High-dose Acyclovir Research Articles

Impact of High Dose Acyclovir Prophylaxis for the Prevention of Cytomegalovirus Reactivation after Pediatric Allogeneic Stem Cell Transplant

Impact of High Dose Acyclovir Prophylaxis for the Prevention of Cytomegalovirus Reactivation after Pediatric Allogeneic Stem Cell Transplant

Clinical progress note: Evaluation and management of neonatal herpes simplex virus disease.

Clinical progress note: Evaluation and management of neonatal herpes simplex virus disease.

Review of an Unusual Case of Chronic Relapsing (×6) Zoster Sine Herpete: Immediate Response to High-dose Oral Acyclovir Therapy: Efficacy of the Expedited Classic Therapeutic Trial in an Era of Digital Medicine

A 79-year-old retired physician with type II diabetes mellitus and hypercholesterolemia presented to his physician complaining of recurrent severe unilateral T10 thoracic pain. This report demonstrates the effect of early high-dose oral acyclovir therapy as a diagnostic, therapeutic challenge to assist in the early diagnosis of zoster sine herpete, herpes zoster infection without dermatomal skin rash (ZSH), a clinically covert form of the more recognized herpes zoster infection with both dermatomal pain and skin rash (HZ).

Exposure-safety relationship for acyclovir in the treatment of neonatal herpes simplex virus disease

BackgroundNeonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991. AimsDetermine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir; examine the association between acyclovir dose and exposure with adverse events (AEs). Study designWe obtained demographic information and acyclovir dosing via medical records. Acyclovir exposure was calculated using an established pharmacokinetic model. SubjectsInfants <120 days of age with neonatal HSV discharged from four academic children's hospitals. Outcome measuresWe identified clinical and laboratory adverse events (AEs). Results and conclusionsWe identified 49 infants with neonatal HSV treated with acyclovir; 42 infants had complete 21-day dosing information. Median mean daily dose was 59 mg/kg/day. Clinical AEs were common among all gestational and postnatal age groups. Rash was the most common clinical AE (37 %). Mild laboratory AEs occurred in 2–37 % of infants. The median maximum doses (mg/kg/day) were higher among infants with hypokalemia, elevated blood urea nitrogen, and thrombocytosis. For all other laboratory AEs, the median maximum doses for infants without events were higher or equal to the median maximum dose of infants with the AE. The odds of experiencing any clinical or laboratory AE did not differ by predicted acyclovir exposure for either area under the curve (AUC) or maximum concentration (Cmax) (odds ratio [OR] = 1.00 [0.98, 1.03] and OR = 1.01 [0.93, 1.12], respectively). Although AEs were common with high-dose acyclovir exposure, severe AEs were rare. Acyclovir exposure was not associated with AEs.

Varicella-zoster virus (VZV) acute retinal necrosis and recombinant zoster vaccine

Varicella zoster virus (VZV) is responsible for chickenpox. Like all herpes viruses, after primary infection it enters into latency and can be reactivated afterwards. Many forms of symptomatic reactivation of VZV exist including acute retinal necrosis (ARN), an ophthalmic emergency which can lead to blindness. ARN is treated starting with high-dose intravenous acyclovir then with oral valaciclovir for a total duration of up to 3 months. Symptomatic reactivations of VZV are public health issues. The new Swiss 2022 vaccination plan includes the recombinant vaccine Shingrix. It effectively prevents VZV symptomatic reactivations even in elderly and immuno suppressed patients.

Neonatal Herpes Simplex Virus Infection: Epidemiology and Outcomes in the Modern Era.

Over the past several decades, there have been advances in diagnosis and treatment of neonatal herpes simplex virus (HSV) disease. There has been no recent comprehensive evaluation of the impact of these advances on the management and outcomes for neonates with HSV. Clinical data for initial presentation, treatment, and outcomes were abstracted from medical records of neonates with HSV treated at Seattle Children's Hospital between 1980 and 2016. One hundred thirty infants with a diagnosis of neonatal HSV were identified. Between 1980 and 2016, high-dose acyclovir treatment for neonatal HSV infection increased from 0% to close to 95%, with subsequent decrease in overall HSV-related mortality from 20.9% to 5.6%. However, even among infants treated with high-dose acyclovir, mortality was 40.9% for infants with disseminated (DIS) disease, and only 55% of infants with central nervous system (CNS) disease were without obvious neurologic abnormalities at 24 months. Over the study period, the time between initial symptoms and diagnosis decreased. Skin recurrences were more common with HSV-2 than HSV-1 (80% vs 55%; P = .02) and in infants with lesions at initial diagnosis (76% vs 47%; P = .02). Changes in the standard of care for management of neonatal HSV disease have led to improvements in timeliness of diagnosis and outcome but mortality in infants with DIS disease and neurologic morbidity in infants with CNS disease remain high. Future research should focus on prevention of perinatal infection and subsequent recurrences.

