valacyclovir and 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

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

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) 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

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: 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

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

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

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