4 + CD28null cells) and change in soluble markers of inflammation from baseline to 6 months. Further tertiary and exploratory outcomes include persistence of the effect of valaciclovir on the proportion of CD4 + CD28null cells at 6 months post completion of treatment, change in the immune phenotype of CD4+ T cells and change in blood pressure and arterial stiffness parameters from baseline to 6 months.. The results of this study will enable larger studies to be conducted to determine whether by controlling subclinical CMV reactivation, we can improve clinical endpoints such as infection and cardiovascular disease. The potential impact of this study is not limited to AAV, as CD4 + CD28null cells have been linked to adverse outcomes in other inflammatory conditions and in the context of an ageing immune system.. ClinicalTrials.gov Identifier NCT01633476 (registered 29 June 2012).

Topics: Acyclovir; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antiviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Clinical Protocols; Cytomegalovirus; Cytomegalovirus Infections; England; Host-Pathogen Interactions; Humans; Proof of Concept Study; Prospective Studies; Research Design; Time Factors; Treatment Outcome; Valacyclovir; Valine; Viral Load; Virus Activation

Both valganciclovir and high-dose valacyclovir are recommended for cytomegalovirus prophylaxis after renal transplantation. A head-to-head comparison of both regimens is lacking. The objective of the study was to compare valacyclovir prophylaxis with valganciclovir, which constituted the control group.. In a randomized, open-label, single-center trial, recipients of renal transplants (recipient or donor cytomegalovirus-seropositive) were randomly allocated (1:1) to 3-month prophylaxis with valacyclovir (2 g four times daily) or valganciclovir (900 mg daily). Enrollment occurred from November of 2007 to April of 2012. The primary end points were cytomegalovirus DNAemia and biopsy-proven acute rejection at 12 months. Analysis was by intention to treat.. In total, 119 patients were assigned to valacyclovir (n=59) or valganciclovir prophylaxis (n=60). Cytomegalovirus DNAemia developed in 24 (43%) of 59 patients in the valacyclovir group and 18 (31%) of 60 patients in the valganciclovir group (adjusted hazard ratio, 1.35; 95% confidence interval, 0.71 to 2.54; P=0.36). The incidence of cytomegalovirus disease was 2% with valacyclovir and 5% with valganciclovir prophylaxis (adjusted hazard ratio, 0.21; 95% confidence interval, 0.01 to 5.90; P=0.36). Significantly more patients with valacyclovir prophylaxis developed biopsy-proven acute rejection (18 of 59 [31%] versus 10 of 60 [17%]; adjusted hazard ratio, 2.49; 95% confidence interval, 1.09 to 5.65; P=0.03). The incidence of polyomavirus viremia was higher in the valganciclovir group (18% versus 36%; adjusted hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.96; P=0.04).. Valganciclovir shows no superior efficacy in cytomegalovirus DNAemia prevention compared with valacyclovir prophylaxis. However, the risk of biopsy-proven acute rejection is higher with valacyclovir.

Topics: Acute Disease; Acyclovir; Adult; Antiviral Agents; Biomarkers; Biopsy; Cytomegalovirus; Cytomegalovirus Infections; Czech Republic; DNA, Viral; Drug Administration Schedule; Female; Ganciclovir; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Intention to Treat Analysis; Kidney Transplantation; Male; Middle Aged; Time Factors; Treatment Outcome; Valacyclovir; Valganciclovir; Valine; Viral Load

Studies in HIV-1-infected infants and HIV-1-exposed, uninfected infants link early cytomegalovirus (CMV) acquisition with growth delay and cognitive impairment. We investigated maternal valacyclovir to delay infant acquisition of CMV.. Pregnant women with HIV-1, HSV-2 and CD4 count >250 cells/µl were randomized at 34 weeks gestation to 500 mg twice-daily valacyclovir or placebo for 12 months. Maternal CMV DNA was measured in plasma at 34 weeks gestation, in cervical secretions at 34 and 38 weeks gestation, and in breast milk at 7 postpartum timepoints; infant CMV DNA was measured in dried blood spots at 8 timepoints including birth.. Among 148 women, 141 infants were compared in intent-to-treat analyses. Maternal and infant characteristics were similar between study arms. Infant CMV acquisition did not differ between study arms, with 46/70 infants (66%) in placebo arm and 47/71 infants (66%) in the valacyclovir arm acquiring CMV; median time to CMV detection did not differ. CMV DNA was detected in 92% of 542 breast milk specimens with no difference in CMV level between study arms. Change in cervical shedding of CMV DNA between baseline and 38 weeks was 0.40-log greater in the placebo arm than the valacyclovir arm (p = 0.05).. In this cohort of HIV-1-seropositive mothers, two-thirds of infants acquired CMV by one year. Maternal valacyclovir had no effect on timing of infant CMV acquisition or breast milk CMV viral loads, although it modestly reduced cervical CMV shedding. Maternal prophylaxis to reduce infant CMV acquisition warrants further evaluation in trials with antiviral agents.. ClinicalTrials.gov NCT00530777.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; HIV Seropositivity; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Milk, Human; Pregnancy; Premedication; Treatment Outcome; Valacyclovir; Valine; Viral Load; Virus Shedding

The aim of this study was to determine the cost impact of four different strategies for prevention of cytomegalovirus (CMV) disease after renal transplantation.. 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.. 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).. Valacyclovir prophylaxis is less expensive strategy compared with any other regimen.

Topics: Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Economics, Pharmaceutical; Female; Ganciclovir; Graft Survival; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prospective Studies; Valacyclovir; Valine

Prevention of cytomegalovirus (CMV) is essential in organ transplantation. The two main strategies are pre-emptive therapy, in which one screens for and treats asymptomatic CMV viremia, and universal antiviral prophylaxis. We compared these strategies and examined long-term outcomes in a randomized, open-label, single-center trial. We randomly assigned 70 renal transplant recipients (CMV-seropositive recipient or donor) to 3-month prophylaxis with valacyclovir (n=34) or pre-emptive valganciclovir for significant CMV viremia detected at predefined assessments through month 12 (n=36). Among the 55 patients who had a protocol biopsy specimen available at 3 years to allow assessment of the primary outcome, 9 (38%) of 24 patients in the prophylaxis group and 6 (19%) of 31 patients in the pre-emptive therapy group had moderate to severe interstitial fibrosis and tubular atrophy (odds ratio, 2.50; 95% confidence interval, 0.74-8.43; P=0.22). The prophylaxis group had significantly higher intrarenal mRNA expression of genes involved in fibrogenesis. The occurrence of CMV disease was similar in both groups, but pre-emptive therapy improved 4-year graft survival (92% versus 74%; P=0.049) as a result of worse outcomes in patients with late-onset CMV viremia. In conclusion, compared with valacyclovir prophylaxis, pre-emptive valganciclovir therapy may lead to less severe interstitial fibrosis and tubular atrophy and to significantly better graft survival.

Topics: Acyclovir; Adult; Antiviral Agents; Atrophy; Biopsy; Cytomegalovirus; Cytomegalovirus Infections; Female; Fibrosis; Follow-Up Studies; Ganciclovir; Graft Survival; Humans; Kaplan-Meier Estimate; Kidney; Kidney Transplantation; Longitudinal Studies; Male; Middle Aged; Treatment Outcome; Valacyclovir; Valganciclovir; Valine

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

To investigate if adjunctive valacyclovir, an antiviral medication, reduces symptoms of persistent schizophrenia in individuals who are seropositive for cytomegalovirus (CMV).. N=47 CMV seropositive schizophrenia outpatients were randomly assigned to receive valacyclovir 1 g twice daily (n=24) or placebo (n=23) for 16 weeks after a 2-week placebo run-in. Symptoms were assessed biweekly.. There was no significant difference in the change of positive, negative, general, or total PANSS symptoms between the valacyclovir vs. the placebo group.. The study did not demonstrate benefit of adjunctive valacyclovir for schizophrenia individuals with persistent symptoms who are CMV seropositive.

Topics: Acyclovir; Adult; Antipsychotic Agents; Antiviral Agents; Baltimore; Comorbidity; Cytomegalovirus Infections; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Valacyclovir; Valine

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.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Czech Republic; Ganciclovir; Humans; Incidence; Kidney Transplantation; Middle Aged; Prospective Studies; Valacyclovir; Valganciclovir; Valine

Alemtuzumab (Campath-1H)-based conditioning regimens are effective in preventing GVHD, but are associated with very high rates of cytomegalovirus (CMV) infection, a major limitation to their use. We evaluated 85 patients receiving conditioning with fludarabine 30 mg/m2/day (day -7 to day -3), alemtuzumab 20 mg/day (day -7 to day -3), and melphalan 140 mg/m2 on day -2. The initial patients received post transplant CMV prophylaxis with high-dose acyclovir. A very high incidence of CMV viremia was observed as has been commonly reported after alemtuzumab-based conditioning. Sixty-seven subsequent patients received pre-transplant ganciclovir and high-dose valacyclovir after engraftment. The cumulative incidence of CMV infection in the valacyclovir cohort was 29%. This compared favorably to the cumulative incidence of 53% in patients receiving only acyclovir (P = 0.004) and to literature data. CMV prophylaxis with pre-transplant ganciclovir and high-dose valacyclovir after engraftment appears effective in preventing the excessive incidence of CMV infection after alemtuzumab-based conditioning regimens.

Topics: Acyclovir; Adolescent; Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Agents; Antiviral Agents; Bone Marrow Transplantation; Cytomegalovirus Infections; Female; Ganciclovir; Hematologic Neoplasms; Humans; Incidence; Male; Middle Aged; Transplantation Conditioning; Transplantation, Homologous; Valacyclovir; Valine

Cytomegalovirus (CMV) disease is a risk factor for allograft rejection in renal transplant (RTx) recipients. However, the role of asymptomatic CMV infection remains controversial.. To determine the impact of CMV disease and asymptomatic infection on biopsy-proven acute rejection (BPAR) during 12 months post-RTx.. A total of 106 consecutive RTx recipients at risk for CMV (donor and/or recipient CMV seropositive) were followed prospectively for 12 months post-RTx. CMV activity was monitored using nested PCR from whole blood. Three-month prophylaxis with valacyclovir or ganciclovir was given to 94 patients. BPAR episodes were classified according to the Banff 97 criteria. Multivariate Cox proportional hazards model was used to estimate the effect of CMV disease, asymptomatic infection, and other covariates on BPAR.. Asymptomatic CMV infection occurred in 23% of the patients and 10% developed CMV disease. The incidence of BPAR was 29%. CMV disease was an independent risk factor for BPAR (HR=3.0, P=0.014), while asymptomatic CMV infection was not (P=0.987). In addition to CMV disease, expanded criteria donor and donor age were independent predictors for BPAR. In univariate analysis, valacyclovir (HR=0.26, P=0.008) decreased the risk of BPAR. A similar trend was observed with ganciclovir (HR=0.42, P=0.058). Only valacyclovir remained significant in multivariate analysis (HR=0.18, P=0.044).. CMV disease, but not asymptomatic infection, is an independent risk factor for BPAR during the first 12 months post-RTx.

Topics: Acute Disease; Acyclovir; Antiviral Agents; Carrier State; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Humans; Incidence; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Postoperative Complications; Prospective Studies; Risk Factors; Treatment Outcome; Valacyclovir; Valine

In this prospective single-center study, we evaluated the efficacy and safety of valaciclovir (VACV) in the prevention of cytomegalovirus (CMV) infection after allogeneic bone marrow transplantation (BMT). The study population consisted of 12 patients who underwent allogeneic BMT from an unrelated donor. Patients received acyclovir (ACV) intravenously until they became able to take VACV orally. VACV was administered at a daily dose of 3000 mg and continued until day 100. CMV infection was monitored by CMV antigenemia assay and real-time polymerase chain reaction analysis of plasma. Thirty-five patients who did not receive any form of CMV chemoprophylaxis served as control subjects. CMV infection was detected in 4 (33.3%) of the 12 patients and in 24 (68.6%) of the 35 control subjects (P < .05). The onset of CMV infection was significantly delayed in the VACV group (median, day 43) compared with the control group (median, day 28.5; P < .01). Gastrointestinal symptoms as an adverse event due to VACV administration were observed in 2 patients. The plasma levels of ACV after VACV administration were measured in 8 patients and were similar to those in the healthy subjects. In conclusion, VACV shows normal absorption, even in the early posttransplantation period, and may prevent or delay CMV infection effectively and safely in allogeneic BMT recipients.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Bone Marrow Transplantation; Cytomegalovirus Infections; DNA, Viral; Female; Humans; Lymphoproliferative Disorders; Male; Middle Aged; Prospective Studies; Transplantation, Homologous; Valacyclovir; Valine

Both oral ganciclovir and valacyclovir decrease the incidence of cytomegalovirus (CMV) disease after renal transplantation. Moreover, valacyclovir has been shown to reduce the risk of acute rejection. Our study was designed to compare the efficacy and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease after renal transplantation.. A total of 83 patients were prospectively randomized to 3-month treatment with oral ganciclovir (3 g/day, n=36, GAN) or oral valacyclovir (8 g/day, n=35, VAL). A control group (DEF, n=12) was managed by deferred therapy.. No differences were found in demography, immunosuppression, or donor/recipient CMV serology. The 12-month incidence of CMV disease was 67% in the DEF group compared with 6% in the GAN group and 3% in the VAL group (P<0.001 GAN or VAL vs. DEF; P=0.575 GAN vs. VAL). The biopsy-confirmed acute rejection rate at 12 months was 12% in the VAL group compared with 34% in the GAN group (P=0.030) and 58% in the DEF group (P<0.001). The difference between the GAN and DEF groups was not significant (P=0.087). The average CMV-associated costs per patient were $3,072, $2,906, and $4,906 in the GAN, VAL, and DEF groups, respectively.. Valacyclovir and oral ganciclovir are equally effective in the prevention of CMV disease after renal transplantation. Both regimens are cost-effective. Valacyclovir is associated with a significantly reduced risk of acute rejection compared with both ganciclovir prophylaxis and deferred therapy.