High-Dose Intravenous Acyclovir Is Safe and Effective in the Treatment of EBV Reactivation Post Allogeneic Hematopoietic Stem Cell Transplantation

Backgroud:Reactivation of nasopharyngeal carcinoma virus (EBV) post allogeneic hematopoietic stem cell transplantation(allo-HSCT) is very common, but sustained EBV activation maybe induce EBV-associated lymphoproliferative disease (PTLD), transplant-associated hemophagocytic syndrome and thrombocytopenia after transplantation, which is extremely harmful for long-term survival. Currently, the first-line therapeutic strategy for sustained EBV activation is rituximab, but rituximab leads to increased rates of infections and delayed immune reconstitution. Therefore, for the patients with EBV-DNA copies under 1000000/mL, the pros and cons of rituximab are worth weighing.Objective:To evaluate the efficacy and safety of high-dose intravenous acyclovir in the treatment of EBV reactivation post allo-HSCT.Method:Retrospective analysis of clinical data of patients with EBV reactivation post transplantation treated with high-dose intravenous acyclovir (0.5g Q8H) in Sichuan Provincial People's Hospital from January 2019 to May 2021. A total of 49 patients post allo-HSCT from from January 2019 to May 2021 were enrolled in this study. In this population, 38 patients accepted haplo-SCT and 11 patients accepted sibling-SCT. These patients all don't suffer from PTLD and transplant-associated hemophagocytic syndrome, but are resistant to oral antiviral drugs (Acyclovir, valacyclovir, and famciclovir). Simultaneously with intravenous acyclovir, all patients received human immunoglobulin with one dose of 0.4g/kg. The clinical efficacy was evaluated as follows: Overall response(ORR) was defined as the decrease of EBV copies; Complete remission(CR) was defined as the negative turn of EBV copies; Partial response(PR), Stable disease(SD) and Progression of disease(PD) were respectively defined as the decrease, no significant change and increase of EBV copies.Results:The median transplantation time was +86 (+38 to +1587) days. The median number of EBV-DNA copies/ml was 177000 (6620-8200000). After treatment with high-dose intravenous acyclovir, 29 (59.2%) of 49 patients achieved CR, 10 (20.4%) of 49 patients achieved PR, and 10 (20.4%) of 49 patients had no response, including 2 patients with SD and 8 patients with PD. All 49 patients had responded to this regimen with 79.6% ORR. The median time of response and negative turn was 4 days (2 to 11 days) and 9 days (2 to 23 days) respectively. After 100 days for follow-up, 14 of 39 responding patients suffered from EBV activation again, and the EBV copies were higher than that when high-dose acyclovir was initiated. All 24 patients who did not turn negative were recommended with the treatment of rituximab, and 19 of 20 patients who completed treatment turned negative during the three months post acyclovir treatment. The main adverse events (AEs) of this regimen were neutropenia (CTCAE grade 2-3, 8 in 49 patients), thrombocytopenia (CTCAE grade 2-3, 10 in 49 patients), increased serum creatinine (CTCAE grade 1-2, 4 in 49 patients), phlebitis (6 in 49 patients). These AEs were all reversible, which recovered after withdrawal. There was no significant change in the counts of CD4 + T cells and CD8 + T cells before and after intravenous high-dose acyclovir.Conclusion:High-dose intravenous acyclovir is safe and effective in the treatment of EBV reactivation post allo-HSCT, although nearly half of patients still need rituximab treatment. It is a reasonable strategy for patients with oral antiviral resistance. Most patients can avoid the prescription of rituximab in the first six months post allo-HSCT, without interference of immune reconstitution. DisclosuresNo relevant conflicts of interest to declare.

Clinical presentation of herpes simplex virus infection mimicking neoplasia on the face of persons living with HIV.

