acyclovir and Viremia

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Pre-emptive treatment of patients with CMV viraemia using antiviral agents has been suggested as an alternative to routine prophylaxis to prevent CMV disease. This is an update of a Cochrane review first published in 2005.. This review was conducted to evaluate the efficacy of pre-emptive treatment with antiviral medications in preventing symptomatic CMV disease.. For this update, we searched the Cochrane Renal Group's Specialised Register (to 16 January 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review.. We included randomised controlled trials (RCTs) of pre-emptive treatment compared with placebo, no specific treatment or with antiviral prophylaxis in solid organ transplant recipients.. Four authors assessed the quality and extracted all data. Analyses used a random-effects model and results were expressed as risk ratio (RR) and 95% confidence intervals (CI).. We identified 15 eligible studies (1098 participants). Of these, six investigated pre-emptive treatment versus placebo or treatment of CMV when disease occurred (standard care), eight looked at pre-emptive treatment versus antiviral prophylaxis, and one reported on oral versus intravenous pre-emptive treatment.Assessment of risk of bias identified that the processes reported for sequence generation and allocation concealment were at low risk of bias in only five and three studies, respectively. All studies were considered to be at low risk of attrition bias, and seven studies were considered to be at low risk of bias for selective reporting. Only one study reported adequate blinding of participants and personnel; no study reported blinding of outcome assessment.Compared with placebo or standard care, pre-emptive treatment significantly reduced the risk of CMV disease (6 studies, 288 participants: RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (3 studies, 185 participants: RR 1.21, 95% CI 0.69 to 2.12) or all-cause mortality (3 studies, 176 participants: RR 1.23, 95% CI 0.35 to 4.30). Comparative studies of pre-emptive therapy versus prophylaxis showed no significant differences in preventing CMV disease between pre-emptive and prophylactic therapy (7 studies, 753 participants: RR 1.00, 95% CI 0.36 to 2.74) but there was significant heterogeneity (I² = 63%). Leucopenia was significantly less common with pre-emptive therapy compared with prophylaxis (6 studies, 729 participants: RR 0.42, 95% CI 0.20 to 0.90). Other adverse effects did not differ significantly or were not reported. There were no significant differences in the risks of all-cause mortality, graft loss, acute rejection and infections other than CMV.. Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care. Despite the inclusion of five additional studies in this update, the efficacy of pre-emptive therapy compared with prophylaxis to prevent CMV disease remains unclear due to significant heterogeneity between studies. Additional head-to-head studies are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunocompromised Host; Opportunistic Infections; Organ Transplantation; Randomized Controlled Trials as Topic; Viremia

Viral encephalitis causes an altered level of consciousness, which may be associated with fever, seizures, focal deficits, CSF pleocytosis, and abnormal neuroimaging. Potential pathogens include HSV, VZV, enterovirus, and in some regions, arboviruses. Autoimmune (eg, anti-NMDA receptor) and paraneoplastic encephalitis are responsible for some cases where no pathogen is identified. Indications for ICU admission include coma, status epilepticus and respiratory failure. Timely initiation of anti-viral therapy is crucial while relevant molecular and serological test results are being performed. Supportive care should be directed at the prevention and treatment of cerebral edema and other physiological derangements which may contribute to secondary neurological injury.

Topics: Acyclovir; Adrenal Cortex Hormones; Anticonvulsants; Antiviral Agents; Brain Diseases; Brain Edema; Consciousness Disorders; Encephalitis; Encephalitis, Viral; Encephalomyelitis, Acute Disseminated; Glasgow Coma Scale; Guillain-Barre Syndrome; Hashimoto Disease; Humans; Intensive Care Units; Paraneoplastic Syndromes, Nervous System; Seizures; Status Epilepticus; Viremia

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Pre-emptive treatment with antiviral agents of patients with CMV viraemia has been widely adopted as an alternative to routine prophylaxis to prevent CMV disease.. This review was conducted to evaluate the efficacy of pre-emptive treatment in preventing symptomatic CMV disease.. The Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library Issue 2, 2005), MEDLINE (1966 to February 2005), EMBASE (1980 to February 2005) and reference lists and conference proceedings were searched.. We included randomised controlled trials (RCTs) of pre-emptive treatment versus placebo, no treatment or antiviral prophylaxis in solid organ transplant recipients.. Two authors assessed the quality and extracted all data. Analysis was with a random-effects model and results expressed as relative risk (RR) and 95% confidence intervals (CI).. Ten eligible trials (476 patients) were identified, six of pre-emptive treatment versus placebo or treatment of CMV when disease occurred (standard care), three of pre-emptive treatment versus antiviral prophylaxis and one of oral versus intravenous pre-emptive treatment. Compared with placebo or standard care, pre-emptive treatment significantly reduced the risk of CMV disease (six trials, 288 patients: RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (three trials, 185 patient: RR 1.06, 95% CI 0.64 to 1.76) or all-cause mortality (two trials, 176 patients: RR 1.23, 95% CI 0.35 to 4.30). Comparative trials of pre-emptive therapy versus prophylaxis showed no significant difference in the risks of CMV disease, acute rejection or all-cause mortality.. Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care, but additional head-to-head trials are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunocompromised Host; Opportunistic Infections; Organ Transplantation; Randomized Controlled Trials as Topic; Viremia

In contrast to the frequent occurrence of localized herpes simplex virus (HSV) infections during pregnancy, disseminated disease has rarely been reported.. A 21-year-old woman in the 27th week of gestation developed a catastrophic illness characterized by fever, progressive pneumonia, respiratory failure, leukopenia, disseminated intravascular coagulation (DIC), anicteric hepatitis, septic shock and acute renal failure. Initial studies for an infectious etiology were negative. In spite of empiric broad-spectrum antimicrobial therapy, her condition continued to deteriorate. Sparse vesicular skin lesions suggestive of HSV infection subsequently appeared. Despite initiation of acyclovir therapy, the patient died. HSV type 2 was cultured from a skin vesicle, and at autopsy there was extensive necrosis of the liver and lung with immunohistochemical stains positive for HSV antigen.. In the third trimester of pregnancy, HSV can occasionally disseminate in immunocompetent women. A clinical syndrome of unexplained fever, pneumonia, anicteric hepatitis, leukopenia and DIC without mucocutaneous lesions should prompt investigation and possible treatment for disseminated HSV infection.

Topics: Acyclovir; Adult; Antigens, Viral; Antiviral Agents; Diagnosis, Differential; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunohistochemistry; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Third; Viremia

Human cytomegalovirus (HCMV) infection and disease remain a major cause of morbidity and mortality after bone marrow transplantation. HCMV disease, especially pneumonitis, may be treated with ganciclovir and immunoglobulin but even so the outcome is poor with mortality rates of 30-70%. It is therefore imperative to treat HCMV infection before it develops into disease. The aim of this article is to describe the main strategies used to prevent HCMV infection and to improve the survival after CMV disease in bone marrow transplant recipients.. In the present review, we examined personal papers in this field and articles published in journals covered by the Science Citation Index and Medline.. Major advances have been made in preventing HCMV infection and disease through two different approaches, both of which reduce HCMV induced morbidity and mortality: In pre-emptive therapy, patients are given ganciclovir when HCMV infection is first identified and this is continued 3-4 months after transplantation; in prophylactic therapy ganciclovir is given to all patients at risk of HCMV disease from engraftment up to 3-4 months post transplantation. Each strategy has advantages and disadvantages and there is no evidence for the superiority of one over the other since the overall survival is the same and the incidence of death from HCMV disease is similar.. The use of more sensitive tests such as HCMV PCR or antigenemia may improve the outcome but probably will not eradicate all HCMV disease. Future possible strategies could include adoptive transfer of CD8+ HCMV-specific cytotoxic T lymphocytes clones derived from the donor marrow or boosting donor or patient immunity using subunit anti-HCMV vaccines such as gB or pp65.