Topics: Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Histocompatibility Testing; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Reoperation; Risk Factors; Survival Analysis; Time Factors; Transplantation, Homologous; Valacyclovir; Valine

To compare the efficacy, costs and safety of oral ganciclovir and valacyclovir in the prophylaxis of cytomegalovirus (CMV) disease in renal transplant (RTx) recipients at high risk of CMV disease.. A total of 83 patients were prospectively randomized to 3-month treatment with either oral ganciclovir (3 g/day) or oral valacyclovir (8 g/day). A 3rd group received no prophylaxis. Forty-nine patients were considered to be at high risk of CMV disease due to D+R- serologic status, OKT3/ATG treatment and/or acute rejection within 12 months after RTx. Twenty-three high-risk patients were treated with ganciclovir (GAN group), 17 patients with valacyclovir (VAL group), and 9 patients received no prophylaxis (C group).. No significant differences were found among the groups in their demographic characteristics, immunosuppressive protocols, D/R CMV serology, or CMV risk factors. The 12-month incidence of CMV disease was 89% in the C group compared with 9% in the GAN group and 6% in the VAL group (p < 0.001, GAN or VAL vs. C; p = 0.713, GAN vs. VAL). Treatment failure (death, graft loss, CMV disease or withdrawal from study) occurred in 17, 6, and 89% in the GAN, VAL, and C groups, respectively (p < 0.001, GAN or VAL vs. C; p = 0.285, GAN vs. VAL). The average CMV-associated costs per patient were EUR 3,161, 3,757, and 7,247 in the GAN, VAL, and C groups, respectively (p = 0.027).. Valacyclovir and oral ganciclovir are equally effective in the prophylaxis of CMV disease in high-risk RTx patients. Both regimens are cost-effective and help reduce CMV-associated costs by nearly 50% compared with patients without prophylaxis.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Graft Survival; Health Care Costs; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prospective Studies; Risk Factors; Valacyclovir; Valine; Viremia

An open, prospective, randomised study was conducted to compare the safety and efficacy of valacyclovir vs. oral ganciclovir for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. Eighty-three renal transplant recipients were assigned randomly to receive valacyclovir (n=43) or oral ganciclovir (n=40) for the first 3 months after transplantation. Both groups were similar in terms of demographics, primary renal disease, graft source, HLA matching, immunosuppressive therapy and donor-recipient CMV antibody status. CMV infection was diagnosed by detection of virus DNA in plasma with the Amplicor CMV Test. CMV disease was observed in only one patient belonging to the ganciclovir group, who developed enterocolitis 6 months post-transplantation. No difference was observed between the two treatment groups with respect to detection of CMV DNA, virus infections other than CMV, acute rejection episodes, and serum creatinine levels at 3 and 6 months following transplantation. An increased number of bacterial infections was noted in the ganciclovir group (p 0.003). No adverse reactions with either treatment were reported. The estimated cost of valacyclovir treatment was 20% higher than that of ganciclovir treatment. Overall, both valacyclovir and oral ganciclovir were found to be effective and safe for CMV prophylaxis in renal transplant recipients. Decisions regarding prophylactic regimens should include additional criteria, such as cost or possible development of resistance.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Costs and Cost Analysis; Cytomegalovirus Infections; Female; Ganciclovir; Greece; Humans; Kidney Transplantation; Male; Postoperative Complications; Valacyclovir; Valine

In this multicenter, randomized study, cytomegalovirus (CMV)-seropositive patients who received an allogeneic bone marrow transplant were provided high-dose intravenous acyclovir (500 mg/m(2) q8h) from the day of transplantation until engraftment. The patients were then randomly assigned to receive either oral valacyclovir, 2 g q.i.d. (n=83), or intravenous ganciclovir, 5 mg/kg q12h for 1 week, then 6 mg/kg once daily for 5 days per week (n=85), until day 100 after transplantation. CMV infection occurred in 12% of the patients who received valacyclovir and in 19% of the patients who received ganciclovir (hazard ratio [HR], 1.042; 95% confidence interval [CI], 0.391-2.778; P=.934). CMV disease developed in only 2 patients who received valacyclovir and in 1 patient who received ganciclovir (HR, 1.943; 95% CI, 0.176-21.44; P=.588). Oral valacyclovir can be an effective alternative to intravenous ganciclovir for prophylaxis of CMV disease after bone marrow transplantation.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Bacterial Infections; Bone Marrow Transplantation; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Injections, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Mycoses; Sepsis; Survival Analysis; Transplantation, Homologous; Valacyclovir; Valine

We tested whether health related quality of life (HRQOL) predicts mortality, development of active cytomegalovirus (CMV) disease, and study retention. We studied 957 patients with CD4 counts <100 cells/mm(3) in AIDS Clinical Trials Group Protocol 204, a randomized, double-blind trial comparing three prophylactic regimens against CMV end-organ disease. The MOS-HIV, a brief HRQOL questionnaire, generated physical health summary (PHS) and mental health summary (MHS) scores. We used Cox proportional hazards to predict events by baseline HRQOL, adjusted for treatment, demographics, and CD4. Each point increase in baseline PHS decreased the risk of death by 4%, CMV by 2%, and dropout by 2%. Each point increase in baseline MHS decreased the risk of death by 4% and study dropout by 1%. In conclusion, self-rated physical and mental health demonstrated predictive validity for survival, CMV end-organ disease, and retention in advanced HIV patients. The results show the clinical importance of HRQOL and may facilitate interpretation by clinicians.

Topics: Acute Disease; Acyclovir; Adult; Age Factors; Anti-HIV Agents; Cytomegalovirus Infections; Double-Blind Method; Health Status; HIV Infections; Humans; Middle Aged; Patient Dropouts; Predictive Value of Tests; Proportional Hazards Models; Psychiatric Status Rating Scales; Quality of Life; Racial Groups; Sex Factors; Survival Rate; Valacyclovir; Valine

The study was an investigation of the effect of the antiviral medication valacyclovir on the symptoms of outpatients with persistent schizophrenia.. Oral valacyclovir, 1 g twice daily, was administered to 65 outpatients over 16 weeks along with their usual psychiatric medications. Changes in psychiatric symptoms were measured with the Positive and Negative Syndrome Scale and were tested for correlations with antibodies to potentially neurotropic human herpesviruses, as measured by immunoassay before the start of the therapy.. There was a significant improvement in the psychiatric symptoms of individuals who were seropositive for cytomegalovirus. Improvement was not associated with antibodies to other herpesviruses or to a range of demographic and clinical variables.. The replication of cytomegalovirus may contribute to the symptoms of schizophrenia in some individuals.

Topics: Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prodrugs; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Valacyclovir; Valine

Oral ganciclovir and valacyclovir reduce the incidence of cytomegalovirus (CMV) disease after renal transplantation (RTx). Our study was designed to compare the efficacy, costs, and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease over the first 6 months after RTx. A total of 38 patients was randomized to 3-month treatment with either oral ganciclovir (1 g t.i.d., n=14, GAN group) or oral valacyclovir (2 g q.i.d., n=12, VAL group). A third group (C, n=12) received no prophylaxis. The patients were monitored by CMV-nested PCR in whole blood. No differences were found between the groups in their demographic characteristics, immunosuppressive protocols, or donor and recipient CMV serology. Thirty-six out of 38 (94.7%) recipients were CMV-seropositive. Over the 6-month post-RTx period, there were 13 episodes of CMV disease in eight (66.7%) patients of the C group compared with none in the GAN and VAL groups ( P=0.0005, GAN vs C; P=0.001, VAL vs C). The incidence of CMV viremia was 30.8%, 50.0%, and 91.7% in the GAN, VAL, and C groups, respectively ( P=0.004, GAN vs C; P=0.07, VAL vs C; P=NS, GAN vs VAL). Treatment failure (death, graft loss, CMV disease, or withdrawal from study) occurred in 14.3%, 0% and 66.7% in the GAN, VAL, and C groups, respectively ( P=0.014, GAN vs C; P=0.001, VAL vs C; P=NS, GAN vs VAL). The average CMV-associated costs per patient (in 2001 euros) were 2,449+/-1,178, 2,485+/-581, and 4,259+/-4,616 in the GAN, VAL, and C groups, respectively. Ganciclovir and valacyclovir were well tolerated, with ganciclovir having had to be withdrawn shortly in one patient only because of thrombocytopenia. In conclusion, oral ganciclovir and valacyclovir are equally safe and effective in the prophylaxis of CMV disease after RTx. Both are cost-effective and help reduce CMV-associated costs by some 40% compared with patients without prophylaxis.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Cadaver; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Ganciclovir; Humans; Kidney Diseases; Kidney Transplantation; Living Donors; Male; Middle Aged; Postoperative Complications; Prospective Studies; Renal Insufficiency; Tissue Donors; Valacyclovir; Valine

Cytomegalovirus (CMV) is a major cause of serious morbidity following solid organ transplantation via both direct and indirect mechanisms. The aim of this study was to investigate the efficacy and safety of valacyclovir prophylaxis in heart transplant recipients.. Twenty-seven CMV seropositive adults due to receive a heart transplant were included in a single-center, randomized, double-blind study. Patients were randomized to receive either oral valacyclovir 2000 mg or oral acyclovir 200 mg four times daily starting within 3 days of heart transplant and continuing for 90 days. The primary outcome measure was time to development of CMV antigenemia assessed for 6 months after surgery. Other measures were time to asymptomatic CMV infection, symptomatic CMV infections, and end-organ CMV disease. Patients were monitored for other herpes infections, other opportunistic infections, and acute graft rejection. Safety was assessed by evaluating changes in hematology and clinical chemistry parameters and by the occurrence of adverse events.. The median time to CMV antigenemia was 19 days for the acyclovir group compared with 119 days for the valacyclovir group (hazard ratio 0.42; 95% CI, 0.18-0.99; p = 0.049). Similar delays of approximately 100 days were found for CMV infection, symptomatic CMV infection, and CMV disease. There was also a trend for delayed acute rejection, and fewer opportunistic or other herpesvirus infections occurred in the valacyclovir group. Valacyclovir was well tolerated in the study population.. Oral valacyclovir is a safe and effective mode of prophylaxis of CMV after heart transplantation.

Topics: Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Double-Blind Method; Endpoint Determination; Female; Graft Rejection; Heart Transplantation; Humans; Incidence; Male; Middle Aged; Severity of Illness Index; Time Factors; Treatment Outcome; United Kingdom; Valacyclovir; Valine

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.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Bone Marrow Transplantation; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Female; Humans; Male; Middle Aged; Prodrugs; Survival Analysis; Therapeutic Equivalency; Transplantation, Homologous; Valacyclovir; Valine; Virus Activation

Cytomegalovirus (CMV) disease is a common complication of patients with advanced human immunodeficiency virus infection. The aim of the present study, based on a case-cohort design, was to determine the predictive value of follow-up and baseline qualitative plasma CMV polymerase chain reaction (PCR) values for CMV end-organ disease in 378 patients (158 who progressed to CMV end-organ disease and 220 who did not develop CMV disease). These patients are part of the full AIDS Clinical Trials Group 204 multinational study (1227 patients), a randomized, controlled trial that compared the effects of valacyclovir with those of acyclovir for CMV disease prevention. Baseline PCR positivity was a significant risk factor for CMV disease progression (relative risk [RR], 1.81; 95% confidence interval [CI], 1.09-3.00). In multivariate analyses, time-updated PCR positivity was strongly associated with progression to CMV end-organ disease (RR, 4.42; 95% CI, 2.87-6.81). Change in cumulative PCR status was informative for the risk of subsequent CMV disease.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Case-Control Studies; Cytomegalovirus; Cytomegalovirus Infections; HIV Infections; Humans; Male; Multivariate Analysis; Polymerase Chain Reaction; Predictive Value of Tests; Risk Factors; Valacyclovir; Valine

Cytomegalovirus (CMV) disease is a major cause of morbidity and mortality in solid organ transplant patients and is associated with large additional healthcare expenditures. An economic evaluation of valaciclovir CMV prophylaxis in a renal transplant population is reported.. Medical resource use data were collected alongside a multicenter multinational randomized, placebo-controlled, double-blind trial of valaciclovir CMV prophylaxis in renal transplantation. Patients were stratified into donor seropositive/recipient sero-negative (D+R-) and recipient seropositive (R+) groups. Patients were followed-up 6 months posttransplant. A cost-effectiveness analysis from the perspective of the French health care system was performed using the number of cases of CMV disease avoided at 6 months as the clinical endpoint.. Resource use was significantly increased among patients who developed CMV disease compared to those who did not develop disease. In the high risk D+R- group, valaciclovir prophylaxis was associated with an average of 5.5 fewer inpatient hospital days (P < OR =0.05) and with significantly lower use of other healthcare resources. In the R+ group, valaciclovir prophylaxis prevented cases of CMV disease at a marginally greater mean cost per patient compared with placebo. For D+R- patients valaciclovir prophylaxis was therefore an economically superior strategy, resulting in fewer cases of CMV disease and lower total mean healthcare expenditures.. Valaciclovir CMV prophylaxis in renal transplantation is a more cost-effective therapy compared with placebo, in the high-risk D+R- patient population. For the R+ group, the incremental cost per case of CMV disease was modest.

Topics: Acyclovir; Adolescent; Adult; Aged; Cost-Benefit Analysis; Cytomegalovirus Infections; Female; Humans; Kidney Transplantation; Male; Middle Aged; Valacyclovir; Valine

Cytomegalovirus (CMV) disease is a major complication of organ transplantation. We hypothesized that prophylactic treatment with valacyclovir would reduce the risk of CMV disease.. A total of 208 CMV-negative recipients of a kidney from a seropositive donor and 408 CMV-positive recipients were randomly assigned to receive either 2 g of valacyclovir or placebo orally four times daily for 90 days after transplantation, with the dose adjusted according to renal function. The primary end point was laboratory-confirmed CMV disease in the first six months after transplantation.. Treatment with valacyclovir reduced the incidence or delayed the onset of CMV disease in both the seronegative patients (P<0.001) and the seropositive patients (P=0.03). Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo recipients and 3 percent among valacyclovir recipients. Among the seropositive patients, the respective values were 6 percent and 0 percent. At six months, the incidence of CMV disease was 45 percent among seronegative recipients of placebo and 16 percent among seronegative recipients of valacyclovir; it was 6 percent among seropositive placebo recipients and 1 percent among seropositive valacyclovir recipients. At six months, the rate of biopsy-confirmed acute graft rejection in the seronegative group was 52 percent among placebo recipients and 26 percent among valacyclovir recipients (P=0.001). Treatment with valacyclovir also decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources. Hallucinations and confusion were more common with valacyclovir treatment, but these events were not severe or treatment-limiting. The rates of other adverse events were similar among the groups.. Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation.