The clinical presentations of herpes simplex virus (HSV) infections are varied and range from asymptomatic to a prodrome of tingling and burning followed by painful vesicles, erosions and ulcers. Resolution leads to latent infection of the sensory ganglia. HSV-1 is associated with most of the nongenital HSV-induced infections and HSV-2 is generally associated with anogenital lesions; however, lesions at either site may be caused by both viruses. In persons living with HIV (PLHIV), the lesions have been described as verrucous/hypertrophic, exophytic or vegetative and may suggest a neoplastic rather than an infective process and this can be a diagnostic dilemma in resource-limited countries with no access to confirmatory diagnostic testing for HSV. We report on two PLHIV who developed rapidly growing lesions on the face that clinically mimicked neoplasia but were found to be HSV-associated squamous proliferative lesions which responded to high dose acyclovir.

Utilization of a compaction simulator to formulate mini-tablets containing high dose of acyclovir

In this research, compaction simulator was utilized to develop high drug-loaded minitablet formulation. The formulation factors (type and ratio of filler, lubricant amount) and process factors (compression pressure, compression rate) were adjusted and the ejection force, tensile strength, thickness, compression energy, and elastic energy of mini-tablet were evaluated. The pregelatinized starch was found to be suitable base filler based on its ejection force reducing ability. When the high level of lubricant was used, tensile strength was negatively affected due to the hindrance effect. The compression pressure and compression rate influenced the ejection force by engaging in the residual die wall stress and mobility of lubricant. Meanwhile, investigation on the energy values suggested the high elasticity of pregelatinized starch. The optimized formulation could produce mini-tablets with acceptable ejection force, mechanical strength, aspect ratio, and release profile within the wide range of compression pressure and compression rate.

428 - Effect of High Dose Valacyclovir Versus Standard Dose Acyclovir on HHV-6 after Umbilical Cord Blood Transplantation

428 - Effect of High Dose Valacyclovir Versus Standard Dose Acyclovir on HHV-6 after Umbilical Cord Blood Transplantation

HSV-pneumonitis in a patient with lung cancer receiving check point inhibitors \u2013 a case report

BackgroundHerpes simplex virus (HSV) is commonly associated with oro-facial and genital manifestations. It rarely causes encephalitis and even less commonly, in heavily immunosuppressed patients, visceral disease or bronchopneumonitis. We present a case of cytologically-proven, PCR-positive HSV-1 tracheobronchitis and pneumonitis in a patient with less severe immunocompromise.Case presentationA 64 year old white man with steroid-induced diabetes mellitus and progressive small-cell bronchial carcinoma despite chemo- and immunotherapy with two checkpoint inhibitors presented with symptoms of lower respiratory tract infection. Community-acquired pneumonia was suspected and empirical broad-spectrum antibacterial treatment was initiated. Chest CT-scan revealed ground-glass opacities and tree-in bud lesions. Cytology of BAL showed extensive cytopathic effects typically caused by infection with herpes virus and PCR confirmation of HSV-1. Acute phase HSV serology was positive for IgG and borderline for IgM. The patient deteriorated clinically due to tumor progress and infection despite high-dose acyclovir therapy and died 2 weeks after admission.ConclusionsWe report an unusual case of fatal HSV-1 pneumonitis due to reactivation in a patient with lung cancer, steroid-induced diabetes and treatment with two checkpoint inhibitors. In immunosuppressed patients with non-improving pneumonia invasive diagnostic procedures are warranted including cytology and molecular diagnostics.

Topical Treatment of Acyclovir-Resistant Herpes Simplex Virus Stomatitis after Allogeneic Hematopoietic Cell Transplantation

Introduction: We report on patients who developed severe acyclovir-resistant (ACVr) herpes simplex virus 1 (HSV-1) stomatitis after allogeneic hematopoietic cell transplantation (HCT). Patients: HCT patients suffering from HSV-1 stomatitis without response after 1 week of high-dose acyclovir (ACV) were tested for ACV resistance. Patients with proven ACV resistance were treated either topically with cidofovir solution and gel or with topical foscavir cream or with intravenous foscavir. Results: Among 214 consecutive HCT patients, 6 developed severe ACVr HSV-1 stomatitis (WHO grade III n = 1, WHO grade IV n = 5). All 6 patients suffered from relapse of acute myeloid leukemia (AML) after HCT. ACVr stomatitis was treated topically with first-line (n = 4) or second-line (n = 2) cidofovir. Topical foscavir cream was applied as first-line (n = 1) or second-line (n = 1) therapy. Intravenous foscavir was used in 3 patients (first-line therapy, n = 1; second-line therapy, n = 2). Complete remission was reached by topical cidofovir (n = 3), topical foscavir (n = 1), and intravenous foscavir (n = 1), respectively. Five of the 6 patients died due to progression of leukemia. Only 1 patient survived. Conclusions: ACVr HSV-1 stomatitis is a severe complication in AML patients relapsing after HCT. It reflects the seriously impaired general condition of these patients. This analysis shows that topical treatment with cidofovir or foscavir might be a sufficient first-line therapy approach in ACVr HSV-1 stomatitis. It might serve as a less toxic alternative to intravenous foscavir.

