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Objectives: This study aims to compare the therapeutic effects of acyclovir nanofiber and acyclovir-clobetasol nanofiber formulations with their non-nano formulations (cream formulation) on recurrent labial herpes., Materials and Methods: Eighty patients with labial herpes lesions were divided into four groups, each receiving one of the following treatments: acyclovir-clobetasol nano patch, acyclovir-clobetasol cream, acyclovir nano patch, or acyclovir cream. Pain levels and recovery times were assessed. The Wilcoxon test compared pain levels, while the log-rank test compared healing and scabbing times., Results: Acyclovir-clobetasol nanofiber and cream, along with acyclovir nanofiber, significantly reduced symptoms compared to the acyclovir cream. The recovery and scabbing times were shorter in patients who received acyclovir-clobetasol formulations compared to those receiving acyclovir alone., Conclusion: Acyclovir-clobetasol combinations accelerated recovery times compared to acyclovir alone. Additionally, nanofiber formulations demonstrated enhanced healing efficacy over cream formulations., Trial Registration: This trial was retrospectively registered by Iranian Registry of Clinical Trials (IRCT) at 14/11/2023., Trial Registration Number: IRCT20230926059521N1., (© 2024. The Author(s).)

Background: Acyclovir treatment is an efficient prophylaxis to prevent varicella-zoster virus (VZV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT)., Aims: This single center retrospective study tried to determine if the lymphocytes immunophenotyping could help to determine the duration of prophylaxis, and evaluated complications, and associated risk factors for VZV infection., Methods and Results: Eighty-four children underwent an allogeneic HSCT, in which 77 received an acyclovir prophylaxis. Twenty-one of the 77 had a VZV infection with an incidence rate of 1.30 per 100 patients-months (exact 95% CI, 0.81 to 2.01). Among these 21 patients with VZV infection, 16 had an infection after withdrawing acyclovir prophylaxis within a median of 49 days (range, 11 days-5.8 months). Thirty-five percent of the VZV infected patients were hospitalized, 9% had a visceral dissemination, and 9% had postherpetic neuralgia. In multivariate analysis, higher VZV infection rate was associated with conditioning regimen with total body irradiation, immunoglobulin substitution, and antithymocyte globulin. The incidence of VZV infection increased significantly when patients had a CD4+ lymphocytes count below 23% (cHR 3.28 [95% CI, 1.09-9.81]; p = 0.03) or a CD4 + /CD8 + ratio less than 0.9 (cHR 3.13 [95% CI, 1.04-9.36]; p = 0.04) at the time of stopping acyclovir prophylaxis., Conclusion: After cessation of acyclovir prophylaxis, VZV reactivation can occur and be responsible for morbidity after allogeneic HSCT. This study suggests that the proportion of CD4+ lymphocytes and the CD4 + /CD8 + ratio can inform decisions about the duration of acyclovir prophylaxis after allogeneic HSCT to prevent VZV reactivation., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Background: Viral pneumonia, a pressing global health issue, necessitates innovative therapeutic approaches. Acyclovir, a potent ring-opening antiviral agent with broad-spectrum activity, faces water solubility, oral bioavailability, and drug resistance challenges. The aim of this study was to increase the efficacy of acyclovir through respiratory delivery by encapsulating it within albumin-modified lipid nanoparticles and formulate it as a spray., Methods: Nanoparticles was synthesized via the reverse evaporation method; its physicochemical characteristics were rigorously evaluated, including particle size, zeta potential, morphology, encapsulation efficiency, drug loading, and release profile. Furthermore, the cytotoxicity of nanoparticles and its therapeutic potential against viral pneumonia were assessed through cellular and animal model experiments. Result s: Nanoparticles exhibited a spherical morphology, with a mean particle size of 97.48 ± 5.36 nm and a zeta potential of 30.28 ± 4.72 mv; they demonstrated high encapsulation efficiency (93.26 ± 3.27%), drug loading (11.36 ± 0.48%), and a sustained release profile of up to 92% under neutral conditions. Notably, nanoparticles showed low cytotoxicity and efficient intracellular delivery of acyclovir. In vitro studies revealed that nanoparticles significantly reduced interleukin-6 levels induced by influenza virus stimulation. In vivo , nanoparticles treatment markedly decreased mortality, attenuated the inflammatory markers interleukin-6 and tumor necrosis factor-α levels, and mitigated inflammatory lung injury in mice with viral pneumonia., Conclusions: In this study, albumin was modified with polyethylene glycol (PEG) containing cationic lipid nanoparticles (LN) to prepare albumin-modified lipid nanoparticles encapsulating acyclovir (ALN-Acy), which can effectively deliver Acy into tissues and cells, prolong the survival of mice, and reduce lung injury and inflammatory factors. White albumin LN can be used as efficient drug delivery carriers, and the delivery of Acy via albumin LN is expected to be a therapeutic strategy for treating inflammatory diseases., (© 2024 The Author(s). Published by IMR Press.)