Topics: Acyclovir; Adult; Antiviral Agents; Cadaver; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Female; Graft Rejection; Health Resources; Humans; Incidence; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prodrugs; Serologic Tests; Valacyclovir; Valine

Virus load is a major risk factor for disease in many human viral infections, especially human immunodeficiency virus (HIV) disease. The effect of cytomegalovirus (CMV) load on disease progression and the influence of antiviral chemotherapy on surrogate markers of replication was investigated in 310 patients with advanced HIV disease in a randomized controlled trial that compared the effects of valacyclovir with those of acyclovir. Sequential blood and urine samples were analyzed by polymerase chain reaction (PCR), for human CMV (HCMV) DNA. In multivariate analyses, elevated virus load in both blood and urine at baseline was associated with increased risk of HCMV disease (relative hazard, 1.49 and 1.44 per log increase, respectively). Elevated virus load in blood at baseline was also associated with a significantly shorter survival time (log rank, P=. 0001). In time-updated analyses, valacyclovir significantly suppressed the virus load in subjects who were PCR positive at baseline (in blood or urine), when compared with the combined acyclovir arms.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Analysis of Variance; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Disease-Free Survival; HIV Infections; Humans; Multivariate Analysis; Polymerase Chain Reaction; Prodrugs; Risk Factors; Survival Rate; Time Factors; Valacyclovir; Valine; Virus Replication

Cytomegalovirus (CMV) disease is a common complication of advanced human immunodeficiency virus (HIV) infection. Administration of oral valaciclovir, a valine ester of acyclovir, achieves sufficient plasma acyclovir levels to inhibit many clinical isolates. Acyclovir has been associated with enhanced survival in AIDS but not with CMV disease prevention. CMV-seropositive patients (1227) with CD4 cell counts <100/mm3 were enrolled in a randomized, double-blind trial. Valaciclovir, 8 g/day, was compared with acyclovir, 3.2 or 0.8 g/day, for CMV prevention; all three arms were compared for survival. The confirmed CMV disease rate was 11.7% among valaciclovir recipients and 17.5% in the pooled acyclovir arms, a 33% reduction in risk. Time to confirmed CMV disease was significantly longer for the valaciclovir group (P = .03). A trend toward earlier mortality for valaciclovir recipients was seen (P = .06). Toxicity and earlier medication discontinuation were more common in this group. Valaciclovir significantly reduces the risk of CMV disease. Further exploration of a better-tolerated dose is warranted.

Topics: Acyclovir; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Infections; Double-Blind Method; Female; Humans; Male; Valacyclovir; Valine

Samples of blood and urine were collected at baseline, week 4, and week 8 and then every 8 weeks from 310 patients entering a controlled trial of prophylaxis with valaciclovir versus acyclovir. Samples were tested under code by polymerase chain reaction (PCR) in one laboratory. The median number of samples collected from each patient was 5 for blood (range, 0-15) and 5 for urine (range, 0-15). Both baseline PCR viremia and PCR viruria were significantly associated with future cytomegalovirus (CMV) disease (P = .002 and P = .02, respectively). The greatest effect of valaciclovir on CMV disease was seen in patients who were PCR-positive in blood at baseline (P = .002), although a significant effect was also seen in those who were PCR-negative in urine (P = .02). Thus, PCR viremia provides prognostic information about CMV disease in AIDS patients, and valaciclovir showed activity as both a preemptive and prophylactic agent.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Double-Blind Method; Female; Humans; Male; Multivariate Analysis; Polymerase Chain Reaction; Prognosis; Valacyclovir; Valine; Viremia

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Double-Blind Method; Hemolytic-Uremic Syndrome; HIV Infections; Humans; Male; Middle Aged; Prodrugs; Prospective Studies; Purpura, Thrombotic Thrombocytopenic; Risk Factors; Valacyclovir; Valine

A study (ACTG 204) involving the effect of valacyclovir in preventing CMV disease in persons with advanced HIV infection (CD4 count under 100) was stopped because there were more deaths in the valacyclovir arm than in either (high dose/low dose) acyclovir arms of the study. There is no obvious explanation. It is believed the high doses of valacyclovir used were too high for this patient population; this may have led to side effects and resulting breaks in treatment that could have adversely affected survival. A greater survival effect may have been seen with acyclovir due to greater time on treatment, or greater consistency of treatment. However, two studies presented at the Human Retroviruses conference in Washington, D.C. failed to find a survival benefit of acyclovir. Further investigation into ACTG 204's design and findings are underway.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Ethics, Medical; Humans; Placebos; Survival Analysis; Valacyclovir; Valine

HIV-related treatment and prevention strategies for opportunistic infections presented at the 1995 International Conference on Antimicrobial Agents and Chemotherapy (ICAAC) are highlighted. Research highlights include valaciclovir for CMV prophylaxis, oral ganciclovir for preventing CMV, resistant CMV, and cidofovir (HPMPC) for CMV. Other topics discuss treatments of Mycobacterium avium complex, opportunistic infections and HIV viremia; and reports on the effects of influenza and pneumococcal immunizations on HIV viral load.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Bacterial Vaccines; CD4 Lymphocyte Count; Cidofovir; Clinical Trials as Topic; Cytomegalovirus Infections; Cytosine; Drug Resistance, Microbial; Ganciclovir; HIV; Humans; Influenza Vaccines; Mycobacterium avium-intracellulare Infection; Organophosphonates; Organophosphorus Compounds; Pneumonia; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; United States; Valacyclovir; Valine; Viremia

Questions are being raised about the efficacy of oral ganciclovir (Cytovene) in preventing cytomegalovirus (CMV), and the toxicity of valaciclovir, a derivative of acyclovir, when administered in high doses. Two government studies (Syntex 1654 and CPCRA 023) of oral ganciclovir have resulted in conflicting results. The studies are under investigation in an attempt to resolve the differences. CPCRA has led to concerns about Cytovene, including its potential for resistance and its relatively high cost. Another study shows two grams of valaciclovir, four times per day, produces the same blood levels as intravenous acyclovir. However, both are toxic levels and neither drug is viewed as particularly effective.

Topics: Acyclovir; Administration, Oral; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Ganciclovir; Humans; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome; Valacyclovir; Valine

Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost.. In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis.. Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%,. Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Humans; Retrospective Studies; Valacyclovir

Congenital cytomegalovirus (CMV) infection is the leading cause of non-genetic hearing and neurological deficits. The aim of our study was to evaluate the efficacy and safety of valacyclovir (VCV) treatment in preventing CMV transmission to the fetus after maternal primary infection.. This was a retrospective, multicenter study evaluating the rate of maternal-fetal CMV transmission in pregnancies with maternal primary CMV infection treated with VCV at a dosage of 8 g per day (VCV group) compared with a control group of untreated women. Each case underwent virological testing to confirm maternal primary infection and to provide accurate dating of onset of infection. The primary outcome was the presence of congenital CMV infection at birth diagnosed based on polymerase chain reaction analysis of saliva, urine and/or blood samples. The efficacy of VCV treatment was assessed using logistic regression analysis adjusted for a propensity score.. In total, 143 patients were included in the final analysis, of whom 59 were in the VCV group and 84 were in the untreated control group. On propensity-score-adjusted analysis, VCV treatment was significantly associated with an overall reduction in the rate of maternal-fetal CMV transmission (odds ratio, 0.40 (95% CI, 0.18-0.90); P = 0.029). The rate of maternal-fetal CMV transmission, determined at birth, in the VCV vs control group was 7% (1/14) vs 10% (1/10) after periconceptional maternal primary infection (P = 1.00), 22% (8/36) vs 41% (19/46) after first-trimester maternal primary infection (P = 0.068) and 25% (2/8) vs 52% (14/27) after second-trimester maternal primary infection (P = 0.244). When analyzing the efficacy of VCV treatment according to maternal viremia at treatment initiation, there was a trend towards greater efficacy when patients were viremia-positive (21% vs 43%; P = 0.072) compared with when they were viremia-negative (22% vs 17%; P = 0.659). Maternal side effects associated with VCV were mild and non-specific in most cases.. Our findings indicate that VCV treatment of pregnant women with primary CMV infection reduces the risk of maternal-fetal transmission of CMV and may be effective in cases with primary infection in the first and second trimesters. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Topics: Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies; Secondary Prevention; Valacyclovir; Viremia

Cytomegalovirus (CMV) infection increases mortality and morbidity following allogeneic hematopoietic stem-cell transplantation (alloHSCT). Universal antiviral prophylaxis with letermovir is effective but unsubsidized in Australia. Valaciclovir demonstrates anti-CMV activity in high doses, but few current real-world studies explore its use as primary prophylaxis in high-risk patients post-alloHSCT.. We performed a retrospective analysis of alloHSCT recipients at high risk of clinically significant CMV infection (cs-CMVi), defined as a plasma CMV DNA viral load of >400 IU/ml requiring preemptive therapy, or CMV disease. High-risk recipients were CMV seropositive and underwent T-cell depleted, haploidentical or umbilical cord stem-cell transplants. Consecutive patients transplanted from July 2018 to January 2020, treated with valaciclovir 2 g TDS from day +7 to +100 (HD-VALA), were compared to a historical cohort (July 2017-June 2018) who only received preemptive CMV therapy, and standard valaciclovir (SD-VALA) for varicella/herpes prophylaxis. We compared incidence of and time to cs-CMVi.. In the SD-VALA cohort (n = 27, median CMV follow-up duration 259 days), 23/27 (85%) developed cs-CMVi at a median of 39 days. For the HD-VALA cohort (n = 35, median CMV follow-up duration 216 days), 19/35 (54%) developed cs-CMVi, at a median of 68 days. Time to cs-CMVi was significantly longer in HD-VALA cohort (p < .0001). On multivariate analysis, HD VALA reduced the risk of cs-CMVi (HR 0.32, p = .0005).. In alloHSCT recipients at high risk for cs-CMVi, HD-VALA resulted in lower cumulative reactivation, and delayed reactivation, reducing requirement for preemptive CMV therapy in the early post-engraftment period.

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Humans; Retrospective Studies; Valacyclovir

Congenital cytomegalovirus infection is the most common congenital infection. Using a decision tree model, cost-effectiveness of maternal screening with subsequent prenatal valacyclovir treatment and newborn screening with neonatal valganciclovir treatment was evaluated. The incremental cost-effectiveness ratio (ICER) was calculated for (1) universal maternal antibody screening with prenatal valacyclovir treatment compared to targeted newborn screening, and (2) universal newborn screening with postnatal valganciclovir treatment compared to targeted newborn screening. We performed a one-way sensitivity analysis. Compared to targeted newborn screening, the ICERs for universal newborn screening and maternal screening were 2 966 296 Japanese Yen (JPY) (21 188 USD) and 1 026 984 JPY (7336 USD), respectively. In all scenarios in the one-way sensitivity analysis, the ICERs of the maternal screening and the universal newborn screening strategies were less than three gross domestic product per capita compared with the targeted newborn screening strategy. Both maternal and universal newborn screening strategies may be cost-effective than a targeted newborn screening program. The potential utility of the maternal screening with valacyclovir treatment strategy, while potentially cost effective in regions with lower baseline seroprevalence rates, requires further study as the modeling was based on limited evidence.

Topics: Cost-Benefit Analysis; Cytomegalovirus Infections; Female; Humans; Infant, Newborn; Japan; Neonatal Screening; Pregnancy; Seroepidemiologic Studies; Valacyclovir; Valganciclovir

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Pregnancy; Valacyclovir

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Iatrogenic Disease; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Valacyclovir

To assess the effectiveness, cost and cost-effectiveness of four screening strategies for first-trimester (T1) cytomegalovirus (CMV) primary infection (PI) in pregnant women in France.. In a simulated pregnant population of 800 000 (approximate number of pregnancies each year in France), using costs based on the year 2022, we compared four CMV maternal screening strategies: Strategy S1, no systematic screening (current public health recommendations in France); Strategy S2, screening of 25-50% of the pregnant population (current screening practice in France); Strategy S3, universal screening (current medical recommendations in France); Strategy S4, universal screening (as in Strategy S3) in conjunction with valacyclovir in case of T1 PI. Outcomes were total cost, effectiveness (number of congenital infections, number of diagnosed infections) and incremental cost-effectiveness ratio (ICER). Two ICERs were calculated, comparing Strategies S1, S2 and S3 in terms of euros (€) per additional diagnosis, and comparing Strategies S1 and S4 in € per avoided congenital infection.. Compared with Strategy S1, Strategy S3 enabled diagnosis of 536 more infected fetuses and Strategy S4 prevented 375 congenital infections. Strategy S1 was the least expensive strategy (€98.3m total lifetime cost), followed by Strategy S4 (€98.6m), Strategy S2 (€106.0m) and Strategy S3 (€118.9m). In the first analysis, Strategy S2 was dominated and Strategy S3 led to an additional €38 552 per additional in-utero diagnosis, compared with Strategy S1. In the second analysis, Strategy S4 led to an additional €893 per avoided congenital infection compared with Strategy S1, and was cost-saving compared with Strategy S2.. In France, current screening practice for CMV PI during pregnancy is no longer acceptable in terms of cost-effectiveness because this strategy was dominated by universal screening. Moreover, universal screening in conjunction with valacyclovir treatment would be cost-effective compared with current recommendations and is cost-saving compared with current practice. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Topics: Cost-Benefit Analysis; Cytomegalovirus; Cytomegalovirus Infections; Female; Fetal Diseases; Humans; Pregnancy; Pregnancy Trimester, First; Pregnant Women; Valacyclovir

A previous randomized placebo-controlled study found valaciclovir to be effective in reducing the rate of vertical cytomegalovirus transmission from mother to fetus. The better results in women infected in the first trimester compared to the periconception period were attributed to the timing of treatment. The aim of the present study was to evaluate valaciclovir efficacy in this setting using a revised protocol.. All pregnant women treated with valaciclovir in 2020-2022 who met the same criteria as in the original study were identified retrospectively from the database of the same medical center. Treatment, however, was initiated earlier: up to 9 weeks or 8 weeks from the presumed time of infection in women infected in the periconception period or the first trimester, respectively. The primary endpoint was rate of vertical cytomegalovirus transmission. Results were compared with the placebo arm in the previous study.. Among 178 women who completed valaciclovir treatment, amniocentesis was positive for cytomegalovirus in 14 women (7.9%), significantly (P < .001) lower compared with 14 of 47 (30%) in the placebo arm in the previous study. The proportion of positive amniocentesis in the valaciclovir was significantly lower than the placebo arm both among women infected in the first trimester (14/119 vs 11/23; odds ratio [OR] = 0.15; 95% confidence interval [CI]: .05-.45, P < .001), as well as among those infected in the periconception period (0/59 vs 3/24, OR = 0; 95% CI 0-.97, P = .02).. This study provides further evidence of the efficacy of valaciclovir in preventing vertical transmission of cytomegalovirus after primary maternal infection. Efficacy is improved with earlier treatment.