Generalized Epilepsy with Right Hemiparesis Secondary to Herpes Encephalitis

Herpes simplex encephalitis (HSE) is a medical emergency associated with high mortality and morbidity. Definitive diagnosis is established by history, clinical examination, neuroimaging studies, supportive electroencephalogram (EEG) findings, and cerebrospinal fluid (CSF) analysis.&#x0D; A 7-year-old Malay girl with known case of right hemiplegia secondary to herpes encephalitis presented to the neuropediatric ward, in General Hospital with refractory seizure. She had a moderate learning disability and diagnosed as right hemiparesis secondary to herpes encephalitis complicated with epilepsy. She was planned for the positron emission tomography (PET) scan and to undergo operation if PET scan was feasible (Hemispherectomy). However, the patient refused for operation.&#x0D; Prompt clinical recognition is important in the HSE to prevent progressive brain tissue damage, haemorrhagic changes, and worsening of the encephalitis. Diagnosis is usually confirmed through an extensive evaluation, including a thorough clinical examination with attention to findings on mental status changes, cerebrospinal fluid (CSF) analysis, electroencephalogram (EEG) testing and findings on neuroimaging.&#x0D; Once HSE is suspected, high-dose acyclovir should be started immediately before lumbar puncture (LP), and only stopped once a definitive alternate diagnosis has been established.&#x0D; This case is reported because the patient has generalized epilepsy with right hemiparesis secondary to herpes encephalitis. Herpes encephalitis with right hemiparesis cases are quite rare.

Neonatal Herpes Simplex Virus: The Long Road to Improved Outcomes.

Herpes simplex virus (HSV) acquired during delivery places the neonate at risk for mortality or long-term neurodevelopmental disability. Exposure generally occurs from recurrent genital herpes infection, although primary infections result in the highest risk of neonatal disease. Neonates generally present in the second or third week of life with lesions. Encephalitis with seizures indicates the presence of central nervous system involvement, and other end organs may also be impacted. Clinical suspicion for neonatal HSV infection warrants immediate initiation of appropriate antiviral therapy. In the last 50 years, antiviral therapy has progressed from agents with prohibitive toxicity or cumbersome administration to herpes virus-specific agents that dramatically improve clinical outcomes with manageable toxicity. Multicenter clinical trials have demonstrated the superiority of high-dose intravenous acyclovir for acute therapy, followed by long-term oral suppressive therapy. This work has dramatically reduced morbidity and mortality from neonatal HSV, representing the benchmark for future clinical trials in neonatal pharmacotherapy.

1760. Outcomes of Acyclovir-Resistant Herpes Simplex Virus Infections in Hematologic Malignancies and Hematopoietic Cell Transplant