Topics: Acyclovir; Adolescent; Adult; Antigens, Viral; Antiviral Agents; Bone Marrow Transplantation; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Hematopoietic Stem Cells; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunotherapy, Adoptive; Infant; Pneumonia, Viral; Risk Factors; Sensitivity and Specificity; T-Lymphocytes, Cytotoxic; Transplantation Conditioning; Transplantation, Homologous; Viral Vaccines; Viremia; Virus Activation

Topics: Acyclovir; Antiviral Agents; Bone Marrow Transplantation; Cytomegalovirus Infections; Ganciclovir; Heart Transplantation; Humans; Liver Transplantation; Monitoring, Physiologic; Organ Transplantation; Risk Factors; Viral Load; Viremia

Herpes simplex virus may cause serious infections in neonates. In case of foetal infection in the first trimenon, abortions, stillbirth, prematurity, intrauterine growth retardation (not obligatory) and various malformations may result. Neonatal HSV infection is mostly the consequence of intrapartum virus acquisition during passage through the birth canal. The infection is mostly localised on the skin, at the eyes or the mouth or disseminated with or without HSV meningoencephalitis. It is difficult to establish the diagnosis, because neonatal herpes disease in the early stage is not easy to distinguish from other diseases in the newborn such as RDS, NEC or ICH. Antiviral therapy with aciclovir is the treatment of choice and seems to improve the outcome of neonatal herpes. Prognosis depends on early therapy. Treatment should be initiated in relation to clinical findings, because available diagnostic techniques do not always permit an early detection of the disease.

Topics: Acyclovir; Diagnosis, Differential; Female; Herpes Simplex; Humans; Infant, Newborn; Pneumonia, Viral; Pregnancy; Viremia

OBJECTIVE To determine whether prophylactic administration of valacyclovir hydrochloride versus initiation of treatment at the onset of fever would differentially protect horses from viral replication and clinical disease attributable to equine herpesvirus type-1 (EHV-1) infection. ANIMALS 18 aged mares. PROCEDURES Horses were randomly assigned to receive an oral placebo (control), treatment at detection of fever, or prophylactic treatment (initiated 1 day prior to viral challenge) and then inoculated intranasally with a neuropathogenic strain of EHV-1. Placebo or valacyclovir was administered orally for 7 or 14 days after EHV-1 inoculation or detection of fever (3 horses/group). Effects of treatment on viral replication and clinical disease were evaluated. Plasma acyclovir concentrations and viremia were assessed to determine inhibitory concentrations of valacyclovir. RESULTS Valacyclovir administration decreased shedding of virus and viremia, compared with findings for control horses. Rectal temperatures and clinical disease scores in horses that received valacyclovir prophylactically for 2 weeks were lower than those in control horses. The severity of but not the risk for ataxia was decreased by valacyclovir administration. Viremia was decreased when steady-state trough plasma acyclovir concentrations were > 0.8 μg/mL, supporting the time-dependent activity of acyclovir. CONCLUSIONS AND CLINICAL RELEVANCE Valacyclovir treatment significantly decreased viral replication and signs of disease in EHV-1-infected horses; effects were greatest when treatment was initiated before viral inoculation, but treatment was also effective when initiated as late as 2 days after inoculation. During an outbreak of equine herpesvirus myeloencephalopathy, antiviral treatment may be initiated in horses at various stages of infection, including horses that have not yet developed signs of viral disease.

Topics: Acyclovir; Animals; Antiviral Agents; Female; Fever; Herpesviridae Infections; Herpesvirus 1, Equid; Horse Diseases; Horses; Premedication; Valacyclovir; Valine; Viremia; Virus Replication

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

A phase 2 trial was conducted to evaluate the efficacy of a topical antiviral, sorivudine, as an adjuvant to valacyclovir for the treatment of acute herpes zoster.. In this randomized, placebo-controlled, double-blind trial, 25 patients were treated with either sorivudine or placebo cream. All patients began 7 days of valacyclovir treatment on day 3. Zoster lesion swab samples and samples of peripheral blood mononuclear cells were collected periodically throughout the study and were analyzed for varicella-zoster virus (VZV) DNA by use of both qualitative and real-time polymerase chain reaction. Serum samples collected periodically throughout the study were analyzed for VZV DNA by use of real-time polymerase chain reaction.. VZV DNA was detected in all 3 sample types, and the number of viral copies correlated with the progression of herpes zoster. No statistically significant differences were seen between the placebo- and sorivudine-treated groups with respect to clinical characteristics or laboratory test results.. The detection of VZV DNA in the serum and peripheral blood mononuclear cells of all 25 zoster patients documents that viremia is a common manifestation of herpes zoster. Sorivudine cream appears to be a safe and well-tolerated adjuvant therapy; however, further phase 2 studies are needed to determine its clinical efficacy for the treatment of herpes zoster. Trials registration. ClinicalTrials.gov identifier: NCT00652184.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; DNA, Viral; Double-Blind Method; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Middle Aged; Patient Selection; Placebos; Valacyclovir; Valine; Viremia

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

To establish the incidence of CMV viremia after allogeneic blood stem cell transplantation, we studied 51 consecutive allogeneic peripheral blood stem cell (PBSC) transplant recipients. A total of 12 recipients were at moderate risk for CMV disease and 39 were at high risk. Conditioning regimens varied, but GvHD prophylaxis consisted of tacrolimus and mini-methotrexate in all patients. All patients received prophylactic ganciclovir from admission until day -2 and prophylactic acyclovir from day -1 until day 180 after transplantation. CMV viremia was treated with ganciclovir. Using a PCR-based technique, the cumulative incidence of CMV viremia was 31+/-14% by day 100 and 35+/-14% by day 150. Donor type, CMV risk group, underlying disorder, conditioning regimen, GvHD, and steroid use were not associated with the risk for CMV viremia. No cases of CMV disease occurred. We hypothesize that the low rate of CMV viremia and the absence of CMV disease in this cohort of PBSCT transplant recipients, which contrasts with other reports, may be related to the prophylactic use of high-dose acyclovir and possibly to pretransplant use of ganciclovir.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Incidence; Male; Middle Aged; Peripheral Blood Stem Cell Transplantation; Polymerase Chain Reaction; Premedication; Risk Factors; Transplantation, Homologous; Viremia

Cytomegalovirus (CMV) disease remains a major cause of morbidity following allogeneic stem cell transplantation (SCT). In a prospective randomized trial, we tested prophylactic therapy with ganciclovir or acyclovir for patients at high risk of disease. Ninety-one CMV seropositive recipients of related (n = 53) and unrelated (n = 38) donor transplants were enrolled. All patients received intravenous (i.v.) ganciclovir 5 mg/kg every 12 h days -7 to -2, followed by acyclovir 10 mg/kg i.v. every 8 h from day -1 until neutrophil engraftment. Patients were then randomly assigned to either ganciclovir (n = 45) or acyclovir (n = 46) until day 100 post transplant. Any degree of antigenemia was treated with ganciclovir 5 mg/kg i.v. twice a day for 2 weeks, followed by 5 mg/kg i.v. each weekday for 6 weeks. At day 100, the cumulative incidence of antigenemia was 31% (95% CI 17-45%) for ganciclovir and 41% (95% CI 26-56%) (P = 0.22) for acyclovir prophylaxis, respectively. The assigned prophylaxis cohort did not predict for CMV antigenemia. The cumulative incidence of CMV disease at 12 months was 13% (95% CI 3-23%) and 17% (95% CI 6-28%) (P = 0.59) for the ganciclovir- and acyclovir-treated groups, respectively. An absolute neutrophil count (ANC)

Topics: Acyclovir; Adolescent; Adult; Antigens, Viral; Bone Marrow Transplantation; Child; Child, Preschool; Cohort Studies; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Incidence; Infant; Life Tables; Male; Middle Aged; Minnesota; Neutropenia; Prospective Studies; Survival Analysis; Transplantation, Homologous; Treatment Outcome; Viremia; Virus Latency; Virus Replication

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

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

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). Our aim was to study the prophylactic effect of high-dose intravenous acyclovir given around the time of BMT followed by oral acyclovir on CMV infection and survival. 310 BMT recipients at risk of developing CMV infection were randomised to one of three regimens in a double-blind and double-dummy design: intravenous acylclovir (500 mg/m2, three times a day) for 1 month followed by oral acyclovir (800 mg four times a day for a further 6 months) (intravenous/oral group); intravenous acyclovir followed by oral placebo (intermediate group); or low-dose oral acyclovir (200 or 400 mg, four times a day) followed by placebo ("controls"). Analysis was by intention-to-treat. Intravenous acyclovir significantly reduced the probability of and delayed the onset of CMV infection. There was no further reduction in infection risk with the addition of long-term oral acyclovir. Time to CMV viraemia was delayed in the intravenous/oral acyclovir group compared with controls. Extending the prophylaxis with oral acyclovir significantly improved survival: 79 of 105 recipients were still alive at 7 months compared with 60 of 102 controls (p = 0.012). Although the intravenous/oral acyclovir group did significantly better than controls in terms of survival, the difference between the intravenous/oral acyclovir group and the intermediate group was of borderline statistical significance (p = 0.054). Adverse events that were possibly treatment related were similar in all three groups. The most commonly reported events were nausea, vomiting, elevated creatinine, and renal failure. High-dose intravenous followed by oral acyclovir improved survival and was of benefit in prophylaxis against the effects of CMV after BMT. Interpretation of CMV infection was made difficult because an intermediate treatment (intravenous acyclovir followed by oral placebo) was as effective as high-dose intravenous/oral acyclovir.