Topics: Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies; Secondary Prevention; Valacyclovir

Congenital cytomegalovirus (cCMV) is the leading cause of non-genetic sensorineural hearing loss and one of the main causes of neurological disability. Despite this, no universal screening programme for cCMV has been implemented in Spain. A recent study has shown that early treatment with valaciclovir, initiated in the first trimester and before the onset of signs in the fetus, reduces the risk of fetal infection. This finding favours the implementation of a universal screening programme for cCMV.The aim of this study is to evaluate the performance of a universal screening programme for cCMV during the first trimester of pregnancy in a primary care setting.. This is an observational multicentre cohort study. The study will be conducted in four primary care settings from the Northern Metropolitan Barcelona area and three related hospitals and will last 3 years and will consist of a recruitment period of 18 months.In their first pregnancy visit, pregnant women will be offered to add a CMV serology test to the first trimester screening tests. Pregnant women with primary infection will be referred to the reference hospital, where they will continue treatment and follow-up according to the clinical protocol of the referral hospital, which includes treatment with valacyclovir. A CMV-PCR will be performed at birth on newborns of mothers with primary infection, and those who are infected will undergo neonatal follow-up for at least 12 months of life.For the analysis, the acceptance rate, the prevalence of primary CMV infections and the CMV seroprevalence in the first trimester of pregnancy will be studied.. Ethical approval was obtained from the University Institute Foundation for Primary Health Care Research Jordi Gol i Gurina Ethics Committee 22/097-P dated 27 April 2022.

Topics: Cohort Studies; Cytomegalovirus Infections; Female; Humans; Infant, Newborn; Multicenter Studies as Topic; Observational Studies as Topic; Parturition; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Seroepidemiologic Studies; Valacyclovir

Patients undergoing haploidentical or mismatched unrelated donor (haplo/MMUD) allogeneic hematopoietic cell transplantation (alloHCT) receiving post-transplant cyclophosphamide (PTCy) are at high risk of cytomegalovirus (CMV) infection. Experience with letermovir (LET) in this population is limited. This single center retrospective cohort study compared CMV and transplant outcomes between LET and a historical control with high-dose valacyclovir (HDV) prophylaxis in adults undergoing haplo/MMUD alloHCT. Thirty-eight CMV seropositive patients were included, 19 in each arm. LET reduced the incidence of CMV infection (5% vs. 53%, RR 0.01, 95% CI 0.014-0.71,

Topics: Acetates; Adult; Cyclophosphamide; Cytomegalovirus; Cytomegalovirus Infections; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Quinazolines; Retrospective Studies; Unrelated Donors; Valacyclovir

Recent studies have suggested a possible benefit of valaciclovir prophylaxis to prevent vertical transmission after a positive serologic screen for primary maternal cytomegalovirus infection during pregnancy, although its cost-effectiveness remains uncertain.. This study aimed to determine the circumstances under which universal first-trimester maternal serologic screening for maternal cytomegalovirus infection, with valaciclovir prophylaxis to prevent congenital cytomegalovirus, is cost-effective.. This study was a decision analysis from the perspective of the pregnant person to assess whether universal maternal screening in the first trimester of pregnancy, with subsequent valaciclovir prophylaxis (8 g/day from the time of positive serologic screen for primary maternal cytomegalovirus infection to 21 weeks of gestation) for those who are acutely infected, is cost-effective compared with usual care (ie, no routine serologic screening but with amniocentesis if midtrimester sonographic findings suggest cytomegalovirus). For baseline estimates, this study assumed a 35% risk of congenital cytomegalovirus after primary maternal infection and a 71% risk reduction with valaciclovir. This study varied valaciclovir's efficacy to identify whether and at what threshold universal screening would be estimated to be cost-effective, compared with usual care. Monte Carlo analyses were performed. A willingness-to-pay threshold of $100,000/quality-adjusted life year was used to define cost-effectiveness.. Under base case estimates, first-trimester universal screening and valaciclovir prophylaxis for seropositive pregnant persons with acute cytomegalovirus infection were not cost-effective, with a cost of $137,854 per maternal quality-adjusted life year but resulted in 14 fewer children affected with cytomegalovirus per 100,000 pregnancies compared with usual care. In 1-way sensitivity analysis, universal screening and treatment were estimated to be the cost-effective strategy if the incidence of primary maternal cytomegalovirus infection exceeds 2.6%, the baseline risk of vertical transmission of cytomegalovirus without prophylaxis is greater than 36.8%, and the risk reduction of vertical transmission of cytomegalovirus with valaciclovir prophylaxis exceeds 75.9%. In Monte Carlo analyses, first-trimester universal serologic screening with valaciclovir prophylaxis was estimated to be the cost-effective strategy in 46.8% of runs.. Universal first-trimester serologic screening with valaciclovir prophylaxis is not the cost-effective strategy for antenatal management of cytomegalovirus under the base case estimates. Although universal screening is cost-effective in certain circumstances when the efficacy of valaciclovir exceeds the base case, that result was not robust to variation of estimates across their reasonable ranges. These data can inform future studies to evaluate screening and treatment to prevent congenital cytomegalovirus.

Topics: Child; Cost-Benefit Analysis; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Valacyclovir

Recurrent congenital cytomegalovirus infections in consecutive pregnancies are rarely reported. Due to the risk of fetal infection from preconception maternal infection, a 6-month interval after primary maternal infection is generally advised before a new conception. Recently, high-dose valacyclovir treatment was shown to prevent fetal infection in first trimester primary infections. We present a case of first trimester primary infection treated with high-dose valacyclovir but resulting in polymerase chain reaction-confirmed fetal infection. Cytomegalovirus-specific immunoglobulin G titers remained very low during treatment and rose only after cessation of antiviral treatment. Six months after primary seroconversion, in a sequential pregnancy, recurrent fetal infection was diagnosed and resulted in severe fetal sequella. Whole genome sequencing of both amniotic fluid isolates proved them to be identical. Both pregnancies were terminated. We hypothesize that valacyclovir treatment, although unsuccessful in preventing fetal infection, had delayed the adaptive maternal immune response and might have contributed to fetal infection during the sequential pregnancy. We suggest that a longer delay might be warranted after valacyclovir treatment and before a new conception.

Topics: Cytomegalovirus; Cytomegalovirus Infections; Female; Fetal Diseases; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Valacyclovir

(1) Background: What is the role of serum CMV PCR in the diagnosis of recent primary infection (PI) in pregnant women when IgG avidity is uninformative? (2) Methods: Retrospective cohort study to compare serum versus whole blood CMV PCR. (a) Qualitative assessment: CMV PCR was performed on 123 serum samples and 74 whole blood samples collected from 132 pregnant women with recent CMV PI. PCR positivity rate was used to calculate sensitivity in serum and whole blood. (b) Quantitative assessment: CMV PCR was performed on 72 paired samples of serum and whole blood collected on the same day from 57 patients. (3) Results: In pregnant women, PCR positivity rate was 89% for serum samples versus 100% in whole blood in the case of very recent PI (<15 days), but only 27% in serum versus 68% in whole blood for PI occurring from 6 weeks to 3 months before. Comparing CMV viral loads between serum and whole blood, we determined the limit of CMV DNA detection in serum as 3 log copies/mL (whole blood equivalent). (4) Conclusions: Serum CMV PCR is reliable in confirming PI in cases when only IgM is detected. It is therefore a valuable tool in introducing valaciclovir treatment as early as possible to prevent mother-to-child CMV transmission.

Topics: Antibodies, Viral; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Immunoglobulin G; Immunoglobulin M; Infectious Disease Transmission, Vertical; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Infectious; Pregnant Women; Retrospective Studies; Valacyclovir

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Humans; Kidney Transplantation; Valacyclovir

The reactivation of CMV (Cytomegalovirus) in renal transplant recipients may be manifested across a clinical spectrum from asymptomatic viraemia to organ rejection. The purpose of this study is to evaluate the patients who have experienced CMV infection after renal transplantation in the last twelve years, and to assess the efficacy of valacyclovir.. Renal transplant recipients' demographic, clinical and laboratory data were evaluated retrospectively between 2006-2018. Valaciclovir was given at the standard prophylaxis dose of 2000 mg/daily. CMV Polymerase Chain reaction (PCR) was performed in 2-week intervals until 1 year after transplantation, and upon any symptoms attributable to CMV.. The entire study group had D+/R+ (donor-positive, recipient-positive) serological status of the CMV virus. 171 (59.2%) patients had only CMV infection, 60 (20.8%) had overall CMV antigen positivity until the end of the follow-up period and 7 (2.4%) patients had CMV disease. Rejection episodes were diagnosed in 31 (10.8%) patients; 20 (64.5%) of those were PCR positive for CMV; mortality rate was 12 (4.2%) but those who died had a non-CMV related disease.. Valaciclovir may be preferred in prophylaxis instead of valganciclovir as we used in our study since valganciclovir has prolonged treatment time, rapid development of drug resistance, drug toxicity and high cost.

Topics: Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunoglobulin G; Kidney Transplantation; Retrospective Studies; Valacyclovir; Valganciclovir

Congenital cytomegalovirus (CMV) infection is one of the most common during pregnancy. The infection, particularly in the first trimester, is associated with important sequelae in up to half of the children. Valaciclovir and immunoglobulin have been tested separately for the treatment of fetal CMV infection with relative success. Nevertheless, there is no experience with the simultaneous use of both therapies.. Combination therapy with immunoglobulin and valaciclovir may be a useful alternative in CMV fetal infection, particularly if changes in cerebral echography or high VL in the amniotic fluid are present.

Topics: Cytomegalovirus Infections; Female; Fetal Diseases; Humans; Immunoglobulins, Intravenous; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Pregnant Women; Valacyclovir

Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Renal Insufficiency; Secondary Prevention; Valacyclovir

Topics: Antiviral Agents; Cytomegalovirus Infections; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Valacyclovir

Cytomegalovirus (CMV) infection causes morbidity and mortality after allogeneic haematopoietic stem cell transplantation (HSCT). We investigated whether prophylaxis with high dose valaciclovir is effective at reducing the incidence of clinically significant CMV infection (csCMVi) within six months of allogeneic HSCT. Consecutive allogeneic HSCT recipients who received 2g valaciclovir orally four times daily from transplant until day 100 (prophylaxis group) were compared to subsequent patients who received no CMV prophylaxis (control group). Forty-nine patients in the prophylaxis group and 59 in the control group were included. The cumulative incidence of csCMVi at 6 months was 20% (95% confidence interval (CI): 9%-27%) in the prophylaxis group and 39% (95% CI: 26%-47%) in the control group (P = .009). There was no CMV disease in the prophylaxis group and three cases in the control group. There was no difference in time to neutrophil or platelet recovery nor graft failure between groups. On multivariable analysis, lack of high dose valaciclovir prophylaxis, positive recipient CMV IgG and age were associated with greater likelihood of csCMVi. There was no significant difference in acute graft versus host disease, non-relapse mortality or overall survival between groups. In this retrospective cohort study, high dose valaciclovir prophylaxis resulted in a lower incidence of csCMVi within six months of HSCT.

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Humans; Retrospective Studies; Transplant Recipients; Transplantation, Homologous; Valacyclovir

Cytomegalovirus (CMV) maternal primary infection (MPI) in early pregnancy is the main risk factor for congenital CMV (cCMV) infection with long-term sequelae. Our aim was to evaluate, in a single center offering CMV serology screening at 11-14 gestational weeks, secondary prevention of cCMV by administration of high-dosage maternal oral valacyclovir (VACV) in the first trimester of pregnancy.. This was a case-control study in a longitudinal cohort of pregnancies with CMV-MPI diagnosed prior to 14 weeks of gestation by serology screening (immunoglobulin (Ig) M and IgG measurement and IgG avidity) between 2009 and 2020. From October 2019 onwards, all women presenting at our center with MPI before 14 weeks' gestation were offered treatment with high-dosage oral VACV (8 g/day, 4 g twice/day). We used propensity score matching to compare fetal infection rates in cases treated with maternal oral VACV (8 g/day) with those in untreated controls. Fetal infection was assessed following amniocentesis at 17-22 weeks of gestation, by polymerase chain reaction (PCR) analysis of amniotic fluid for viral DNA.. Of 310 cases of CMV-MPI identified, 269 underwent amniocentesis for PCR. Of these, 66 were offered, and 65 accepted, treatment with VACV. From the remaining untreated cases, we selected 65 controls, matched for proportion of periconceptional infections and gestational age at amniocentesis. VACV was initiated at a median gestational age of 12.71 (interquartile range (IQR), 10.00-13.86) weeks and the median duration of treatment was 35 (IQR, 26-54) days. On multivariate logistic regression, fetal infection was lower in the treated group (odds ratio, 0.318 (95% CI, 0.120-0.841); P = 0.021). One treated patient developed acute renal failure 4 weeks after initiation of VACV therapy, but this resolved within 5 days after treatment was stopped.. This study confirms the acceptability, tolerance and benefit of secondary prevention by VACV of cCMV infection in a clinical setting with a well-established routine maternal serum screening policy in the first trimester of pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Topics: Adult; Amniocentesis; Antiviral Agents; Case-Control Studies; Cytomegalovirus; Cytomegalovirus Infections; Female; Fetal Diseases; Gestational Age; Humans; Infectious Disease Transmission, Vertical; Logistic Models; Longitudinal Studies; Maternal Serum Screening Tests; Odds Ratio; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, First; Propensity Score; Secondary Prevention; Treatment Outcome; Valacyclovir

Not available.