Purpose: The objective of this study was to investigate whether different dispensing processes can alter the physicochemical and structural (Q3) attributes of a topical cream product, and potentially alter its performance., Methods: Acyclovir cream, 5% (Zovirax®) is sold in the UK and other countries in a tube and a pump packaging configurations. The structural attributes of the cream dispensed from each packaging configuration were analyzed by optical microscopy, confocal Raman microscopy and cryo-scanning electron microscopy. Rheological behavior of the products was also evaluated. Product performance (rate and extent of skin delivery) was assessed by in vitro permeation tests (IVPT) using heat-separated human epidermis mounted in static vertical (Franz-type) diffusion cells., Results: Differences in Q3 attributes and IVPT profiles were observed with creams dispensed from the two packaging configurations, even though the product inside each packaging appeared to be the same in Q3 attributes. Visible globules were recognized in the sample dispensed from the pump, identified as dimethicone globules by confocal Raman microscopy. Differences in rheological behaviour could be attributed to these globules as products not dispensed through the pump, demonstrated a similar rheological behaviour. Further, IVPT confirmed a reduced rate and extent to delivery across human epidermis from the product dispensed through a pump., Conclusions: Different methods of dispensing topical semisolid products can result in metamorphosis and Q3 changes that may have the potential to alter the bioavailability of an active ingredient. These findings have potential implications for product developers and regulators, related to the manufacturing and comparative testing of reference standard and prospective generic products dispensed from different packaging configurations., (© 2024. The Author(s).)

Background: Systematic treatment with intravenous acyclovir is usually given when varicella zoster virus (VZV) DNA is isolated in cerebrospinal fluid (CSF), indicating central nervous system (CNS) involvement. Our study aimed to describe therapeutic management and acute kidney injury (AKI) occurrence during acyclovir treatment of VZV infection with CNS involvement., Methods: Multicentre, retrospective study including all patients from 2010 to 2022 with VZV DNA in CSF. Patient management and outcomes were compared according to clinical presentation and indications for intravenous acyclovir: i) definite (encephalitis, myelitis or stroke, peripheral nervous system (PNS) with ≥ 2 roots, herpes zoster ≥ 3 dermatomes, immunosuppression), ii) questionable (1 or 2 dermatomes) or iii) no indication (other situations)., Results: 154 patients were included (median age 66 (interquartile range 43-77), 87 (56%) males); 60 (39%) had encephalitis, myelitis or stroke, 35 (23%) had PNS involvement, 37 (24%) had isolated meningitis, 14 (9%) had isolated cutaneous presentation, and 8 (5%) had other presentations. Overall, 128 (83%) received intravenous acyclovir for more than 72 h. AKI occurred in 57 (37%) patients. Finally, 42 (27%) and 25 (16%) patients had respectively no or a questionable indication for intravenous acyclovir, while 29 (69%) and 23 (92%) of them received it for more than 72 h, with AKI in 13 (35%) and 13 (52%) patients, respectively. In-hospital mortality was 12% ( n  = 18), and no deaths were reported in isolated meningitis., Conclusions: Intravenous acyclovir is widely prescribed when VZV DNA is isolated in CSF, regardless of the clinical presentation, with a high rate of AKI. Further studies are needed to better define the value of intravenous acyclovir in isolated VZV meningitis.