Topics: Acyclovir; Administration, Oral; Adult; Bone Marrow Transplantation; Cytomegalovirus Infections; Double-Blind Method; Female; Herpes Simplex; Humans; Injections, Intravenous; Longitudinal Studies; Male; Premedication; Survival Rate; Viremia

Cytomegalovirus disease is an important cause of morbidity following liver transplantation. To date there has not been an effective prophylaxis for CMV disease after liver transplantation. One hundred forty-three patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for 3 months after transplantation (acyclovir group) or intravenous ganciclovir (5 mg/kg twice a day) for 14 days followed by high dose oral acyclovir to complete a 3-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection compared with 16 of 68 (24%) from the ganciclovir group (relative risk, 3.69; 95% confidence interval, 2.07-6.56; P < 0.00001). Of those randomized, CMV disease was seen in 20 (28%) of the acyclovir group compared with 6 (9%) of the ganciclovir group (relative risk, 5.11; 95% confidence interval, 2.05-12.75; P = 0.0001). The median time to onset of CMV infection was 45 days in the acyclovir group compared with 78 days in the ganciclovir group (P = 0.004). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganciclovir patients (P = 0.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive disease and recurrent CMV disease were less frequent in the ganciclovir group. It is concluded that a course of 2 weeks of ganciclovir immediately after transplantation followed by high dose oral acyclovir for 10 weeks is superior to a 12-week course of high dose oral acyclovir alone for prevention of both CMV infection and CMV disease after liver transplantation. However, the lack of significant effect in seronegative recipients who received grafts from seropositive donors suggests that other strategies are needed to prevent CMV infection in this high risk population.

Topics: Acyclovir; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Ganciclovir; Humans; Incidence; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Prospective Studies; Recurrence; Risk Factors; Survival Rate; Viremia

Cytomegalovirus (CMV) infections, either primoinfection or reactivation, remain an important problem in organ transplantation. We therefore designed a prospective study in which pre-transplant CMV-positive renal transplant (RT) patients were randomized to receive for 3 months starting immediately after transplantation either acyclovir or nothing. Between April 1992 and January 1993, 53 cadaveric renal transplantations were performed in our institution. The immunosuppressive regimen included anti-thymoglobulins (ATG), azathioprine, steroids and cyclosporine A. Patients randomized in the acyclovir arm received the drug from day 1 to day 90 (D90) intravenously as long as the creatinine clearance was not above 10 ml/min and per os afterwards (3200 mg/day if the creatinine clearance was above 50 ml/min). CMV viraemia tests were systematically performed every 2 weeks until day 90 or when febrile episodes occurred. The patients were 53 adults who received a RT during the study period; 37 were included in the study of which 19 received acyclovir prophylaxis (group A) and 18, no prophylaxis (group B). The two groups did not significantly differ according to sex ratio, recipient's age, number of CMV-negative donors and number of days on ATG (10.76+/-6.16 vs. 8.28+/-4.21 days). There were significantly fewer viraemia episodes in group A (n = 6) than in group B (n = 13, P < 0.05); nevertheless, the percentage of symptomatic CMV viraemia was the same in both groups (35% vs. 38.5%). The onset of CMV viraemia occurred in the same period in both groups (39+/-13.8 days vs. 34.3+/-15 days; P = NS). The number of rejection episodes in the study period was the same in both groups (8 in each). We conclude from this prospective study that post-RT acyclovir prophylaxis reduces significantly the number of CMV viraemia episodes but does not delay their onset. Furthermore, it has no effect upon the percentage of symptomatic viraemias.

Topics: Acyclovir; Adult; Antiviral Agents; Creatinine; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Recurrence; Tissue Donors; Viremia

Ganciclovir susceptibility studies were done on the last cytomegalovirus (CMV) isolate available from 42 solid organ transplant recipients with CMV viremia who were enrolled in a prospective CMV prophylactic trial. Viruses were categorized as follows: 13 isolates (group 1) from patients who received ganciclovir prophylaxis; 9 isolates (group 2) from patients who received acyclovir prophylaxis; 8 isolates (group 3) from patients who received acyclovir prophylaxis and ganciclovir treatment; and 12 isolates (group 4) from patients who received prophylaxis and treatment with ganciclovir. All CMV isolates were sensitive to ganciclovir (mean 50% inhibitory concentration [IC50] 1.7 microM; range, 0.2-5.3 microM). Mean IC50 values (in microM) were 1.7 for group 1 isolates, 1.2 for group 2 isolates, 2.2 for group 3 isolates, and 1.7 for group 4 isolates (P > .05). Thus, acyclovir or ganciclovir prophylaxis in solid organ transplant patients did not select ganciclovir-resistant isolates of CMV.

Topics: Acyclovir; Analysis of Variance; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Microbial; Ganciclovir; Humans; Organ Transplantation; Prospective Studies; Viremia

To determine the impact of high-dose oral acyclovir on cytomegalovirus (CMV) infection or disease after liver transplantation, CMV cultures were prospectively collected for 6 months after transplantation. The incidence and timing of infection and disease in patients receiving high-dose oral acyclovir (3200 mg/day) from day 7 until 3 months after transplantation were compared with an historical control group who received no acyclovir. All patients who did not receive acyclovir (group 1, n = 12) but only 57% of those who did (group 2, n = 22) had CMV infection (P = .008). Nine (75%) group 1 but only 3 (14%) group 2 patients had positive leucocyte cultures (P = .0007). Three group 1 patients developed CMV disease; 1 group 2 patient developed CMV hepatitis. Each of these 4 patients had CMV viremia (P = .01). The frequency of CMV infection after liver transplantation appears to be reduced by high-dose oral acyclovir.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Child; Cytomegalovirus Infections; Female; Humans; Immunosuppression Therapy; Liver Transplantation; Male; Middle Aged; Time Factors; Viremia

In an effort to prevent cytomegalovirus (CMV) pneumonitis, seven consecutive CMV-seronegative lung transplant recipients of organs from seropositive donors (D+/R-) were given ganciclovir, 2.5-5 mg/kg intravenously twice daily for the first 10-21 days after transplantation, and commercial polyvalent immune globulin, 200-400 mg/kg every 7-14 days intravenously, for the first 2-3 weeks after transplantation. This regimen was followed by oral acyclovir. Six patients developed CMV viremia and all developed CMV pneumonitis. Viremia occurred later in these patients compared with D+/R- patients who received alternative forms of CMV prophylaxis or CMV-seropositive recipients who received no specific prophylaxis (P = .023 and P = .021, respectively). There was no statistical difference in incidence or time to onset of CMV pneumonitis. When given as described, prophylactic ganciclovir and immune globulin followed by oral acyclovir may have delayed CMV viremia but did not prevent it or pneumonitis in high-risk lung transplant recipients.