Topics: Antiviral Agents; Cytomegalovirus Infections; Humans; Infant, Newborn; Italy; Valacyclovir

Topics: Acute Kidney Injury; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications; Valacyclovir

Topics: Aged; Antiviral Agents; Colitis; Colonic Diseases; Colonoscopy; Colostomy; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Infusions, Intravenous; Intestinal Fistula; Valacyclovir

No treatment is currently approved for cytomegalovirus infection in pregnancy. Valacyclovir has been studied in symptomatic cytomegalovirus infected fetuses and seems to reduce the risk of serious sequelae.. We used off-label valacyclovir on pregnant women with primary cytomegalovirus infection to reduce the risk of fetal infection.. We treated 12 pregnant women with 8 g/day valacyclovir after diagnosis of cytomegalovirus infection until amniocentesis. We continued treatment until delivery in case of fetal infection. We periodically performed serology and virology tests on the women from referral until delivery and monitored them for adverse effects while on treatment. All women underwent late amniocentesis. We followed up infants for 5-28 months.. At the time of amniocentesis, we observed a transmission rate of 17 %, and at birth we observed a transmission rate of 42 %. Two women with negative amniocentesis and infected newborns had viremia reactivation after valacyclovir discontinuation. We observed no symptomatic infections at birth and one isolated sensory-neural hearing loss at follow-up.. This is the first series of antiviral treatment in women with a diagnosis of cytomegalovirus infection before amniocentesis. Valacyclovir may control cytomegalovirus infection while it is administered and reduce transmission at amniocentesis. Late transmission after treatment discontinuation is a risk. We advocate the need for a controlled trial of valacyclovir therapy starting from diagnosis of maternal infection until delivery, regardless of prenatal diagnosis of infection.

Topics: Antibodies, Viral; Antiviral Agents; Child, Preschool; Cytomegalovirus Infections; Female; Gestational Age; Humans; Infant; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Valacyclovir

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

Topics: Acyclovir; Antiviral Agents; Bayes Theorem; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Male; Organ Transplantation; Valacyclovir; Valganciclovir

Topics: Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Female; Humans; Infections; Infectious Disease Transmission, Vertical; Pregnancy; Secondary Prevention; Valacyclovir

Topics: Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Valacyclovir

Anti-thymocyte globulin (ATG) treatment for acute T-cell mediated rejection (TCMR) can increase the risk of cytomegalovirus (CMV) infection. We aimed to evaluate the effect of valacyclovir prophylaxis against CMV infection after ATG administration as anti-rejection therapy.. We retrospectively analyzed 55 kidney transplant recipients (KTRs) receiving ATG for steroid resistant TCMR. In all KTRs, we used intravenous ganciclovir during ATG injection. In 34 KTRs treated before July 2013, we performed preemptive therapy for CMV infection after ATG therapy. They were regarded as the historic control group (CONT). After July 2013, we used valacyclovir maintenance for 1 month after ATG therapy in 21 patients (VAL). The primary outcome was the incidence of CMV infection, and the secondary outcomes were subsequent acute rejection, and graft and patient outcome.. Valacyclovir prophylaxis significantly reduced the incidence of CMV infection (VAL, 9.6% vs. CONT, 67.6%; p < 0.001), and CMV-free survival rate was higher in the VAL group compared to the CONT group (p = 0.009). In the VAL group, two cases of CMV infection were limited to CMV viremia, but CMV disease or syndrome (n = 3) was detected in the CONT group. There was no difference in graft failure (CONT, 70.5% vs. VAL, 47.6%; p = 0.152), incidence of subsequent rejection after ATG treatment (CONT, 41.1% vs. VAL, 33.3%; p = 0.776), and graft or patient survival between the two groups. There were no major adverse events associated with valacyclovir prophylaxis.. In conclusion, valacyclovir prophylaxis is effective in the prevention of CMV infection after ATG treatment for steroid resistant TCMR.

Topics: Adult; Antilymphocyte Serum; Antiviral Agents; Cytomegalovirus Infections; Female; Graft Rejection; Humans; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Valacyclovir

Cytomegalovirus (CMV) is the main cause of congenital viral infections. Current guidelines do not include any recommendation about antenatal treatment. Most studies that evaluate the efficacy of valaciclovir aim to treat infected symptomatic fetus but the benefit of anti-CMV therapy remains unclear.. We report the case of cytomegalovirus seroconversion during the second trimester of pregnancy. Early treatment with valaciclovir was introduced, associated with a close monitoring of maternal CMV viremia. The virus was no longer detected in maternal blood soon after the beginning of antiviral therapy. Valaciclovir was stopped at 24 + 5 WG after negative prenatal diagnosis but CMV viremia was still monitored in maternal blood until the end of pregnancy.. The neonate was not infected and remained asymptomatic. It suggests that early treatment with valaciclovir 8 g per day could be effective in quickly reducing maternal viral load and lowering the risk of vertical CMV transmission.

Topics: Adult; Antibodies, Viral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Fetal Diseases; Humans; Immunoglobulin G; Immunoglobulin M; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Second; Prenatal Diagnosis; Seroconversion; Valacyclovir; Viral Load; Viremia

A 42-year-old woman with a history of cholangiocarcinoma on adjuvant chemotherapy with capecitabine presented with painless haematochezia. She was found to have an isolated twenty-five mm ulcer in the ascending colon. Biopsies of the ulceration demonstrated typical cytomegalovirus (CMV) inclusions and her peripheral blood CMV PCR was significantly elevated. This is an unusual case of a solitary proximal colon ulcer. Non-steroidal anti-inflammatory drugs, inflammatory bowel disease and malignancy, are the most frequent causes of isolated ulcers in the proximal colon. Gastrointestinal (GI) CMV disease most commonly causes CMV colitis and is considered rare outside of the transplant population and other severely immunosuppressed patient groups. Patients who have received chemotherapy may also be at risk for GI CMV disease. The diagnosis should be suspected in patients who present with haematochezia or watery diarrhoea within a broad window of time after receiving chemotherapy.

Topics: Adult; Antimetabolites, Antineoplastic; Antiviral Agents; Bile Duct Neoplasms; Capecitabine; Chemotherapy, Adjuvant; Cholangiocarcinoma; Colitis; Colon, Ascending; Cytomegalovirus Infections; Female; Gastrointestinal Hemorrhage; Humans; Immunocompromised Host; Pancreaticoduodenectomy; Risk Factors; Ulcer; Valacyclovir

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

Topics: Cord Blood Stem Cell Transplantation; Cytomegalovirus; Cytomegalovirus Infections; Fetal Blood; Humans; Incidence; Transplantation, Homologous; Valacyclovir

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Fetus; Humans; Valacyclovir; Valine

Cytomegalovirus infection is a major cause of morbidity and mortality in solid-organ transplant. Low doses of valacyclovir have been administered as cytomegalovirus prophylaxis in our institution for years. To the best of our knowledge, there is no published study of a low-dose regimen for cytomegalovirus prophylaxis in heart transplant patients. Therefore, our aim was to determine the results of low doses of valacyclovir in heart transplant.. Between September 2006 and December 2014, sixty-eight patients underwent orthotopic heart transplants. All of the patients received triple immunosuppressive therapy after surgery. During the next 6 months, sulfamethoxazole/trimethoprim was administered for Pneumocystis jiroveci pneumonia, and toxoplasmosis. Additionally all patients received valacyclovir hydrochloride (1000 mg/d, oral) for cytomegalovirus prophylaxis and nystatin oral rinse for prophylaxis of fungal infections.. There was only 1 cytomegalovirus infection at follow-up. The patient had cytomegalovirus pneumonia at 17-month follow-up. In response to treatment with 1-week intravenous ganciclovir, the patient was discharged with a further 6-month oral valacyclovir therapy (1000 mg/d).. In this study, we hypothesized that daily use of low-dose valacyclovir (1000 mg/d) is not only sufficient for cytomegalovirus prophylaxis but also beneficial in terms of cost.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Opportunistic Infections; Pneumonia, Viral; Risk Factors; Time Factors; Treatment Outcome; Valacyclovir; Valine; Virus Activation; Young Adult

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.. 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.. 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.. VACV prophylaxis for CMV is associated with a significant 44% lower cost than vGCV at the first year after renal transplantation.

Topics: Acyclovir; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Follow-Up Studies; Ganciclovir; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Valacyclovir; Valganciclovir; Valine

A 36-year-old woman was admitted to our hospital for further examination of an acute febrile illness with liver dysfunction. A peripheral blood smear displayed atypical lymphocytes. Cytomegalovirus (CMV) mononucleosis was diagnosed based on the detection of CMV-specific IgM and conventional CMV pp65 antigen. The physical examination on admission revealed signs of lower motor neuron right facial palsy. There were no significant cerebrospinal fluid findings, nor were there other neurological abnormalities. After receiving a short-course of oral corticosteroids, the patient gradually recovered from the facial paralysis. A one-month follow-up examination indicated that she had fully recovered neurologically, showing disappearance of CMV-DNA and a significant increase in the anti-CMV IgG titer. To our knowledge, there has been only one previous report describing CMV as the cause of an isolated facial palsy combined with CMV mononucleosis.

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Biomarkers; Cytomegalovirus; Cytomegalovirus Infections; Facial Paralysis; Female; Humans; Immunoglobulin M; Infectious Mononucleosis; Phosphoproteins; Prednisolone; Treatment Outcome; Valacyclovir; Valine; Viral Matrix Proteins

Topics: Acyclovir; Adult; Antiviral Agents; Crohn Disease; Cytomegalovirus Infections; Fever; Humans; Ilium; Male; Valacyclovir; Valine

A 73-year-old woman with a history of deceased donor kidney transplantation and a recent cytomegalovirus (CMV) infection, presented to the emergency department with an altered mental status. She was found to have varicella zoster virus VZV encephalitis based on cerebrospinal fluid analysis and was treated successfully with intravenous valaciclovir with an improvement in her mental status. A review of the literature shows very few case reports on patients with kidney transplantation developing VZV encephalitis. A few case reports and studies report an association between CMV and VZV infection. In these patients, CMV infection can cause a marked decline in immunity and this predisposes them to other infections. Such associations have also been reported between other types of virus infections from the Herpesviridae family. The risk of disseminated VZV infection increases in the presence of CMV infection.

Topics: Acyclovir; Aged; Antiviral Agents; Cytomegalovirus Infections; Diagnosis, Differential; Encephalitis, Varicella Zoster; Female; Herpesvirus 3, Human; Humans; Kidney Transplantation; Magnetic Resonance Imaging; Valacyclovir; Valine

Many children receiving a kidney transplant are seronegative for CMV and therefore, highly susceptible to a primary CMV infection. This study aims at evaluating incidence, time of occurrence, and severity of CMV infection in the first year post-transplantation in relation to different types of CMV prophylaxis. Transplantations in three centers in the Netherlands between 1999 and 2010 were included. Retrospective, observational, multicenter study. Clinical data and PCR measurements of CMV were collected. Prophylaxis in high-risk patients (CMV serostatus D+R-) consisted of (val)ganciclovir during three months, or acyclovir plus CMV immunoglobulin at a former stage. Intermediate-risk patients (R+) received (val)acyclovir, or acyclovir plus CMV immunoglobulin at a former stage. Low-risk patients (D-R-) did not receive prophylaxis. Infection was defined as CMV PCR above 50 geq/mL plasma or whole blood, a clinically relevant infection above 1000 geq/mL. One hundred and fifty-nine transplantations were included. CMV infection was documented for 41% of high-risk, 24% of intermediate-risk, and 13% of low-risk patients, in the latter two groups typically during the first three months. The infection rate was highest in the high-risk group after cessation of valganciclovir prophylaxis. Valganciclovir provided better protection than did acyclovir + CMV immunoglobulin. Adding an IL2-receptor blocker to the immunosuppressive regimen did not affect the infection rate. Acute graft rejection was not related with CMV infection. Valganciclovir prophylaxis effectively prevents CMV infection in high-risk pediatric kidney recipients, but only during prophylaxis. Valacyclovir prophylaxis in intermediate-risk patients is less effective.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Disease-Free Survival; Ganciclovir; Humans; Immunoglobulins; Immunosuppressive Agents; Infant; Kidney Transplantation; Netherlands; Polymerase Chain Reaction; Receptors, Interleukin-2; Renal Insufficiency; Retrospective Studies; Risk; Valacyclovir; Valganciclovir; Valine

Topics: Acyclovir; Adult; Allografts; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Valacyclovir; Valine

Topics: Acyclovir; Aged; Antibodies, Monoclonal, Murine-Derived; Antiviral Agents; Biopsy; Cytomegalovirus Infections; Drug Therapy, Combination; Glucocorticoids; Herpes Simplex; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Pemphigus; Prednisolone; Rituximab; Skin; Treatment Outcome; Valacyclovir; Valine

Cytomegalovirus (CMV) infection leads to the development of adaptive and humoral immune responses that are among the largest for any pathogen, and intriguingly, the magnitude of the immune response increases with age, a phenomenon termed "memory inflation." Elevated CMV-specific immunity has been correlated with an increased mortality rate in elderly individuals and with impaired vaccination responses. The latent phase of CMV infection is characterized by intermittent episodes of subclinical viral reactivation and the production of immunogenic transcripts that may maintain memory inflation of virus-specific cytotoxic lymphocytes. However, the relative importance of CMV reactivation in the development of memory inflation is uncertain, as is the potential for antiviral treatment to reverse this effect. Here, we administered valaciclovir for up to 12 months in mice with established murine CMV (MCMV) infection. Treatment reduced the magnitude of the MCMV-specific CD8(+) T-lymphocyte response by 80%, and the residual MCMV tetramer-specific lymphocytes exhibited a less differentiated phenotype. In addition, latent MCMV infection suppressed the proportion of naïve CD8(+) T cells by 60% compared to antiviral-treated mice or MCMV-negative animals. Furthermore, treatment led to a reduction in influenza A viral loads following a challenge in elderly MCMV-infected animals and also reduced the differentiation of influenza virus-specific cytotoxic lymphocytes. These observations demonstrate that MCMV-specific memory inflation is maintained by viral replication and that therapeutic intervention could lead to improved immune function.