BackgroundAcyclovir-resistant (ACVr) herpes simplex virus (HSV) infection management is a challenge in patients with hematologic malignancies (HM) and hematopoietic cell transplant (HCT) recipients.MethodsRetrospective review of patients aged ≥ 18 years with underlying HM and/or HCT and culture-positive ACVr HSV between 1/1/2009 and December 1/2017 at a tertiary cancer center. Clinical, laboratory, microbiological, and treatment data collected.Results33 patients identified; 25 (76%) acute leukemias, 3 (9%) chronic myeloid leukemia/chronic lymphocytic leukemia (CML/CLL), 3 (9%) lymphoma, 2 (6%) other HM, and 32 (97%) had HCT. Median age of patients was 59 years (25–73) and 64% of them are females. HCT type: 22 (67%) matched unrelated donor, 3 (9%) cord blood, and 7 (21%) matched related donor. All patients were on acyclovir prophylaxis prior to diagnosis. The median time to onset of ACVr HSV infection was 147 days after transplant. Infection site: 16 (49%) oral, 10 (30%), ano-genital, 5 (15%) oral and esophagus/lung, 2 (6%) esophagus/lung. Pertinent laboratory data on day of viral culture (median/range): white blood cell (WBC) 4.6 cells/µL (0.1–85.9), absolute neutrophil count (ANC) 2,316 cells/µL (0–17,000), absolute lymphocyte count (ALC) 574.5 cells/µL (0–84,182). Serum creatinine at start and end of treatment are 0.8 mg/dL (0.32–1.98) and 0.92 mg/dL (0.36–2.7), respectively. The median duration of treatment was 30 days (4–116). Treatment: 20 (61%) foscarnet, 2 (6%) cidofovir, 4 (12%) foscarnet and cidofovir, 1 (3%) valacyclovir, 5 (15%) high-dose acyclovir, 1 (3%) unknown. 8 (24%) received adjunctive topical therapy: 5 imiquimod, 3 cidofovir. 31 included in outcome analysis (data missing in 2). Infection resolved in 15/31 (48%) while 5/31 (16%) had persistent infection. Median ANC and ALC in those with resolved vs. persistent infection (respectively): 3,082 cells/µL and 642 cells/µL vs. 1,895 cells/µL and 380 cells/µL with a trend toward lower ANC and ALC in patients with persistent infection. Overall mortality was 35% (9/31) while ACVr HSV attributable mortality was 6.4% (2/31).ConclusionACVr HSV is predominantly encountered in allogeneic HCT, particularly the unrelated donor recipients, and lower ANC/ALC may predispose to persistent infection. Disclosures All authors: No reported disclosures.

Post Transplant Prophylaxis with High Dose Valacyclovir through Day 100 Versus Day of Post Transplant Hospital Discharge Decreases Cytomegalovirus Reactivation in Adult Umbilical Cord Blood Transplant Recipients

Abstract Background: Cytomegalovirus (CMV) infection remains an important cause of morbidity and cost following umbilical cord blood transplantation (UCBT). While the introduction of letermovir represents a novel approach to CMV prophylaxis, optimal CMV management strategies remain controversial. An intensive strategy to prevent CMV disease including one week of pre-transplant ganciclovir followed by high-dose acyclovir or high-dose valacyclovir through day 100 reduced post-transplant CMV reactivation (Milano et al, Blood 2011), but this approach is costly and potentially challenging to administer. Insurance approval for outpatient high-dose valacyclovir is variable, and the pill burden of high-dose acyclovir for post-transplant patients may be unmanageable. A recent study demonstrates that the removal of pre-transplant ganciclovir does not decrease CMV reactivation rates (Hill et al, BBMT 2018). At our center we have attempted to implement the high intensity strategy described above, but for patients who are unable to obtain high-dose valacyclovir at hospital discharge, we have transitioned to standard dose 800 mg acyclovir twice daily. Additionally, in November 2016, we discontinued pre-transplant ganciclovir. To examine the efficacy of these approaches, we compared CMV outcomes among these patients. Methods: All consecutive adult CMV seropositive (CMV R+) patients who received their first double UCBT from December 2009 to January 2018 were reviewed. Patients were excluded if they had initial CMV reactivation prior to day 0 or after day 100, graft failure, death or relapse before day 100, or participated in a CMV prophylaxis trial. Starting the day of transplant, CMV R+ patients received either valacyclovir 2 grams orally 3 times daily or acyclovir 500 mg/m2 intravenously every 8 hours until able to tolerate oral medication. At hospital discharge, patients for whom valacyclovir was authorized by insurance received valacyclovir 2 grams orally 3 times daily through day 100. All others received acyclovir 800 mg orally twice a day through day 100. No patients received anti-thymocyte globulin with conditioning. All patients transplanted prior to November 2016 received pre-transplant ganciclovir, after which pre-transplant ganciclovir was discontinued. CMV reactivation was defined as any detectable PCR positive whole blood sample (checked twice weekly through day 100). Thresholds for treatment with ganciclovir or foscarnet evolved over time, but required high initial copies levels, persistent or rising DNAemia, or evidence of end-organ involvement. Acute graft-versus-host-disease (aGVHD) treatment was based on institutional guidelines and uniform for all patients. Results: Demographics of the 101 patients studied are provided in table 1. Forty-one patients received prophylaxis with high-dose valacyclovir until post-transplant discharge only (median 23 days) and 60 received valacyclovir through day 100. Between day 0 and day 100, fewer patients in the high-dose valacyclovir group (n= 20, 36%) had CMV reactivation compared to those in the acyclovir group (n= 23, 57%), p= 0.025 (figure 1). Nine patients (9%) in the acyclovir group and 6 (6%) in valacyclovir group received CMV directed treatment (p= 0.1). Patients who did or did not received pre-transplant ganciclovir had similar rates of CMV reactivation (p= 0.55 in acyclovir arm, p= 0.15 in valacylcovir arm). Overall survival (p= 0.64), neutrophil and platelet engraftment time, and incidence of grade 2-3 (p= 0.7) and grade 3-4 aGVHD (p= 0.3) were comparable between groups. Conclusions: High-dose valacyclovir through day 100 post-transplant as compared to through the day of hospital discharge post-transplant reduced CMV reactivation rates. While threshold for treatment will vary according to institutional protocol, high-dose valacyclovir through day 100 likely reduces treatment episodes. One week of pre-transplant ganciclovir does not reduce CMV reactivation rates. These data provide important baselines for future comparisons of outcomes following letermovir prophylaxis in this population. Disclosures Haverkos: Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees.