Topics: Acyclovir; Adult; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunoglobulins, Intravenous; Lung Transplantation; Male; Middle Aged; Pneumonia, Viral; Recurrence; Viremia

Ganciclovir is a congener of acyclovir with in vitro activity against cytomegalovirus. Ninety-seven patients with the acquired immune deficiency syndrome (AIDS) and a serious cytomegalovirus infection received ganciclovir, 3.0 to 15 mg/kg per day. Viremia cleared during drug therapy in 88 percent of patients. Viral shedding from urine and throat ceased or became inapparent during treatment in 78 percent and 68 percent of patients, respectively. Among patients with cytomegalovirus retinitis, 87 percent of evaluable patients had improvement in (30 of 60) or stabilization (22 of 60) of their disease. However, when the drug was discontinued, progression or recurrence of disease always occurred. Long-term suppressive therapy with ganciclovir, 5.0 mg/kg five to seven times weekly, prevented the recurrence of cytomegalovirus disease (p less than 0.001). The drug was eliminated by renal excretion, and in patients without renal impairment (creatinine clearance rates of more than 60 ml/minute/1.73 m2), ganciclovir has a mean half-life of 4.2 hours. Significant neutropenia and leukopenia occurred in 55 percent and 32 percent of patients, respectively.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Kinetics; Male; Opportunistic Infections; Time Factors; Viremia

Topics: Acyclovir; Antiviral Agents; COVID-19; Disease Management; Herpes Simplex; Herpesvirus 1, Human; Humans; Intensive Care Units; Male; Massive Hepatic Necrosis; Middle Aged; SARS-CoV-2; Severity of Illness Index; Viremia

Pharmacological HIV-1 reactivation to reverse latent infection has been extensively studied. However, HIV-1 reactivation also occurs naturally, as evidenced by occasional low-level viremia ("viral blips") during antiretroviral treatment (ART). Clarifying where blips originate from and how they happen could provide clues to stimulate latency reversal more effectively and safely or to prevent viral rebound following ART cessation. We studied HIV-1 reactivation in the female genital tract, a dynamic anatomical target for HIV-1 infection throughout all disease stages. We found that primary endocervical epithelial cells from several women reactivated HIV-1 from latently infected T cells. The endocervical cells' HIV-1 reactivation capacity further increased upon Toll-like receptor 3 stimulation with poly(I·C) double-stranded RNA or infection with herpes simplex virus 2 (HSV-2). Notably, acyclovir did not eliminate HSV-2-induced HIV-1 reactivation. While endocervical epithelial cells secreted large amounts of several cytokines and chemokines, especially tumor necrosis factor alpha (TNF-α), CCL3, CCL4, and CCL20, their HIV-1 reactivation capacity was almost completely blocked by TNF-α neutralization alone. Thus, immunosurveillance activities by columnar epithelial cells in the endocervix can cause endogenous HIV-1 reactivation, which may contribute to viral blips during ART or rebound following ART interruption.

Topics: Acyclovir; Anti-Retroviral Agents; Antiviral Agents; CD4-Positive T-Lymphocytes; Cell Line; Cervix Uteri; Epithelial Cells; Female; Gene Expression Regulation, Viral; HIV Infections; HIV Seropositivity; HIV-1; Humans; Primary Cell Culture; Viremia; Virus Activation; Virus Latency; Virus Replication

Herpes simplex virus (HSV)-1/2 can still be reactivated after allogeneic haematopoietic stem cell transplantation (allo-HSCT) even when the prophylactic acyclovir is used. However, the risk factors for HSV-1/2 viremia and the clinical outcomes following unmanipulated haploidentical HSCT remain unknown.. Nineteen patients with HSV-1/2 viremia and fifty-seven patients without HSV-1/2 viremia which were selected using the case-pair method after undergoing haploidentical HSCT were enrolled. We analysed the risk factors for HSV-1/2 viremia and compared the clinical outcomes between the two groups.. The risk factors for HSV-1/2 viremia included HLA disparity ≥2 loci (p=0.049) and cytomegalovirus (CMV) reactivation (p=0.028). The incidences of platelet engraftment, oral mucositis and severe haemorrhagic cystitis (HC) in patients with and without HSV-1/2 viremia were 77% and 94% (p=0.003), 78% and 13% (p=0.000), and 25% and 6% (p=0.04), respectively. Moreover, the median time to platelet engraftment in patients with and without HSV-1/2 viremia was +25days (range, +11-+80) and +17days (range, +8-+67) (p=0.004), respectively. According to the multivariate analyses, HSV-1/2 viremia was associated with delayed platelet engraftment (p=0.038), a higher incidence of oral mucositis (p=0.000) and severe HC (p=0.038). However, HSV-1/2 viremia was not associated with non-relapse mortality (34.0% vs. 31.5%, p=0.26), leukaemia-free survival (60.9% vs. 57.9%, p=0.46) and overall survival (61.2% vs. 60.7%, p=0.37).. Based on our study results, we recommend that HSV-1/2 PCR should be performed upon clinical suspicion of HSV-1/2 infection.

Topics: Acyclovir; Adolescent; Adult; Child; Child, Preschool; Cystitis; Cytomegalovirus; Cytomegalovirus Infections; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Incidence; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Retrospective Studies; Risk Factors; Transplantation, Haploidentical; Viremia; Young Adult

Topics: Abdominal Pain; Acyclovir; Aged; Biopsy, Needle; Colitis, Ulcerative; Female; Follow-Up Studies; Gastric Mucosa; Gastroscopy; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunohistochemistry; Infusions, Intravenous; Rare Diseases; Severity of Illness Index; Treatment Outcome; Viremia

Topics: Acyclovir; Antiviral Agents; Female; Fever; Herpes Simplex; Humans; Pregnancy; Pregnancy Complications, Infectious; Simplexvirus; Viremia

Varicella-zoster virus (VZV) usually causes localized zoster in adults. However, in immunocompromised patients, it can cause systemic infection accompanied by complications such as pneumonia, encephalitis, and hepatitis. Although most of critically ill patients in intensive care unit (ICU) are immunologically compromised, they are usually not considered to be at risk for systemic VZV infection.We report two cases of systemic VZV infection occurring in critically ill patients in an ICU. One patient was a 69-year-old man with Streptococcus pneumoniae-induced purpurafulminans, and the other was a 75-year-old woman with severe acute pancreatitis. During the clinical course in the ICU, characteristic vesicles with umbilical fossa appeared diffusely and bilaterally on their face, trunk, and extremities. VZV-specific IgG levels were confirmed to be elevated compared to that of the pre-onset, and a diagnosis of recurrent VZV infection was made in both patients. The patients were treated at the same ICU but did not coincide with each other; therefore a cross-infection was unlikely. They were treated with intravenous acyclovir, but the latter patient eventually died of respiratory failure.VZV infection can cause a number of serious complications, and can lead to death in some patients. Early detection and proper treatment are needed to prevent the infection from spreading out and save the patients. It might be necessary to consider antiviral prophylaxis against VZV infection for a part of critically ill patients in ICU, although the effectiveness of this approach is yet to be established.

Topics: Acyclovir; Administration, Intravenous; Aged; Animals; Antibodies, Viral; Critical Illness; Female; Herpesvirus 3, Human; Humans; Immunoglobulin G; Intensive Care Units; Male; Middle Aged; Pancreatitis; Pneumococcal Infections; Purpura Fulminans; Viremia

Disseminated neonatal herpes simplex virus (HSV) infection causes a typical systemic inflammatory response syndrome and has a high mortality rate. However, the validity of anti-inflammatory intervention against this condition remains unknown.. We sought to demonstrate the sequential changes in the pathophysiology of disseminated neonatal HSV infections.. The HSV serum copy number as well as high-mobility group box 1 (HMGB1) and cytochrome c concentrations, which predict the severity and mortality rate of sepsis, were sequentially evaluated in a patient with disseminated neonatal HSV infection caused by HSV-2.. As the patient presented with evidence of hyper-inflammation and severe illness, we empirically undertook anti-inflammatory intervention that included the administration of prednisolone, high-dose immunoglobulin, and blood exchange therapy in addition to high-dose acyclovir (ACV) therapy. The patient survived without significant neurological sequela. We found that (1) the serum concentrations of both HMGB1 and cytochrome c were extremely high, (2) temporal increases in these biomarkers were observed after admission, and (3) interestingly, the increase in HMGB1 level preceded that of cytochrome c. These results suggested that the pathophysiology of this condition changed sequentially in a dramatic manner, and the timing of our anti-inflammatory intervention was prior to the transition of pathological status from hyper-inflammation to massive apoptosis.. Anti-inflammatory intervention may only be effective if it is undertaken during the early phase of disseminated neonatal HSV infections.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Cytochromes c; DNA, Viral; Herpes Simplex; HMGB1 Protein; Humans; Infant, Newborn; Male; Pregnancy Complications, Infectious; Viral Load; Viremia