Topics: Acyclovir; Animals; Antiviral Agents; CD8-Positive T-Lymphocytes; Cytomegalovirus Infections; Female; Immunologic Memory; Mice; Mice, Inbred C57BL; Muromegalovirus; Valacyclovir; Valine; Virus Activation; Virus Latency

Cytomegalovirus (CMV) remains an important pathogen in transplant patients, and valacyclovir (VACV) prophylaxis 8 g/day has been used in high-risk CMV-seromismatched [D+/R-] renal transplant patients to decrease CMV disease. Neurotoxic adverse effects have limited its use, and the aim of the present study was to retrospectively evaluate low-dose VACV prophylaxis, 3 g/day for 90 days after transplantation, in 102 D+/R- renal transplant patients.. We compared patient and graft survival rates up to 5 years after transplantation with the data from the Collaborative Transplant Study Group (CTS) database. The incidence of CMV disease, rejection and neurotoxic adverse effects was analyzed up to 1 year after transplantation.. The patient and graft survival rates up to 5 years were comparable with those derived from the CTS. CMV disease was diagnosed in 25% of the patients and 2% developed tissue-invasive CMV disease. The rejection frequency was 22% and neurotoxic adverse effects were seen in 2% of the patients.. Low-dose VACV prophylaxis (3 g/day) for 90 days post-transplantation results in high patient and graft survival rates and reduces the incidence of CMV disease. Neurotoxic adverse effects are minimal. We believe that low-dose VACV prophylaxis should be considered to form one of the arms in future prospective comparison studies for the prevention of CMV disease in the high-risk D+/R- population of renal transplant patients.

Topics: Acyclovir; Adult; Antibiotic Prophylaxis; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prognosis; Renal Insufficiency, Chronic; Retrospective Studies; Survival Rate; Time Factors; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Azathioprine; Colitis; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunosuppressive Agents; Valacyclovir; Valine; Young Adult

Many species of tsetse flies are infected with a virus that causes salivary gland hypertrophy (SGH) symptoms associated with a reduced fecundity and fertility. A high prevalence of SGH has been correlated with the collapse of two laboratory colonies of Glossina pallidipes and colony maintenance problems in a mass rearing facility in Ethiopia. Mass-production of G. pallidipes is crucial for programs of tsetse control including the sterile insect technique (SIT), and therefore requires a management strategy for this virus. Based on the homology of DNA polymerase between salivary gland hypertrophy virus and herpes viruses at the amino acid level, two antiviral drugs, valacyclovir and acyclovir, classically used against herpes viruses were selected and tested for their toxicity on tsetse flies and their impact on virus replication. While long term per os administration of acyclovir resulted in a significant reduction of productivity of the colonies, no negative effect was observed in colonies fed with valacyclovir-treated blood. Furthermore, treatment of a tsetse colony with valacyclovir for 83 weeks resulted in a significant reduction of viral loads and consequently suppression of SGH symptoms. The combination of initial selection of SGHV-negative flies by non-destructive PCR, a clean feeding system, and valacyclovir treatment resulted in a colony that was free of SGH syndromes in 33 weeks. This is the first report of the use of a drug to control a viral infection in an insect and of the demonstration that valacyclovir can be used to suppress SGH in colonies of G. pallidipes.

Topics: Acyclovir; Animals; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Tsetse Flies; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Kidney Transplantation; Male; Valacyclovir; Valganciclovir; Valine

Human Cytomegalovirus is a commonly identified herpesvirus that establishes a state of latent infection in the majority of the population by adulthood. A coordinated immune response involving both the innate and adaptive immune system prevents active viral replication and disease. Cellular immunity appears particularly important to control of viremia requiring both a CMV-specific CD4+ and CD8+ T cell response. Solid organ transplant recipients are particularly susceptible to CMV related disease due to the immunosuppression necessary to prevent organ rejection, with patients receiving T cell depleting therapies being at highest risk. The deleterious outcomes of CMV in organ transplant recipients result from both direct cytopathic and indirect immune-modulatory effects of CMV viral replication. The recognition of the negative effects of CMV in solid organ transplantation has resulted in the routine prophylaxis of organ recipients with antiviral nucleoside analogues. The appropriate duration of therapy is still controversial although guidelines do exist. The ability to assay an individual immune response to CMV should allow for tailored duration of therapy in the future.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Graft Rejection; Humans; Immunity, Cellular; Immunosuppressive Agents; Risk Factors; Tissue Transplantation; Valacyclovir; Valganciclovir; Valine

To describe an atypical case of cytomegalovirus (CMV) endotheliitis in a 74-year-old man who presented with chronic corneal edema without keratic precipitates (KPs) and intraocular pressure (IOP) elevation.. Case report.. A complete ophthalmologic examination was performed. Polymerase chain reaction was used to test for herpes simplex virus, varicella zoster virus, and CMV DNA in aqueous humor samples to rule out viral endotheliitis.. Severe bullous keratopathy was found in the temporal part of the cornea without KPs or elevated IOP. CMV DNA was detected. Corneal edema subsided with oral valganciclovior.. CMV endotheliitis may present as corneal edema that lacks typical features, such as KPs or elevated IOP.

Topics: Acyclovir; Aged; Antiviral Agents; Corneal Edema; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Endothelium, Corneal; Ganciclovir; Humans; Intraocular Pressure; Keratitis, Herpetic; Male; Prednisolone; Valacyclovir; Valganciclovir; Valine; Visual Acuity

Cytomegalovirus (CMV) remains an important cause of disease in renal transplant recipients. Prophylaxis is effective in reducing disease; however, the optimal regimen remains uncertain. We assessed the efficacy of low-dose valaciclovir (3 months) and intravenous CMV immunoglobulin in the prevention of CMV disease in CMV-negative recipients of kidneys from CMV-positive donors (D+/R-).. A single-centre, retrospective study examining the incidence of CMV disease and patient and graft survival in all patients transplanted between October 2000 and November 2004.. Among 203 renal transplant recipients, 46 were D+/R- (22.7%) and received prophylaxis. Of the 203 recipients, 21 (10.3%) developed CMV disease over a four-year follow-up period. Within the D+/R- group, CMV disease occurred in 15.2% of patients at 6 months (7/46), and 21.7% at 4 years (10/46). Of the 10 D+/R- patients who developed CMV disease, six were inadvertently on a dose of valaciclovir below that dictated by protocol arising from a failure to increase dosage in parallel with improving recipient renal function. In the D+/R- recipients where the protocol was adhered to, the incidence of CMV disease was 5% (2/40) at 6 months, and 10% (4/40) at 4 years.. Low-dose valaciclovir with CMV immunoglobulin was as efficacious in preventing CMV disease as other published regimens, including those with full-dose valaciclovir and valganciclovir. There was a low incidence of CMV disease beyond 6 months. Outcomes could be improved by ensuring appropriate dose adjustment following changes in renal function.

Topics: Acyclovir; Adolescent; Adult; Aged; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunoglobulins; Incidence; Kidney Transplantation; Male; Middle Aged; Retrospective Studies; Tissue Donors; Valacyclovir; Valine; Young Adult

Antiviral prophylaxis against cytomegalovirus has been associated with reduced risk of allograft rejection and improved allograft survival after renal transplantation. This phenomenon might not be fully explained by preventing the indirect effects of cytomegalovirus. The effect of antiviral agents on lymphocyte function in patients treated with modern immunosuppression has not been studied to date.. Adult renal transplant recipients were assigned to 3-month prophylaxis with either valganciclovir (900 mg once daily; n=19) or valacyclovir (2 g four times daily; n=17) as part of an ongoing randomized trial. Subsets of lymphocytes, lymphocyte proliferation and/or cytokine production after in vitro mitogen stimulation were evaluated at the end of prophylaxis and 1 month after withdrawal of antiviral drugs.. Lymphocyte proliferation was significantly decreased both after phytohemagglutinine (25% ±15% versus 32% ±18%; P=0.025) and concanavalin A stimulation (17% ±9% versus 25% ±16%; P=0.011) during valganciclovir, but not valacyclovir therapy. Moreover, a lower activated T-cell count (CD3(+)HLA-DR(+) cells) was noted in valganciclovir-treated patients (13% ±10% versus 17% ±12% of total CD3(+) T-cells; P=0.005).. Valganciclovir suppresses lymphocyte proliferation and activation in patients after renal transplantation.

Topics: Acyclovir; Adult; Antiviral Agents; Cell Proliferation; Cells, Cultured; Concanavalin A; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Lymphocyte Activation; Lymphocyte Count; Male; Middle Aged; Phytohemagglutinins; T-Lymphocyte Subsets; Valacyclovir; Valganciclovir; Valine

We followed up 550 primary kidney transplant recipients in an observational retrospective cohort to evaluate the impact of three consecutive cytomegalovirus (CMV) prevention strategies. In period 1 (1996-2000; n = 190), no anti-CMV prophylaxis was given; in period 2 (2000-2004; n = 173), 6-month valacyclovir was given and in period 3 (>2004; n = 187), 6-month valganciclovir was given. Cytomegalovirus disease significantly decreased from 33.2% in period 1 to 13.9% in period 2 and to 8.6% in period 3; onset was significantly prolonged with valganciclovir (228 days) compared with valacyclovir (93 days) and with no prophylaxis (33 days). After Cox regression adjustments, both valganciclovir and valacyclovir were similarly protective factors for CMV disease. Cytomegalovirus diseases encountered in both valacyclovir and valganciclovir groups were primary infections (79.2 and 93.8% respectively) as compared with a significant low number (39.7%) in the nonprophylaxis group. Two cases of valganciclovir resistance were recorded in the valganciclovir group and no resistance was seen with valacyclovir. A significantly reduced incidence of other herpes viruses was only observed with valganciclovir. Valganciclovir was better tolerated than valacyclovir and this long-term prophylaxis was applicable to 85% of patients. Longer follow-up of valganciclovir or valacyclovir prophylaxis is still required to appreciate its impact on graft and patient survivals, as well as other indirect effects, in the mycophenolate mofetil and calcineurin inhibitor immunosuppressive era.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Female; Follow-Up Studies; Ganciclovir; Graft Survival; Humans; Incidence; Injections, Intravenous; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Prodrugs; Retrospective Studies; Survival Rate; Time Factors; Treatment Outcome; Valacyclovir; Valganciclovir; Valine

Posttransplant leukopenia is frequently observed in renal transplant. Granulocyte colony-stimulating factor controls the production of functional neutrophils and their release into peripheral blood. Granulocyte colony-stimulating factor has been widely and frequently used for many conditions and disorders in the field of hematology and oncology.. We present the cases of valacyclovir-related and valganciclovir-related neutropenia in 2 renal transplant recipients.. Both cases had renal transplants from live donors. The first one was an 18-year-old man. Laboratory investigations revealed his leukocyte count as 1.7 x 10(9)/L. The patient was using mycophenolate mofetil, cyclosporine, and valganciclovir. Mycophenolate mofetil was stopped because he had neutropenia, and later, valganciclovir was also stopped because the neutropenia persisted. Because the neutropenia did not recover after we discontinued valganciclovir, the patient was administered granulocyte colony-stimulating factor. The neutrophil count increased to 2.2 x 10(9)/L (leucocyte count to 6.5 x 10(9)/L) after 24 hours. The second case was a 37-year-old man and was using mycophenolic acid, tacrolimus, and valacyclovir. Laboratory investigations revealed his leukocyte count to be 1.3 x 10(9)/L. Mycophenolic acid and valganciclovir were stopped owing to neutropenia. The patient was administered granulocyte colony-stimulating factor, and the neutrophil count increased to 3.8 x 10(9)/L (leucocyte count to 5.8 x 10(9)/L). The kidney functions did not deteriorate in either patient, and the patients' kidney functions were similar to baseline levels 12 months after surgery.. We conclude that granulocyte colony-stimulating factor can be used safely and effectively in renal transplant patients.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Cytomegalovirus Infections; Filgrastim; Ganciclovir; Granulocyte Colony-Stimulating Factor; Humans; Kidney Transplantation; Male; Neutropenia; Recombinant Proteins; Treatment Outcome; Valacyclovir; Valganciclovir; Valine

Topics: Acyclovir; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Agents; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Valacyclovir; Valganciclovir; Valine

To investigate clinical manifestations and response to antiviral therapy of 8 patients with cytomegalovirus (CMV)-induced corneal endotheliitis who were diagnosed and treated at 2 university hospitals in Japan.. Retrospective, consecutive, multicenter case series.. Eight eyes of 8 patients diagnosed with active CMV corneal endotheliitis at Kyoto Prefectural University of Medicine and Ehime University School of Medicine. The diagnosis was made based on the detection by polymerase chain reaction assay of CMV, but not herpes simplex virus (HSV) and varicella zoster virus (VZV) DNA, in the aqueous humor from the affected eye.. Retrospective review of the clinical manifestations and responses to antiviral treatment.. Patient profiles, including duration of corneal endotheliitis, systemic disease, intraocular pressure, and clinical manifestation of anterior and posterior segments. The clinical response to systemic and topical antiviral treatment was evaluated by slit-lamp examination. Corneal endothelial density was examined by specular microscopy.. The average observation period after CMV detection was 10.4 months (range, 2-24 months). None of the patients had systemic immunodeficiency. Corneal manifestations included linear keratic precipitates associated with multiple coin-shaped lesions and local corneal stromal edema. Of the 8 patients, 4 had undergone penetrating corneal transplantation. Systemic ganciclovir therapy was used in 7 patients, and in 1 patient, valacyclovir was administered, with the corneal endotheliitis responding quickly to the early administration of galovir. At the final examination, 6 eyes had a clear cornea, but 2 eyes had bullous keratopathy.. Besides HSV and VZV, CMV must be considered as an etiologic agent in patients with corneal endotheliitis. Cytomegalovirus corneal endotheliitis may be a newly identified clinical entity of reactivated CMV in the anterior chamber of individuals free of accompanying systemic symptoms.