1902. A Survey of Pediatric Bone Marrow Transplant Centers Regarding Local Cytomegalovirus Prophylaxis Management Practices and Interest in a Future Randomized Trial

BackgroundCytomegalovirus (CMV) is a major source of morbidity and mortality after hematopoietic cell transplantation (HCT). A recent adult trial comparing letermovir to placebo, found this agent to be efficacious in preventing CMV reactivation with limited toxicity. Additional investigation of letermovir in pediatric HCT recipients is needed. To inform the feasibility of a pediatric trial, we surveyed bone marrow transplant (BMT) centers registered with the Children’s Oncology Group (COG) regarding their CMV management practices and interest in a pediatric trial for CMV prevention.MethodsA brief 6-item questionnaire was created using REDCap™ and distributed by email to all COG-approved BMT Centers. The initial email request was sent on March 26, 2018 to the BMT physician representative listed in the COG member roster. A follow-up request was sent on April 2, 2018. The questionnaire requested information about CMV prophylaxis strategies, including antiviral agent(s) employed, and interest in a pediatric trial of CMV prophylaxis.ResultsThe questionnaire was emailed to 89 BMT centers and was completed at 57 (64%). Of these, 23 (40%) reported giving prophylaxis to all or a subset of allogeneic/haploidentical HCT recipients. The most common indication for CMV prophylaxis (21/23) was a CMV recipient-positive, donor-negative allogeneic/haploidentical HCT recipient. Two centers provided prophylaxis to all cord blood recipients regardless of CMV status. Among these 23 prophylaxis centers, there were 10 different reported prophylaxis regimens. Fifty-one (89%) respondents confirmed an interest in a randomized trial to assess the efficacy of letermovir prophylaxis against CMV reactivation. The preferred comparator for such a trial was placebo/nothing (55%) followed by high dose acyclovir (24%).ConclusionA significant proportion (40%) of pediatric BMT centers in the United States administer CMV prophylaxis to at least a subset of their HCT recipients. The variation in prophylaxis regimens highlights the lack of comparative effectiveness data to guide clinical decisions. Nearly all centers, regardless of whether they currently provide prophylaxis, reported an interest in a trial assessing the utility of letermovir prophylaxis in children.Disclosures B. T. Fisher, Merck: Grant Investigator, Grant recipient and Research grant. C. L. K. Boge, Merck: Grant Investigator, Research grant.

The efficacy of oral acyclovir during early course of pityriasis rosea: a systematic review and meta-analysis

Background: Acyclovir has been reported as a potential therapy for pityriasis rosea (PR) in several clinical trials on the basis of evidence of the involvement of human herpes viruses 6 and 7.Objective: We evaluated the efficacy of acyclovir for abating PR skin lesions within a fixed period.Methods: We searched 4 databases for clinical trials that used oral acyclovir to treat PR and performed systematic review and meta-analysis to determine oral acyclovir’s effect on skin lesions on the 14th day after commencing treatment.Results: Five clinical trials including four randomized controlled trials were identified that compared the effects of oral acyclovir (n = 133) and nonacyclovir (n = 140) in patients with PR. Oral acyclovir significantly reduced erythema (odds ratio [OR] 11.30; 95% CI = 5.70–22.41; p < .01) and limited lesion formation (OR 8.67; 95% CI = 3.29–22.81; p < .01) compared with nonacyclovir treatment on the 14th day. These results were in agreement with the results of subgroup analysis of only high-dose oral acyclovir treatment and randomized controlled trials.Conclusion: Oral acyclovir may be a relatively safe and effective treatment in the early course of PR, and patients with PR may achieve faster symptoms control with acyclovir.