Topics: Acyclovir; Afatinib; Aged; Antineoplastic Agents; Antiviral Agents; Carcinoma, Non-Small-Cell Lung; Cystitis; ErbB Receptors; Esophagitis; Hematuria; Herpes Simplex; Humans; Intestinal Perforation; Lung Neoplasms; Male; Molecular Targeted Therapy; Neoplasm Proteins; Peritonitis; Protein Kinase Inhibitors; Quinazolines; Valacyclovir; Valine; Viremia; Virus Activation

To investigate early Epstein-Barr virus (EBV) reactivation and the outcome of preemptive therapy after allogeneic hematopoietic stem cell transplantation (allo-HSCT).. From January 2007 to January 2009, totally 277 patients after allo-HSCT were studied (haploidentical 116, unrelated 75, matched sibling 86). Conditioning regimens were mainly busulfan (BU) + cyclophosphamide (CY)/fludarabine (Flu) or total body irradiation (TBI) + CY/Flu. Antihuman thymocyte globulin (ATG) was added in haploidentical and unrelated transplants. Plasma EBV DNA was monitored once to twice weekly in the first 3 months after allo-HSCT with real time quantitative polymerase chain reaction (RQ-PCR). EBV viremia was diagnosed when EBV DNA was more than 5 × 10(2) copies/ml but without symptoms. Acyclovir (10 mg/kg, intravenous drip, 8 h) was used for preemptive therapy and immuno-suppressants were decreased if possible.. Totally 33 patients (11.9%) developed EBV viremia with a median time at day 44 (day 19 to day 84). The incidences of EBV viremia in the transplants from matched sibling, haploidentical, unrelated donors were 0, 15.5%, 20.0%, respectively. There was no significant difference between haploidentical and unrelated transplants (P = 0.09), but much less EBV viremia was seen in matched sibling transplant (P = 0.001). Twenty of 33 patients (60.6%) had complete response to preemptive therapy. The median time to reach EBV DNA negative in plasma was 11 (4 - 56) d. The median duration of preemptive therapy was 21 (14 - 60) d. Both univariate and multivariate analysis indicated that haploidentical and unrelated transplants, acute graft versus host disease (GVHD) were the risk factors for EBV viremia. Two-year overall survival in the patients with EBV viremia was significantly lower than that without EBV viremia (54.2% vs 72.1%, P = 0.006).. Our large clinical study has demonstrated that preemptive therapy with acyclovir that is guided by EBV viremia is effective in majority of the patients with high-risk for EBV reactivation after allo-HSCT, which may further decrease the risk for developing life-threatening EBV disease or post-transplantation lymphoproliferative disorder. Haploidentical and unrelated transplants, acute GVHD are the risk factors for EBV viremia which has negative impact on survival.

Topics: Acyclovir; Adolescent; Adult; Child; Child, Preschool; DNA, Viral; Epstein-Barr Virus Infections; Female; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Humans; Male; Middle Aged; Postoperative Period; Transplantation, Homologous; Viral Load; Viremia; Virus Activation; Young Adult

Immune Reconstitution Inflammatory Syndromes (IRIS) are exaggerated pathological inflammatory reactions occurring after initiation of highly active antiretroviral therapy (HAART) due to exuberant immune responses to occult or apparent opportunistic infections or cancers. In view of paucity of studies from Nigeria, we report 3 cases of IRIS presenting as disseminated infections in HIV-1 infected patients initiating HAART. The first case was a previously healthy female who developed disseminated tuberculosis after 4 weeks of regular HAART. Her HAART regimen was continued and she improved after commencement of anti-tuberculosis drugs, with evidence of progressive increase in CD4 cell count. The second case was a HAART-experienced female who stopped her drugs for 4 months. Two months after recommencement of her previous HAART regimen, she developed features of disseminated herpes zoster infection, despite evidence of decrease in viral load by 95%. HAART was continued and she recovered completely after receiving valaciclovir tablets and antibiotics. The third patient was a female student who was commenced HAART on account of chronic cough and weight loss. Three months after regular HAART, she developed features of disseminated Kaposi's sarcoma involving the skin, oropharynx and lungs, despite evidence of 42% increase in CD4 cell count. Unfortunately, she rapidly deteriorated and died during the course of management. Clinicians should be alert to the possibility of IRIS in HIV-infected patients initiated or re-initiated on HAART. There is need for future prospective studies determining risk factors for IRIS in HIV-infected patients from Nigeria.

Topics: Acyclovir; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Disease Susceptibility; Fatal Outcome; Female; Herpes Zoster; HIV Infections; HIV-1; Humans; Immune Reconstitution Inflammatory Syndrome; Nigeria; Respiratory Tract Neoplasms; Sarcoma, Kaposi; Skin Neoplasms; Tuberculosis, Miliary; Valacyclovir; Valine; Viral Load; Viremia; Young Adult

Although the standard of care in febrile neutropenic patients includes the initiation of empirical antibacterial and antifungal therapy, many patients do not respond and need further diagnostic work up and treatment. Here, we report on an immunosuppressed neutropenic patient with a prolonged episode of fever unresponsive to empirical antibacterial therapy. Herpes polymerase chain reaction revealed systemic reactivation of herpes simplex virus type 1 (HSV-1) infection and treatment with acyclovir was associated with the prompt resolution of signs and symptoms of infection. Screening for HSV in persistently febrile neutropenic patients may discover HSV reactivation that can be treated successfully by acyclovir administration.

Topics: Acyclovir; Child; Fever; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Neutropenia; Viremia; Virus Activation

Detection of Varicella-Zoster virus (VZV) DNA in plasma can facilitate the early recognition of complicated VZV-infection in immunocompromised hosts. The correlation of VZV-DNA in plasma with clinical presentations of VZV-infection and subsequent aciclovir treatment in allogeneic stem cell transplant (allo-SCT) recipients was studied. In 81 consecutive VZV-IgG positive allo-SCT recipients, VZV-DNA was measured at regular time points (1, 2 and 4 months) following allo-SCT and patient records were screened for VZV-related symptoms and aciclovir treatment. Subsequently, possible VZV-cases were studied in detail for the course of VZV-DNA and treatment effects. During the initial screening, VZV-DNA was detectable in seven patients. The survey of VZV-related symptoms revealed five additional possible VZV-cases. In cases where suitable plasma samples were available (10 out of 12), VZV-DNA was present almost simultaneously with the first clinical manifestations. No evidence of a preceding phase detectable by VZV-DNA only could be observed. Treatment with aciclovir was associated with a prompt reduction of VZV-DNA load. Detection of VZV-DNA in plasma in allo-SCT recipients accurately reflected the clinical presentation of VZV-infection and treatment with aciclovir. VZV-DNA detection in plasma of allo-SCT recipients appears clinically relevant as this may support early recognition and therapeutic management of VZV-infections following allo-SCT.