Topics: Acyclovir; Administration, Topical; Aged; Aged, 80 and over; Antiviral Agents; Aqueous Humor; Cell Count; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Endothelium, Corneal; Eye Infections, Viral; Female; Ganciclovir; Humans; Keratitis; Male; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Valacyclovir; Valine

To report early experience with treatment of intrauterine cytomegalovirus (CMV) infection using maternal oral administration of valaciclovir (VACV).. Observational study of fetuses infected with CMV with or without treatment with valaciclovir.. Pregnancies with confirmed fetal CMV infection were treated with oral VACV (8 g/day).. Fetal viral load and drug concentration were monitored in amniotic fluid and in fetal blood. Data on the course and outcome of a group of untreated symptomatic fetuses infected with CMV are also reported.. Therapeutic concentrations were achieved in maternal and fetal bloods. The viral load in the fetal blood (VLFB) decreased significantly after 1-12 weeks of treatment (Wilcoxon paired test P = 0.02). Twenty pregnancies including 21 fetuses were treated at 28 weeks (median, range: 22-34) for 7 weeks (median, range: 1-12). Ten infants were developing normally at between 1 and 5 years of age. Two infants (both aged 2 years) had severe isolated unilateral deafness. One neonate presented with microcephaly and severe deafness but was also diagnosed with incontinentia pigmenti. Six out of seven cases that eventually required termination of pregnancy (TOP) had evidence of in utero progression of the disease with worsening cerebral lesions. One fetus died in utero. The outcome of 14/24 (58.3%) untreated symptomatic infected fetuses was poor with either TOP, intrauterine fetal demise or severe congenital infection disease of the neonate; the remaining ten infants were healthy at follow up.. Maternal oral administration of VACV leads to therapeutic concentrations in the maternal and fetal compartments, with a decrease in VLFB. Our results suggest that in cases where TOP is declined, a randomised controlled trial to study this treatment option further is indicated.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Cytomegalovirus Infections; DNA, Viral; Female; Fetal Blood; Fetal Diseases; Humans; Pilot Projects; Platelet Count; Pregnancy; Pregnancy Complications, Infectious; Self Administration; Valacyclovir; Valine; Viral Load

Valaciclovir (VACV) has been reported to induce adverse neuropsychiatric effects (ANE), especially in patients with renal failure, but few data are available for renal transplant recipients (RTR).. We conducted a retrospective study in RTR given VACV as cytomegalovirus prophylaxis, from January 1999 to December 2000, to define the incidence rate, type and outcome of VACV-induced ANE, and to identify risk factors for ANE. The VACV-induced ANE were defined as neuropsychiatric disorders justifying VACV dose reduction or withdrawal. Patients with and without VACV-induced ANE were compared by univariate and multivariate analysis.. In all, 167 RTR were included, of whom 25 (15%) displayed VACV-induced ANE (mainly hallucinations and confusion), which occurred with a mean of 4 days after the start of VACV. ANE were reversible in all cases. Multivariate analysis showed that delayed graft function (DGF) was the main risk factor for VACV-induced ANE [Odds ratio (OR): 12.1; 95% CI = 3.4-43.4; P = 0.0001]. All VACV doses given to patients with ANE were in accordance with the current recommended adaptation to estimated glomerular filtration rate (GFR).. In RTR, VACV-induced ANE are significantly frequent but reversible. DGF occurrence is the main risk factor for these ANE. In RTR with DGF, the recommended doses for GFR below 10 ml/min might be too high. Several strategies, in RTR with DGF, might lower the risk of ANE, including reduction of the currently recommended VACV dosage, delayed VACV introduction until improvement of renal function, or use of another anti-cytomegalovirus drug.

Topics: Acyclovir; Adult; Age Distribution; Analysis of Variance; Behavioral Symptoms; Cohort Studies; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; France; Graft Rejection; Humans; Incidence; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Neuropsychological Tests; Probability; Prognosis; Retrospective Studies; Risk Assessment; Sex Distribution; Valacyclovir; Valine

Ganciclovir and its prodrug, valganciclovir, are more effective than acyclovir in preventing cytomegalovirus (CMV) infection and disease in solid-organ transplant recipients. However, the indirect effects of prophylactic use of ganciclovir and acyclovir are comparable, and the greater effectiveness of ganciclovir may be compensated for by less drug-related toxicity with acyclovir or valacyclovir. No conclusive data exist concerning the best technique and duration of surveillance for CMV infection in patients for whom active surveillance for late-onset CMV should be performed, i.e., those reaching the end of prophylaxis. Only large randomised controlled trials, with long follow-up periods, will provide definitive conclusions regarding the comparative prophylactic roles of the major antiviral agents in this population, and how their use fits with a strategy of active surveillance and pre-emptive therapy.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Organ Transplantation; Valacyclovir; Valganciclovir; Valine

Prophylaxis-based antiviral treatment and intensive monitoring followed by pre-emptive antiviral treatment are both commonly used management strategies to reduce risk of cytomegalovirus (CMV) infection following renal transplantation. This study employed a decision-model approach using published efficacy data and information from a recent survey of French clinical practice to consider the relative costs and outcomes associated with CMV prevention strategies for high-risk patient groups. The cost per case of treating tissue invasive and symptomatic CMV disease was estimated at euro 15,431 and euro 10,852, respectively. In the highest infection-risk patient group (positive donor with no previous CMV history) prophylactic oral valaciclovir was shown to avoid the greatest number of CMV disease cases (35 cases per 100 transplanted patients) and reduced the overall CMV-related costs per transplanted patient by around 14% over a'wait-and-treat' baseline strategy. In contrast, intensive monitoring and preemptive treatment resulted in a much higher cost per transplanted patient. This analysis suggests that prophylactic treatment remains the most cost-effective approach to the management of CMV in renal-transplanted patients. Further comparative studies between prophylactic and pre-emptive treatment would be a valuable addition to the current evidence based on CMV prevention.

Topics: Acyclovir; Antiviral Agents; Cost-Benefit Analysis; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunocompromised Host; Kidney Transplantation; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Drug Resistance, Viral; Famciclovir; Guanine; Hepatitis B; Hepatitis C; Herpes Simplex; Herpes Zoster; Humans; Influenza, Human; Valacyclovir; Valine; Virus Diseases

We describe the emergence of a new ganciclovir resistance mutation in the UL97 gene of human cytomegalovirus, deletion of codon 601, after valaciclovir and short-term ganciclovir therapy following kidney transplantation. Its role in ganciclovir resistance was supported by decreased ganciclovir phosphorylation in a recombinant vaccinia virus system.

Topics: Acyclovir; Adolescent; Antiviral Agents; Chemoprevention; Codon; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Viral; Ganciclovir; Humans; Kidney Transplantation; Molecular Sequence Data; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor); Sequence Deletion; Valacyclovir; Valine

Despite increasing intensity and profound immunosuppression associated with newer therapies for hematologic malignancies, little information exists regarding cytomegalovirus (CMV) reactivation in settings other than allogeneic stem cell transplantation (SCT).. We reviewed the epidemiology of CMV disease in patients who were CMV polymerase chain reaction (PCR) positive during treatment for hematologic malignancies without allogeneic SCT from June 1999 to June 2004.. Thirty-six patients with CMV reactivation were identified. Of these, 92% were undergoing investigation for fever. Fifteen patients with CMV DNAemia were treated with ganciclovir without CMV disease developing. Notably, 20 patients with untreated CMV DNAemia did not develop CMV disease during a median follow-up of 3.5 (1-19) months. The highest rates of reactivation were observed with HyperCVAD (7.8%) and alemtuzumab (50%).. We recommend that screening for CMV DNAemia be instituted and pre-emptive therapy contemplated for asymptomatic CMV reactivation only in patients receiving alemtuzumab therapy, but not routinely for other patients outside the allogeneic SCT setting. Indeed for such patients, detection of isolated CMV DNAemia does not imply the need for immediate therapy and future studies are needed to validate PCR detection of CMV DNA and CMV DNA titers as predictors for CMV disease.

Topics: Acyclovir; Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Cohort Studies; Cyclophosphamide; Cytomegalovirus; Cytomegalovirus Infections; Dexamethasone; Diphtheria Toxin; DNA, Viral; Doxorubicin; Female; Fever; Follow-Up Studies; Ganciclovir; Hematologic Neoplasms; Humans; Interleukin-2; Male; Middle Aged; Peripheral Blood Stem Cell Transplantation; Polymerase Chain Reaction; Recombinant Fusion Proteins; Retrospective Studies; Rituximab; Transplantation, Autologous; Valacyclovir; Valine; Vidarabine; Vincristine; Viremia; Virus Activation

This analysis evaluates the cost-effectiveness of valaciclovir prophylaxis using clinically and economically important health outcomes including graft failure, life-years, and quality-adjusted life-years (QALYs).. A Markov model was developed using a randomized, placebo-controlled trial of valaciclovir prophylaxis, together with a published epidemiological study and national renal transplant registry data. The model's population was stratified into two risk groups by donor/recipient cytomegalovirus (CMV) serostatus at transplantation: donor-positive/recipient-negative (D+R-) and recipient-positive (R+) patients. The model estimated costs and health outcomes over a 30-yr period from the perspective of Australian health care providers.. The total health care cost was $3619 lower for D+R- patients receiving valaciclovir prophylaxis compared with those not receiving prophylaxis. D+R- patients receiving valaciclovir gained an extra 0.33 yr of life and 0.27 QALYs. R+ patients receiving valaciclovir prophylaxis gained an extra 0.07 yr of life and 0.05 QALYs, with an incremental cost of $914. This equates to $17 127 per QALY gained, which is highly cost-effective compared with other drugs and health interventions.. Valaciclovir for the prophylaxis of CMV disease in renal transplant recipients is a cost-effective intervention, significantly reducing the burden of CMV disease to patients and health care providers.

Topics: Acyclovir; Antiviral Agents; Chemoprevention; Cost-Benefit Analysis; Cytomegalovirus Infections; Graft Survival; Humans; Kidney Transplantation; Markov Chains; Models, Biological; Models, Economic; Quality of Life; Survival Analysis; Treatment Outcome; Valacyclovir; Valine

Whether valaciclovir (VCV) prophylaxis could be responsible for ganciclovir (GCV)-resistance of Human cytomegalovirus (HCMV) in transplantation has never been documented. A multicentric retrospective pilot study was undertaken to detect GCV-resistance through mutations within the UL97 gene in renal transplant recipients who experienced active HCMV infection and received valacyclovir prophylaxis. Twenty-three patients who experienced HCMV antigenaemia or DNAemia during or at the end of prophylaxis were included. UL97 genotyping was carried out on peripheral blood samples, using a nested in-house PCR, which amplified the full-length UL97 gene. One patient has a resistance-related mutation (M460I); the major risk factor for emergence of resistance in this patient was the presence of early and persistent antigenaemia. GCV-resistance during VCV-prophylaxis was rare after renal transplantation. However, special attention must be paid to patients developing early active HCMV infection under prophylaxis.

Topics: Acyclovir; Amino Acid Substitution; Antiviral Agents; Chemoprevention; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Viral; Female; Ganciclovir; Humans; Kidney Transplantation; Middle Aged; Phosphoproteins; Phosphotransferases (Alcohol Group Acceptor); Pilot Projects; Retrospective Studies; Valacyclovir; Valine; Viral Matrix Proteins

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Erythrocyte Indices; Erythrocytes, Abnormal; Female; Humans; Kidney Transplantation; Male; Middle Aged; Valacyclovir; Valine

Cytomegalovirus (CMV) is a major pathogen in renal transplant patients causing significant post-transplant morbidity and mortality. Prophylactic antiviral therapy, currently implemented in most kidney transplant centres, has significantly reduced the incidence of CMV infection after transplantation. Oral ganciclovir has been shown to be an effective prophylactic agent in preventing CMV disease and infection with a demonstrated superior efficacy over oral acyclovir. Valacyclovir, a prodrug of acyclovir with a higher level of bioavailability than acyclovir, has also been shown to be effective in preventing CMV disease when given as prophylactic treatment.. In a retrospective analysis of 150 renal transplant recipients in our centre, we compared the efficacy of oral ganciclovir with valacyclovir in preventing CMV infection. Seventy-seven consecutive renal transplant recipients prophylactically treated with oral ganciclovir for 12 weeks after transplant were compared with 73 consecutive recipients treated with oral valacylovir for an equal length of time.. No difference was noted in the incidence of CMV infection between the two treatment groups (5.1 vs 5.4%) after a 6 month follow-up. Likewise, the incidence of acute rejection was similar in both groups (11.6 vs 6.8%). All cases of CMV infection occurred in high-risk patients (donor positive/recipient negative).. The prophylactic use of oral valacylovir is as effective as oral ganciclovir in reducing CMV infection and disease after kidney transplantation.