The Spanish Society of Paediatric Infectious Diseases guidelines on the prevention, diagnosis and treatment of neonatal herpes simplex infections

Neonatal herpes simplex virus infections are rare, but are associated with significant morbidity and mortality. Most newborns acquire herpes simplex virus infection in the peripartum period. For peripartum transmission to occur, women must be shedding the virus in their genital tracts symptomatically or asymptomatically around the time of delivery. There are evidence-based interventions in pregnancy to prevent the transmission to the newborn. Caesarean section should be performed in the presence of herpetic lesions, and antiviral prophylaxis in the last weeks of pregnancy is recommended to suppress genital tract herpes simplex virus at the time of delivery. The diagnosis and early treatment of neonatal herpes simplex virus infections require a high index of suspicion, especially in the absence of skin lesions. It is recommended to rule out herpes simplex virus infections in those newborns with mucocutaneous lesions, central nervous system involvement, or septic appearance. The prognosis of newborns with skin, eye, and/or mouth disease in the high-dose acyclovir era is very good. Antiviral treatment not only improves mortality rates in disseminated and central nervous system disease, but also improves the rates of long-term neurodevelopmental impairment in the cases of disseminated disease. Interestingly, a 6-month suppressive course of oral acyclovir following the acute infection has improved the neurodevelopmental prognosis in patients with CNS involvement.

Impact of High-Dose Acyclovir Cytomegalovirus Prophylaxis Failure in Abdominal Solid Organ Transplant Recipients.

To evaluate the clinical course and long-term impact of high-dose acyclovir (HD-A, 800 mg 4 times/day) cytomegalovirus (CMV) prophylaxis failure in a CMV-seropositive abdominal solid organ transplant population. Retrospective cohort study. Tertiary academic medical center. A total of 691 adults who received solid organ transplants between January 1, 2008, and June 30, 2013, without lymphocyte-depleting induction and were prescribed 3 months of HD-A prophylaxis at the time of hospital discharge. Of those patients, 54 experienced prophylaxis failure, defined as CMV detected via molecular diagnostics or on biopsy while receiving HD-A (prophylaxis failure group), and 637 did not (comparator group). Mean ± SD time to failure was 64 ± 23 days; 98% (53/54 patients) was attributable to viremia diagnosed via positive polymerase chain reaction (PCR). Of these 53 patients, 34% (18 patients) were below the quantifiable range when detected. Median initial and peak CMV PCR for quantifiable readings were 1531 IU/ml (interquartile range [IQR] less than 250-2947) and 4442 IU/ml (IQR less than 250-32,500); 19 (36%) had a single detectable CMV PCR. Treatment was required in 56% (30/54 patients), with a median duration of 63 days; 40% (12 patients) were treated with valganciclovir alone, and the remainder received intravenous ganciclovir. CMV disease resulted in hospitalization in 28% (15 patients). Immunosuppression was modified in 52% (28 patients). The rate of CMV recurrence after 100 days was significantly higher in the prophylaxis failure group (59% vs 13%, p<0.0001). Higher rates of rejection; higher rates of 1-, 3-, and 5-year graft failure; and higher rates of 1-, 3-, and 5-year mortality were noted in the prophylaxis failure group on univariate analysis (43% vs 30%, p=0.045; 8%, 17%, and 34% vs 4%, 12%, and 17%, p=0.006; and 6%, 17%, and 26% vs 1%, 6%, and 10%, p=0.003, respectively). Multivariate analysis demonstrated an increased risk of graft failure in the prophylaxis failure group (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1-3.1, p=0.0499) and a trend to increased mortality (HR 1.6, 95% CI 0.83-3.1, p=0.16). Prophylaxis failure with HD-A was mostly limited to mild viremia; however, it was associated with significantly reduced long-term graft survival, likely reflecting the negative impact of CMV viremia.