Topics: Acyclovir; Adult; Aged; Antibodies, Viral; Antiviral Agents; Cohort Studies; DNA, Viral; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Middle Aged; Polymerase Chain Reaction; Predictive Value of Tests; Sensitivity and Specificity; Stem Cell Transplantation; Time Factors; Transplantation, Homologous; Treatment Outcome; Viremia

The effect of preemptive therapy on indirect sequelae associated with cytomegalovirus (CMV) in liver-transplant recipients has not been clearly delineated.. Thirteen years of outcome with the use of preemptive therapy were assessed in a cohort of 216 consecutive liver-transplant recipients.. The incidence of major infections (31% vs. 44.3%), bacterial infections (31% vs. 39.2%), bacteremia (19% vs. 29.1%), or fungal infections (3.4% vs. 7.6%) did not differ significantly for patients with CMV infection who received preemptive therapy compared with those who never developed CMV infection and did not receive antiviral prophylaxis for CMV (P>0.20 for all variables). The rate of opportunistic infections also did not differ when patients were stratified by primary CMV infection, reactivation infection, or no CMV infection. Recurrent hepatitis C virus (HCV) hepatitis occurred in 55.6% of the patients with CMV treated with preemptive therapy and 49.8% of those without CMV infection (P>0.20). The probability of survival at 6 months, 12 months, 2 years, and 3 years was also comparable for the two groups.. Liver-transplant recipients with CMV infection, including high-risk R-/D+ patients, when followed using the preemptive therapy approach had no significant difference in meaningful outcomes such as opportunistic superinfections, HCV recurrence rates, rejection, and survival when compared with the patients in whom CMV infection never developed and who did not receive antiviral prophylaxis for CMV.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Hepatitis C; Humans; Incidence; Liver Transplantation; Longitudinal Studies; Male; Middle Aged; Opportunistic Infections; Recurrence; Survival Analysis; Viremia

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

Human herpesvirus 7 (HHV-7) is the least studied beta-herpesvirus in transplant settings. This prospective study examined the activity of HHV-7 during the first 12 weeks post-stem cell transplant in 59 paediatric patients. The presence of HHV-7, human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6) in blood was monitored weekly by a multiplex nested polymerase chain reaction. Overall, 33 (55.9%) patients had one or more surveillance blood sample(s) positive for HHV-7. In contrast to HCMV and HHV-6, no obvious peak time of reactivation was observed for HHV-7. The occurrence of HHV-7 DNAaemia showed a significant negative association with HHV-6 (P=0.022), but with no association with HCMV. A significant higher positive rate for HHV-7 was found in autologous versus allogeneic (P=0.002), and in peripheral blood versus umbilical cord/marrow (P<0.001) transplant. Acyclovir had no effect, whereas ganciclovir was associated with a lower rate of HHV-7 reactivation (P=0.009). One patient died of HHV-7 associated brain stem encephalitis. The administration of colony stimulating factor, occurrence of acute graft versus host disease, time to neutrophil and platelet engraftment showed no significant association with the occurrence of HHV-7 DNAaemia.

Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Colony-Stimulating Factors; Cord Blood Stem Cell Transplantation; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Female; Ganciclovir; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpesviridae Infections; Herpesvirus 6, Human; Herpesvirus 7, Human; Humans; Male; Polymerase Chain Reaction; Prospective Studies; Risk Factors; Roseolovirus Infections; Viremia

Shingles are caused by an endogenous or exogenous reinfection with varicella zoster virus (VZV). Up to 50% of individuals with Hodgkin's disease develop herpes zoster; however, no association could be shown between the occurrence of herpes zoster and underlying subclinical malignancies.. This study was conducted to investigate whether VZV DNA could be detected by polymerase chain reaction (PCR) in the blood of herpes zoster patients and whether there was an association between VZV viraemia and previous or concurrent neoplasias.. At least five blood samples from 28 patients with herpes zoster were investigated by internally controlled PCR enzyme-linked immunosorbent assay prior to and during therapy with aciclovir.. None of 13 patients, two with a history of neoplasia and two with a neoplasia at the time of the study, showed any signs of viraemia with VZV, and 14 patients had inconsistent viraemia, one with a history of neoplasia and two with neoplasia at the time of the study. In one patient VZV DNA was detected in the blood for 6 days. This patient died soon after from metastatic malignant melanoma.. VZV viraemia may occur during herpes zoster episodes, even in patients without evidence of immunosuppression; however, this viraemia is, in most cases, inconsistent and does not provide any specific information concerning underlying unrecognized malignancies.

Topics: Acyclovir; Adult; Aged; Base Sequence; DNA, Viral; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Incidence; Male; Middle Aged; Molecular Sequence Data; Neoplasms; Polymerase Chain Reaction; Prognosis; Prospective Studies; Risk Factors; Sampling Studies; Sensitivity and Specificity; Viremia

The most effective antiviral therapy of varicella and zoster has become acyclovir. Using polymerase chain reaction specific for VZV ORF 14, ORF 29, ORF 63 as well as nucleic acid sequence-based amplification (ORF 63, ORF 68) we tested PBMC of patients with VZV-associated diseases for the presence of viral DNA and RNA, respectively. In PBMC of patients treated with acyclovir neither DNA nor RNA was detectable already one day after the onset of therapy. In three blood sample pairs from zoster patients we were able to detect viral nucleic acid before but not after acyclovir treatment. These results confirm clinical and epidemiological data. It can be concluded that treatment with acyclovir prevents VZV replication in peripheral blood mononuclear cells.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Chickenpox; Child; DNA, Viral; Herpes Zoster; Herpesvirus 3, Human; Humans; Leukocytes, Mononuclear; Middle Aged; RNA, Viral; Viremia; Virus Replication

Organ transplant recipients who are seropositive for cytomegalovirus (CMV) and who are treated with antilymphocyte antibody (ALA) therapy have a high rate of symptomatic CMV disease. The intravenous administration of ganciclovir therapy once daily during ALA therapy decreased the incidence from 24% to 10% in patients receiving ALA as an induction therapy and from 64% to 22% in those treated for rejection. The present study was undertaken to determine whether a more intensive and sustained antiviral regimen could be more effective.. From April 1995 to December 1997, all CMV seropositive renal and liver transplant recipients who received ALA therapy were treated with intravenously administered ganciclovir (5 mg/kg/day with dose adjusted for renal dysfunction) for the length of ALA therapy and then with orally administered acyclovir (400 mg three times/day) or ganciclovir (1 gm twice/day) for 3 to 4 months. The incidence of CMV viremia and of CMV disease was determined during the 6 months after completion of ALA therapy.. Forty-one patients (35 renal and 6 liver transplant recipients) were studied. CMV disease occurred in 2 patients (4.9%), both of whom were treated for rejection; it occurred in 1 of 21 patients (4.8%) treated with orally administered acyclovir, and in 1 of 20 patients (5%) treated with orally administered ganciclovir. The only patient who developed CMV disease in the ganciclovir group had received only 26 days of oral antiviral therapy. No CMV disease was documented in the group of patients receiving ALA therapy as induction therapy. CMV viremia occurred in three patients in the acyclovir group (14.3%) and in one patient in the ganciclovir group (5%). Among renal transplant recipients only, 1 of 35 patients developed CMV disease (2.9%) and no case of CMV disease was documented in patients treated with orally administered ganciclovir. All six patients receiving two courses of ALA therapy each were free of CMV disease. Toxicity of the regimen was minimal, and antiviral resistance did not develop.. Preemptive antiviral therapy with intravenously administered ganciclovir during ALA therapy and then orally administered ganciclovir for 3 to 4 months provides virtually complete protection against the excessive rate of CMV disease that occurs in CMV seropositive allograft recipients receiving ALA therapy.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antigens, Viral; Antilymphocyte Serum; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Viremia

Three woodchucks infected persistently with the woodchuck hepatitis virus (WHV) were treated with acyclovir (ACV) to investigate the effect of inhibiting viral DNA synthesis upon the replication of an orthohepadnavirus in vivo. Normal viraemia was reduced during the treatment period in all three animals, but each responded with a distinct serum phenotype. In the most provocative case, the profile of the WHV DNAs in both the liver and serum provided a simple and novel description of the orthohepadnaviral infection for this ACV protocol. The pre-drug viraemia was rapidly cleared from the serum and replaced by virion-like particles containing predominantly minus-strand WHV DNAs. These serum DNA species had the character of replicative intermediates arrested in their elongation by ACV-mediated chain termination and were contained in particles with a buoyant density in CsCl essentially identical with virions. However, in infected hepatocytes, initiation of reverse transcription within newly formed core particles was not inhibited by the ACV treatment. Instead, an heterogeneous array of minus-strand DNAs were synthesised, each presumed to be truncated by the incorporation of one molecule of ACV monophosphate. An approximately normal level of core particles was present in the liver of this woodchuck after 26 days of the ACV protocol; excess drug-arrested nucleocapsids were steadily removed throughout the dosing period upon their envelopment and secretion as virion-like particles into the circulation. These data suggest that plus-strand DNA synthesis may not be absolutely required prior to secretion of virus from the infected cell.