Topics: Acyclovir; Administration, Oral; Adult; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Ganciclovir; Graft Rejection; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Preoperative Care; Probability; Retrospective Studies; Risk Assessment; Treatment Outcome; Valacyclovir; Valine

Mycophenolate mofetil (MMF) is a drug which decreases the frequency of renal transplantation rejection. However, cytomegalovirus infections are a common feature of this treatment leading the physicians to prescribe antiviral prophylactic drugs like valacyclovir. During this association, neutropenia occur and the cause of this adverse effect is difficult to define. This report presents a case of neutropenia in a woman treated with MMF and valacyclovir. As the duration of the valacyclovir treatment exactly corresponds to the neutropenia duration, and the mycophenolate trough levels increased with the neutrophil count, the responsibility of this neutropenia was ascribed to valacyclovir. However, an examination of the literature for cases of neutropenia led to the suspicion of an interaction between MMF and valacyclovir. Mycophenolate may increase intracellular concentrations of valacyclovir up to haematotoxic levels. This mechanism may explain the interaction and further research is needed to confirm this interaction.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Drug Interactions; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Neutropenia; Valacyclovir; Valine

High-dose valaciclovir at up to 8 g/day has been shown to be effective in prophylaxis against cytomegalovirus (CMV) disease in renal transplant recipients. We report our experience with low-dose valaciclovir prophylaxis of up to 3 g/day, adjusted to creatinine clearance. A group of patients at high risk of developing CMV disease who received prophylaxis were selected as the study group. This included all CMV-positive patients who received antilymphocyte therapy (R+, n=20) and all CMV-negative recipients of CMV-positive organs (D+R-, n=15). D+R- patients receiving antilymphocyte therapy were excluded, as most of the patients in the control group had received ganciclovir prophylaxis. A historical control group was used, which consisted of patients who did not receive prophylaxis. Low-dose valaciclovir prophylaxis resulted in a statistically significant decrease (8.5 vs 37%, P=0.004) in CMV disease in the study group at 6 months. On subgroup analysis the decrease was statistically significant only in the R+ group (5 vs 45%, P=0.003), not in the D+R- group (13.3 vs 26.6%, P=0.651). Low-dose valaciclovir prophylaxis seems to be adequate for R+ patients receiving antilymphocyte therapy. The role of low-dose valaciclovir prophylaxis needs to be assessed further in a prospective trial.

Topics: Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Postoperative Complications; Prodrugs; Reoperation; Retrospective Studies; Tissue Donors; Valacyclovir; Valine

Routine cytomegalovirus (CMV)-pp65 antigenaemia monitoring shows that some patients will develop pp65 antigenaemia during valaciclovir prophylaxis or after cessation of treatment. The aim of this pilot study was to evaluate the safety and efficacy of lowering immunosuppression in kidney transplant recipients who exhibit mildly symptomatic CMV infections while on valaciclovir prophylaxis.. We selected 12 patients who experienced mildly symptomatic CMV infections defined as a positive CMV-pp65 antigenaemia test associated with either neutropenia, asthenia or arthralgia, but no fever. All of them received prophylaxis with valaciclovir for at least 3 months. Testing for CMV-pp65 antigenaemia was performed weekly for 6 months.. The mildly symptomatic infections occurred at a median interval of 69 days after transplantation-during prophylaxis in eight cases and after valaciclovir discontinuation in the other four cases. All of them were effectively managed by lowering immunosuppressive therapy, leading to the disappearance of symptoms and CMV antigenaemia reduction. No immunological complication or recurrence of CMV infection or disease was noted. I.v. ganciclovir never became necessary.. The mildly symptomatic CMV infections occurring in valaciclovir-treated patients may be managed efficiently and without immunologic complication by lowering immunosuppressive therapy.

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Cytomegalovirus Infections; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Pilot Projects; Valacyclovir; Valine

Prevention of cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT) generally involves preemptive treatment of recognized infection before the onset of overt CMV-associated disease. The success of this method depends on efficient recognition of infection and intervention before the disease progresses. Reliable tests for such diagnosis include blood culture, antigenemia assays, polymerase chain reaction assays, and other DNA sequence- or RNA sequence-based assays. For selected high-risk patients, such as patients receiving T cell-depleted hematopoietic stem cell transplants, prophylactic use of antiviral agents before the onset of CMV infection is recommended. The ability to monitor the immunological status of the patient relative to CMV-specific immunity is increasing in importance. Ultimately, the solution to the problem of efficient prevention of CMV infection in this population will require combined antiviral chemotherapy and improved reconstitution of CMV immunity.

Topics: Acyclovir; Antiviral Agents; Chemoprevention; Cidofovir; Cytomegalovirus; Cytomegalovirus Infections; Cytosine; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Organophosphonates; Organophosphorus Compounds; Postoperative Complications; Risk Factors; Transplantation, Autologous; Transplantation, Homologous; Valacyclovir; Valganciclovir; Valine

Topics: Acyclovir; Antigens, Viral; Antiviral Agents; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Prodrugs; Valacyclovir; Valine

A retrospective single center study was performed to evaluate the safety and efficacy of valacyclovir for prevention of cytomegalovirus (CMV) infection (reactivation) after allogeneic stem cell transplantation (SCT). We compared a group of 31 patients at risk for CMV reactivation (donor, recipient or both seropositive for CMV) who received valacyclovir at an oral dose of 1 g three times a day for CMV prophylaxis with a matched cohort of 31 patients who did not receive the drug or any other form of CMV prophylaxis. Valacyclovir was used as primary prophylaxis in 12 patients and as secondary prophylaxis (after a prior CMV reactivation was effectively treated with either ganciclovir or foscarnet and without CMV antigenemia at the start of valacyclovir) in the remaining 19 patients. The two treatment groups were well matched for the donor-recipient CMV serological status and other pre-transplant characteristics. CMV reactivation was detected by blood antigenemia testing using a commercially available immunofluorescence assay for CMV lower matrix protein pp65 in circulating leukocytes. For primary prophylaxis, 3/12 patients who received valacyclovir reactivated CMV compared to 24/31 patients in the control group (P < 0.001). For secondary prophylaxis, 5/19 valacyclovir patients reactivated compared to 16/24 control patients (P < 0.05). Valacyclovir was well tolerated except for infrequent and mild gastrointestinal side-effects. There was no difference in the incidence of CMV disease in the two groups. Prophylaxis with valacyclovir appears to be safe and efficacious in preventing both primary and secondary CMV reactivation in at-risk patients after allogeneic SCT. Larger prospective randomized studies will be required to confirm these observations.

Topics: Acyclovir; Adult; Antiviral Agents; Cohort Studies; Consumer Product Safety; Cytomegalovirus Infections; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Phosphoproteins; Retrospective Studies; Therapeutic Equivalency; Transplantation, Homologous; Valacyclovir; Valine; Viral Matrix Proteins; Virus Activation

Valaciclovir (VACV) 2 g q.i.d. for 3 months after kidney transplantation has been shown, (Lowance et al., NEJM 1999; 340: 1462-70), to reduce CMV disease from 45 to 16% and rejection from 52 to 26% in CMV-negative (D+R-) recipients. Neurotoxic side effects, however, were frequent, and 5% of the patients experienced hallucinations. We hypothesised that a lower dosage of VACV would prevent CMV disease with fewer CNS side effects.. Since September 1998 all CMV-mismatched renal transplant recipients received VACV 1 g t.i.d. for 3 months posttransplantation (PT). The incidence of CMV disease, rejection and neurotoxic side effects during 6 months PT was studied retrospectively in, up to now, 25 patients.. 24% (6/25) of the patients developed CMV disease. The mean time for onset of symptoms was 145 days (92-191). Five of the patients had mild-moderate symptoms and recovered after ganciclovir therapy for 3 weeks. One patient was diagnosed with a CMV-associated retinitis on day 191 PT. The rate of biopsy-confirmed acute graft rejection was 32% (8/25). 20% (5/25) of the patients had a serum creatinine of >200 micromol/l after 6 months, including one patient on hemodialysis. CNS adverse effects were not observed. None out of nine patients with basiliximab induction and VACV developed CMV disease. One patient with basiliximab that did not receive VACV, developed a symptomatic CMV-infection.. The incidence of CMV disease was lower than in historical controls at our centre, and the time to onset of symptoms was prolonged. Compared to the 8 g VACV/day study, CMV disease and graft rejection was more frequent, but no neurotoxic side effects were observed. A combination with basiliximab induction and VACV 3 g/day shows promising results, but randomised studies are needed for confirmation.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Cytomegalovirus Infections; Female; Graft Survival; Humans; Incidence; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Female; Humans; Kidney Transplantation; Male; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Humans; Kidney; Kidney Transplantation; Postoperative Complications; Safety; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Microbial; Ganciclovir; Humans; Organ Transplantation; Postoperative Complications; Valacyclovir; Valine

Cytomegalovirus (CMV) disease may occur following renal transplantation and has been shown to have health and cost consequences in this setting.. To compare the cost effectiveness of different CMV management strategies for renal transplant patients: prophylaxis with (i) oral valaciclovir or (ii) intravenous ganciclovir; viral testing for CMV followed by (iii) pre-emptive therapy with intravenous ganciclovir or (iv) adjustment of immunosuppression and intensive monitoring; or (v) waiting to treat when CMV disease develops.. A decision-tree model was constructed that included the different management strategies for the donor seropositive/recipient seronegative (D+R-) population. Clinical outcomes for the D+R- population came from clinical trials. Treatment algorithms and costs for CMV syndrome and tissue invasive disease were developed from published literature and UK physician interviews. One- and 2-way sensitivity analyses were performed.. UK National Health Service.. Prophylaxis with either oral valaciclovir or intravenous ganciclovir dominated (lower costs and fewer cases of CMV disease) the pre-emptive treatment and wait-and-treat strategies. The cost per patient was from 157 Pounds to 438 Pounds higher with oral valaciclovir prophylaxis compared with intravenous ganciclovir prophylaxis and the incremental cost per case of CMV disease avoided with valaciclovir prophylaxis ranged from 2243 Pounds to 8111 Pounds (1996 values). These results are sensitive to the efficacy of intravenous ganciclovir prophylaxis and CMV management costs.. For D+R- renal transplant patients, prophylaxis is the dominant (more effective and less costly) management strategy compared with pre-emptive and wait-and-treat strategies. The cost per patient with oral valaciclovir prophylaxis compared with intravenous ganciclovir prophylaxis is slightly higher in our base case scenario, but may be lower under reasonable alternative assumptions.

Topics: Acyclovir; Administration, Oral; Algorithms; Antiviral Agents; Cost-Benefit Analysis; Cytomegalovirus Infections; Decision Trees; Drug Costs; Ganciclovir; Humans; Injections, Intravenous; Kidney Transplantation; Postoperative Complications; Premedication; Valacyclovir; Valine; Virus Shedding

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Cytomegalovirus Infections; Female; Humans; Kidney Transplantation; Middle Aged; Postoperative Complications; Valacyclovir; Valine

Results of a study of high-dosage (8 g/day) valaciclovir and its relation to cytomegalovirus (CMV) disease show that 15 percent of subjects developed complications of CMV disease. Although some subjects developed CMV disease (12 percent) during valaciclovir treatment, the study reveals that there was an overall 33 percent reduction in the development of CMV in people using the drug. Gastrointestinal complaints occurred more often and earlier with subjects using valaciclovir rather than acyclovir. Also, signs of thrombotic microangiopathy occurred significantly more often in valaciclovir users versus acyclovir users. Reduced survival rates compared to acyclovir were noted, although this could be a result of too high of a dose of valaciclovir being administered.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Humans; Male; Valacyclovir; Valine

In persons with AIDS (PWAs), cytomegalovirus (CMV) infection can cause a broad spectrum of clinical manifestations. The most common clinical manifestations associated with CMV infection in PWAs and the most current approaches to treatment and prevention of CMV disease are reviewed. Manifestations discussed include those involving ocular disease, and diseases of the gastrointestinal and central nervous systems. Prophylactic treatment for CMV disease includes the use of oral ganciclovir and valaciclovir. Concluding comments address the development of antiviral resistance by CMV. Tables include listings of potential strategies for use of oral ganciclovir prophylaxis in PWAs, and mechanisms by which CMV strains become resistant to ganciclovir, foscarnet, and cidofovir.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Central Nervous System Diseases; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Digestive System Diseases; Foscarnet; Ganciclovir; Humans; Valacyclovir; Valine

Studies reveal that using PCR to measure CMV viral load is a promising source of information on the prophylactic value of using oral ganciclovir and valaciclovir. One study showed the greatest effect of valaciclovir treatment in patients who were PCR viremic at baseline. This shows a preemptive effect in aborting the development of CMV disease. Another study demonstrated that CMV PCR could be used prospectively to follow patients with constitutional symptoms and low CD4 counts (less than 50) in order to detect early development of asymptomatic CMV retinitis. The continued refinement of this technology and its ultimate commercial availability promise to revolutionize the management of CMV disease in advanced stage HIV infection.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; HIV Infections; Humans; Polymerase Chain Reaction; Prospective Studies; Valacyclovir; Valine; Viral Load; Viremia

As more drugs are approved for the prevention of opportunistic infections, concerns regarding the benefits and potential risks of these therapies are arising. A synopsis of the data for prophylaxis against opportunistic infections is provided for the following: Pneumocystis carinii pneumonia, fungal infections, Mycobacterium avium complex, cytomegalovirus infections, and toxoplasmosis. General precautions in using preventive medications for people with fewer than 100 CD4 plus cells are highlighted.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Clarithromycin; Clindamycin; Clinical Trials as Topic; Clotrimazole; Cytomegalovirus Infections; Dapsone; Fluconazole; Ganciclovir; Humans; Itraconazole; Leucovorin; Mycobacterium avium-intracellulare Infection; Mycoses; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Valacyclovir; Valine

NIAID's AIDS Clinical Trials Group (ACTG) has completed several studies and their findings are reported. Findings from two studies, ACTG 081, involving three therapies for pneumonia prevention, and ACTG 981, examining fluconazole for preventing fungal infections, are reported in The New England Journal of Medicine (March 16, 1995). Other studies reviewed include ACTG 152, using AZT alone and in combination in children, and ACTG 204, examining the effectiveness of valacyclovir and two different doses of acyclovir in preventing cytomegalovirus end stage-organ disease and survival extension.

Topics: Acyclovir; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Didanosine; Drug Therapy, Combination; Fluconazole; HIV Infections; Humans; Mycoses; Pneumonia, Pneumocystis; Valacyclovir; Valine; Zidovudine