This study focuses on the preparation of layered bacterial nanocellulose (BNC) patches for drug delivery and wound healing in the context of herpes labialis. Nanostructured patches were prepared by selective aqueous diffusion of acyclovir (ACV, antiviral drug), hyaluronic acid (HA, skin healing promoter), and glycerol (GLY, plasticizer and humectant) in the BNC network, followed by assembly into trilayered patches with ACV on the central layer of the patch (ACV T ) or divided between two layers (ACV H ), to modulate drug release. Both patches showed good layers' adhesion and thermal stability (125 °C), UV barrier properties, good static (Young's modulus up to 0.9 GPa (dry) and 0.7 GPa (wet)) and dynamic mechanical performance, and adhesion strength (21 kPa) comparable to or higher than other materials and commercial adhesives for wound healing. In vitro drug dissolution showed faster ACV release from the ACV H patch (77 ± 5 %, 10 min) than from the ACV T one (50 ± 7 %), suggesting efficient drug delivery. ACVH closely resembled a commercial cream formulation in terms of release and permeation profiles. The patches were non-cytotoxic toward L929 fibroblasts, promoting cell adhesion and wound closure (in vitro). These results underscore the dual-action potential of the layered patches for managing herpetic lesions., Competing Interests: Declaration of competing interest The authors proclaim that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Herpes simplex virus (HSV) infections necessitate careful management of urinary dysfunction and retention, which are underestimated conditions. Here, we present a rare case of HSV encephalomyeloradiculitis in a 76-year-old man, whose initial symptoms included urinary dysfunction and retention that alone lasted for approximately 1 week. Unlike in meningoencephalitis, high fever and headache were absent; however, the patient subsequently developed cauda equina syndrome and consciousness disturbance. Gadolinium-enhanced spinal MRI suggested enhanced cauda equina at the L2/3 level. Upon admission, he was treated for meningoencephalitis with acyclovir and steroid pulse therapy. Subsequent cerebrospinal fluid analysis result was positive for HSV DNA. A ‍brain MRI conducted 1 week after admission displayed high-intensity lesions in the white matter of the right temporal lobe, confirming HSV encephalomyeloradiculitis. These treatments were highly effective and gradually improved the patient's condition. He was discharged 1 month after hospitalization, and the urinary catheter was removed 2 weeks later. HSV infections can cause life-threatening encephalomyeloradiculitis. Therefore, both neurologists and urologists must pay attention to their occurrence and characteristics in clinical settings.

Background: Acute functional decline is a common reason for hospital admission for older people, often caused by an acute deterioration of an underlying chronic illness. However, occasionally a rare condition is detected., Case Presentation: A woman in her eighties was admitted to hospital with acute functional decline. Hyponatraemia, urinary tract infection and pulmonary embolism were initially diagnosed. She developed increasing difficulties in using her legs, and assessment led to the diagnosis of varicella- zoster virus myelitis, which was treated with intravenous acyclovir. After a brief stay in the rehabilitation unit, the patient's condition acutely deteriorated, leading to readmission with neurovascular septic embolism and microvascular haemorrhage in the brain. Anticoagulation was terminated. After 52 days she was discharged to a nursing home for further rehabilitation., Interpretation: Our article presents a case of acute functional decline caused by a rare condition. Collaboration between the geriatric, neurological and infectious disease departments was needed. When treated rapidly with targeted therapy, the prognosis for myelitis is often good.

Combining different drugs synergistically is an essential aspect of developing effective treatments. Although there is a plethora of research on computational prediction for new combination therapies, there is limited to no research on combination therapies in the treatment of viral diseases. This paper proposes AI-based models for predicting novel antiviral combinations to treat virus diseases synergistically. To do this, we assembled a comprehensive dataset comprising information on viral strains, drug compounds, and their known interactions. As far as we know, this is the first dataset and learning model on combination therapy for viruses. Our proposal includes using a random forest model, an SVM model, and a deep model to train viral combination therapy. The machine learning models showed the highest performance, and the predicted values were validated by a t-test, indicating the effectiveness of the proposed methods. One of the predicted combinations of acyclovir and ribavirin has been experimentally confirmed to have a synergistic antiviral effect against herpes simplex type-1 virus, as described in the literature., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Majidifar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A 67-year-old man had taken the janus kinase (JAK) inhibitor, tofacitinib, for ulcerative colitis. He was referred to our department for a refractory ulcer on his lower leg. We suspected vasculitis and performed skin biopsy. Histopathological examination showed multinucleated giant cells in the epidermis and fibrinoid degeneration of small vessels in the upper dermis. Varicella zoster virus (VZV) DNA was detected by polymerase chain reaction and we diagnosed the patient with atypical vasculitis-like herpes zoster. The patient was treated with oral valacyclovir, but the rash persisted and took 2 months to heal. Immunostaining using anti-VZV antibody was positive mainly in epidermal keratinocytes, but was also observed to be positive in cells in the dermis. We further performed RNA in situ hybridization using a VZV ORF9 mRNA probe and clearly showed that the distribution of VZV mRNA extended into the dermis, including the dermal vessel walls and the eccrine sweat glands as well as the epidermis. The internal administration of JAK inhibitors may induce regional widespread VZV infection including vessels and involved in the formation of prolonged vasculitis-like manifestation. RNA in situ hybridization can be a potent tool for detecting the spread of VZV infection in the skin., (© 2024 Japanese Dermatological Association.)