Topics: Acyclovir; Animals; Antiviral Agents; Blotting, Southern; Centrifugation, Density Gradient; DNA Replication; DNA-Directed DNA Polymerase; DNA, Viral; Hepatitis B; Hepatitis B Virus, Woodchuck; Liver; Marmota; RNA Probes; Viremia; Virus Assembly; Virus Replication

To describe a case of retinal perivasculitis in an immunocompetent patient with systemic herpes simplex infection.. Polymerase chain reaction amplifications were performed for aqueous and blood samples using primers specific for the following members of the herpesvirus family: cytomegalovirus, Epstein-Barr virus, herpes simplex virus (types 1 and 2), and varicella-zoster virus. The patient was placed on intravenous acyclovir and systemic corticosteroids.. A positive polymerase chain reaction signal was found only for herpes simplex virus type 1. Vision in the left eye improved from light perception to 20/25, and signs of retinal perivasculitis resolved.. The use of molecular diagnostic modalities in clinical practice may aid in determining infectious etiologies in patients with atypical clinical manifestations.

Topics: Acyclovir; Antiviral Agents; Aqueous Humor; DNA, Viral; Eye Infections, Viral; Female; Fluorescein Angiography; Fundus Oculi; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompetence; Middle Aged; Polymerase Chain Reaction; Retinal Vein; Retinitis; Vasculitis; Viremia

This is a report on 60 consecutive patients with chronic myeloid leukemia (CML) who received an allogeneic bone marrow transplant (BMT) in this Unit. Donors were HLA-identical siblings (SIB) (n = 36) or unrelated donors (MUD) (n = 24) matched by serology for HLA A and B and by molecular biology for HLA DR. All patients were prepared with cyclophosphamide 120 mg/kg and fractionated total body irradiation 10-12 Gy. GVHD prophylaxis consisted of cyclosporin A (CsA) starting on day -7 and short-course methotrexate. Bone marrow was unmanipulated in all cases. Cytomegalovirus prophylaxis consisted of acyclovir for SIBs and foscarnet for MUDs. When compared to SIB transplants, MUD patients were younger (29 vs 36 years; P = 0.002), had younger donors (31 vs 39; P = 0.001), had a longer interval between diagnosis and BMT (1459 vs 263 days; P < 0.001) and received a smaller number of nucleated cells at transplant (3.3 vs 4.4 x 10(8)/kg; P = 0.003). More MUDs had advanced disease (50 vs 17%, P = 0.005). The median day to 0.5 x 10(9)/l neutrophils was similar in both groups (18 days for SIBs vs 17 days for MUDs; P = 0.06); the median platelet count on days +30, +50, +100 was significantly (P < 0.01) higher in SIB than in MUD patients (122 vs 38, 113 vs 50 and 97 vs 45 x 10(9)/l, respectively). Acute GVHD was scored as absent-mild, moderate, or severe, in 36, 58 and 6% of SIBs vs 25, 42 and 33% in MUD patients (P = 0.01). Chronic GVHD was comparable (P = 0.1). The actuarial risk of CMV antigenemia at 1 year was 60% in both groups. There were six deaths in SIB patients (two leukemia, two infections, one GVHD, one pneumonitis) and four deaths in MUD patients (three acute GVHD and one infection). Fifty patients survive with a median follow-up of 656 days for SIBs and 485 for MUDs. The actuarial 3-year transplant-related mortality is 12% in SIBs and 17% in MUDs (P = 0.5); the actuarial relapse is 18% in SIBs vs 6% in MUDs (P = 0.4) and 3-year survival 78% in SIBs vs 82% in MUDs (P = 0.7). This study suggests that survival of CML patients after marrow transplantation from unrelated or sibling donors is currently similar, provided the former are well matched. The increased incidence of GVHD in MUD patients is possibly compensated by a lower risk of relapse.

Topics: Acyclovir; Adolescent; Adult; Antigens, Viral; Antiviral Agents; Bone Marrow Transplantation; Cause of Death; Cytomegalovirus; Cytomegalovirus Infections; Disease-Free Survival; Female; Foscarnet; Graft vs Host Disease; Histocompatibility Testing; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukocyte Count; Life Tables; Male; Middle Aged; Neutrophils; Nuclear Family; Premedication; Prospective Studies; Recurrence; Risk; Tissue Donors; Transplantation, Homologous; Viremia

We report a patient with acute myeloblastic leukaemia who presented with a pneumonia and herpes simplex viraemia associated with primary herpes simplex virus-1 infection. The importance of detecting and treating viral infections in haematology patients is discussed.

Topics: Acyclovir; Aged; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Leukemia, Myeloid, Acute; Opportunistic Infections; Pneumonia; Viremia

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

Our data suggest that CMVIG in combination with ganciclovir effectively reduces the incidence, and delays the onset of CMV infections in seropositive lung transplant recipients. In addition, its use may be associated with less severe CMV infection and a lower incidence of bacterial or fungal opportunistic infection. Although the number of patients in the study is small, high-titer CMVIG may be more effective than standard titer immunoglobulin in the prevention of CMV disease in lung transplant recipients. Several questions remain in addition to these: What is the optimal dosage and duration of treatment with CMVIG for prophylaxis of CMV infection and disease in lung transplant recipients; Is this strategy cost-effective; Will it reduce the incidence of obliterative bronchiolitis following lung transplantation and enhance allograft survival? A prospective, random-assignment trial is warranted to answer these questions.

Topics: Acyclovir; Antibodies, Viral; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Immunization, Passive; Immunoglobulins; Immunoglobulins, Intravenous; Immunosuppressive Agents; Incidence; Lung Transplantation; Opportunistic Infections; Pneumonia, Viral; Survival Analysis; Viremia

Detection of hepadnaviral DNA in extrahepatic tissues of human and animal models of hepatitis B virus (HBV) has raised the question of whether virus replication in organs other than the liver could be targeted for the treatment of chronic hepatitis B. Since duck hepatitis B virus (DHBV) replication is dynamic in the liver, kidney, pancreas, and spleen of newly hatched ducklings infected in ovo, we used the duck model and the new antiherpesvirus agent, famciclovir (FCV), to determine whether antiviral effect of nucleoside analogues on DHBV replication is pluripotential. Day-old ducklings hatched from eggs laid by a DHBV-carrier duck were bled and administered FCV (25 mg/kg/bd) orally for periods of 1, 2, 3, 6, 9, and 12 days. Seventeen (17) hours after the last dose of each regimen the duckling(s) was bled and postmortem samples of liver, kidney, pancreas, and spleen were snap-frozen and stored at -70 degrees C. Analysis of plasma samples of ducklings treated for 2 days and longer by dot-blot hybridisation showed that levels of DHBV DNA were reduced significantly compared to levels in samples collected before treatment begun. Southern blot hybridisation of tissue DNA corroborated these results and showed that DHBV DNA replicative intermediates in all the tissues examined were reduced to levels that reflected the amount of virus released into the blood of each treated duckling. It is concluded from these results that if antiviral agents could be transformed to active metabolites in any infected tissues including the liver, replication of hepadnaviruses would be inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Animals; Animals, Newborn; Antiviral Agents; Biotransformation; Disease Models, Animal; DNA, Viral; Ducks; Eggs; Famciclovir; Guanine; Hepadnaviridae Infections; Hepatitis B Virus, Duck; Kidney; Liver; Organ Specificity; Pancreas; Poultry Diseases; Prodrugs; Spleen; Viremia; Virus Replication; Xanthine Oxidase

Cytomegalovirus (CMV) is the most common opportunistic pathogen following renal transplantation and remains a major concern in transplantation centers owing to its high morbidity and impact on renal allografts. Pending more effective antiviral drugs, efforts have been directed toward prevention strategies. We conducted a retrospective analysis to evaluate the efficacy of various prophylactic options used at our institution during the period April 1986 to August 1990. All CMV-negative patients with CMV-negative kidneys (D-R-) received screened, CMV-negative blood products (n = 19). CMV-specific immunoglobulins (CMV Ig) were used in 6 patients at increased risk for primary CMV infection and acyclovir was administered to 21 patients at an initial intravenous dose of 5 mg/kg body weight; then oral doses of 800-3200 mg per day were given according to the patients' estimated creatinine clearance. Thirty-two patients did not receive any CMV prophylactic treatment and served as controls. CMV monitoring of the patients during the first 6 months after transplantation showed an overall infection and disease rate of 81% and 38.1%, respectively, in the acyclovir-treated group. Compared with controls, the incidences of infection and disease were higher in the acyclovir-treated patients, with a significant difference for CMV infection (P = 0.002, generalized Wilcoxon test). Only 1 of the 19 D-R- patients presented with CMV infection. CMV Ig-treated patients tended to have less severe disease without any apparent reduction in infection incidence. Given the high rate of infection in patients at risk, we infer that high-dose acyclovir does not prevent CMV infection in our setting of renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acyclovir; Adolescent; Adult; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunoglobulin G; Incidence; Kidney Transplantation; Middle Aged; Opportunistic Infections; Premedication; Retrospective Studies; Transplantation, Homologous; Treatment Failure; Viremia

The effect of oral acyclovir (approximately 40 mg/kg daily in four divided doses) against primary and secondary viraemia of varicella zoster virus (VZV) was examined in 27 children susceptible to VZV who were exposed to the virus in their families and their clinical features were compared with those of 19 non-treated subjects. The infection was confirmed by a fluorescent antibody to membrane antigen assay in 11 (85%) of 13 children who received acyclovir for the first seven days after exposure to VZV and in 11 (79%) of 14 who received acyclovir for the next seven days. The geometric mean antibody titre of the former group was significantly higher than that of the latter group. Varicella developed in 10 (91%) and was subclinical in one (9%) in the former group, whereas a very mild disease occurred in three (27%) and was subclinical in eight (73%) in the latter group. The severity of varicella was significantly greater in the former group than that in the latter group. On the other hand, all of the control group developed typical varicella and their clinical features were more severe than those of the acyclovir administered group. These data indicate that oral acyclovir more effectively inhibits replication of VZV in secondary viraemia than that of the primary viraemia.

Topics: Acyclovir; Administration, Oral; Antibodies, Viral; Chickenpox; Child; Child, Preschool; Female; Humans; Infant; Male; Time Factors; Treatment Outcome; Viremia

The woodchuck was selected to study the efficacy of liver-targeted antiviral drugs on hepadnavirus replication. Nineteen woodchucks chronically infected with woodchuck hepatitis virus were treated with adenine arabinoside monophosphate or acyclovir monophosphate, either free or conjugated with the liver-targeting molecule lactosaminated human serum albumin. Circulating woodchuck hepatitis virus DNA levels remained unchanged in untreated animals and in those receiving the carrier lactosaminated human serum albumin alone; in contrast, they were consistently lower after 5 days of treatment with the antiviral drugs. Free and conjugated adenine arabinoside monophosphate were active at doses of 10 and 0.75 mg/kg, respectively, and free and coupled ACVMP were active at doses of 20 and 2.6 mg/kg, respectively. These results indicate that the dosages of adenine arabinoside monophosphate and acyclovir monophosphate required to inhibit hepadnavirus growth can be sharply reduced by coupling the drugs to lactosaminated human serum albumin.

Topics: Acyclovir; Animals; DNA, Viral; Dose-Response Relationship, Drug; Drug Carriers; Hepadnaviridae; Hepatitis, Viral, Animal; Humans; Marmota; Serum Albumin; Vidarabine Phosphate; Viremia

The toxicity of acyclovir for chick embryo fibroblasts and its effect on the replication of turkey herpesvirus (strain FC 126) and Marek's disease virus (strain HPRS 16) multiplied on fibroblast culture was studied. The influence of using acyclovir on the development of the tumour process in birds infected with a virulent Marek's disease virus was also determined. Acyclovir used in doses below 12.5 micrograms ml-1 proved to be nontoxic for chick embryo fibroblast culture. It inhibited in vitro replication of turkey herpesvirus and Marek's disease virus. It was also shown to diminish the development of tumours in birds infected with Marek's disease virus.

Topics: Acyclovir; Animals; Cell Survival; Cells, Cultured; Chick Embryo; Chickens; Fibroblasts; Herpesviridae; Herpesvirus 2, Gallid; Marek Disease; Viremia; Virus Replication

Treatment of viral infections with combinations of antiviral agents may permit administration of reduced doses of either or both drugs. Lowered doses may reduce associated toxicity. Intravenous administration of substantial doses of either human recombinant beta interferon (rHuIFN-beta) or 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) prevents development of simian varicella virus infection in African green monkeys. Daily doses of 2 X 10(6) U of rHuIFN-beta/kg inhibited clinical disease in monkeys inoculated with simian varicella virus, and doses of DHPG between 20 and 60 mg/kg per day were necessary for similar antiviral effects. Intravenous administration of combinations of rHuIFN-beta and DHPG permitted an approximately 100-fold reduction in the effective dose of rHuIFN-beta and a 10-fold reduction in the effective dose of DHPG. Analysis of data relating to viremia by using the method of the median-effect principle showed the combination of rHuIFN-beta and DHPG was strongly synergistic in treatment of this infection.

Topics: Acyclovir; Animals; Antibodies, Viral; Antiviral Agents; Chickenpox; Chlorocebus aethiops; Drug Therapy, Combination; Ganciclovir; Herpesvirus 3, Human; Interferon Type I; Recombinant Proteins; Software; Time Factors; Viremia

Acyclovir (9-(2-hydroxyethoxymethyl)guanine) administered as an intramuscular formulation twice daily at a dosage of 100 mg/kg per day prevented the development of disease in African green monkeys inoculated with simian varicella virus. Viremia, appearance of a vesicular rash, and elevations of serum transaminases, each indicative of infection, were suppressed by acyclovir treatment. Plasma concentrations of acyclovir were measured and showed rising levels after repeated intramuscular injection with a prolonged period of absorption of acyclovir into the plasma circulation. Investigation of antiviral efficacy after either intramuscular or intravenous acyclovir treatment showed both routes of administration to be effective in inhibiting simian varicella virus infection at the 100 mg/kg per day level. However, intravenous acyclovir 50 mg/kg twice daily did result in elevated values of blood urea nitrogen, creatinine, and serum transaminases.

Topics: Acyclovir; Animals; Antibodies, Viral; Antiviral Agents; Chickenpox; Chlorocebus aethiops; Drug Evaluation, Preclinical; Guanine; Herpesvirus 3, Human; Injections, Intramuscular; Injections, Intravenous; Viremia

New Zealand white rabbits less than 30 h old were inoculated subcutaneously with 10(3) 50% tissue culture infectious doses of type 2 herpes simplex virus. The animals were randomly assigned to a treatment schedule of daily intraperitoneal injections of acyclovir, beginning on the day of virus inoculation for 6 or 12 days, on post-inoculation day 1 for 6 days, or on post-inoculation day 2 for 6 days. The acyclovir was given in doses of 50 mg/kg of body weight per day. Similarly infected animals receiving daily intraperitoneal injection of Eagle minimum essential medium served as controls. All of the control animals died on day 4 or 5 after inoculation. At death they exhibited severe skin lesions, viremia, and dissemination of virus in various visceral organs and spinal as well as trigeminal ganglia. In contrast, animals treated with acyclovir failed to develop significant skin lesions, and death did not occur while treatment continued. Termination of treatment after 6 days resulted in late-onset fatal disease and virus isolation from the brain in many rabbits regardless of the treatment schedule. No such late fatality was observed and no virus could be detected from the brain when treatment was initiated on the day of virus inoculation and continued for 12 consecutive days. With respect to all of the variables studied, treatment for 12 days beginning on the day of virus inoculation was most effective.

Topics: Acyclovir; Animals; Animals, Newborn; Antiviral Agents; Brain; Guanine; Herpes Simplex; Injections, Intraperitoneal; Liver; Rabbits; Simplexvirus; Trigeminal Nerve; Viremia