Antiviral use has been linked to encephalopathy and elevated serum creatinine concentrations in individuals with chronic kidney disease (CKD) in case reports. Using linked healthcare data in Ontario, we conducted a population-based cohort study on adults aged ≥66 years not receiving dialysis and newly prescribed oral acyclovir, valacyclovir, or famciclovir in the outpatient setting (2008-2022) at higher versus lower doses. The primary composite outcome, a hospital visit with encephalopathy or acute kidney injury (AKI) within 14 days of initiating antiviral treatment, was examined in a primary cohort. AKI was assessed in a secondary cohort of older adults with CKD with available linked hospital-based laboratory (lab) data. We used inverse probability of treatment weighting on the propensity score to balance comparison groups on baseline health. Weighted risk ratios (RR) and risk differences (RD) were obtained using modified Poisson and binomial regression. In the primary cohort, higher- versus lower-dose antiviral was not associated with an increased 14-day risk of hospital visit with encephalopathy or AKI. However, Higher- versus lower-dose antiviral was associated with a higher risk of a hospital visit with AKI when assessed using lab values (weighted number of events, 70 of 8407 [0.83%] versus 18 of 8230 [0.22%], respectively; weighted RR, 3.83 [95% CI, 1.87-7.87]; weighted RD, 0.62% [95% CI, 0.37%-0.86%]). In older adults with CKD, starting an antiviral at a higher versus lower dose was associated with a higher risk of AKI, although the absolute risk of this event was <1%., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Genital herpes, caused by herpes simplex virus type 2 (HSV-2), affects nearly 500 million people, mostly women. Since the main route of transmission is sexual contact, the development of an acyclovir extended-release vaginal microbicide would be a suitable tool for the prevention of virus transmission. In this work, we evaluated the potential of three polymers with different characteristics (chitosan, xanthan gum and ethyl cellulose) for obtaining acyclovir extended-release vaginal tablets. By combining the polymers, certain useful synergies were observed to modify their mucoadhesive capacity and control drug release. In the swelling studies, it observed that a polyelectrolyte complex with more moderate swelling and sustained gelation was formed between chitosan and xanthan gum exclusively in acidic medium (simulated vaginal fluid). This complex allowed prolonging the mucoadhesion of the tablets in ex vivo studies performed with vaginal mucosa, which would translate into better retention in the vagina after administration. In addition, the combination of chitosan and xanthan gum allowed obtaining a controlled release of acyclovir for 5 days, regardless of the pH of the medium, which would guarantee that drug release continues even in the presence of seminal fluid., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The patient, a 36-year-old female, had no previous history of shingles. She was admitted to the hospital due to nausea and lightheadedness. Upon admission, she was diagnosed with bilateral medial medullary infarcts. She received treatment with intravenous edaravone and argatroban, as well as antiplatelet therapy with aspirin and clopidogrel. However, her dysphagia, dysarthria, and paraplegia worsened. Due to changes in the lesion of the basilar artery on brain ‍MRA, we suspected the possibility of basilar artery dissection, and discontinued antiplatelet therapy. Subsequent imaging studies suggested vasculitis. After examining the cerebrospinal fluid, we diagnosed varicella-zoster virus (VZV) vasculopathy. Based on this diagnosis, we administered steroid pulse therapy for three days, started intravenous acyclovir, and resumed antithrombotic therapy with clopidogrel. Prednisone was administered for five days. Biochemical tests revealed an elevated D-dimer level. Due to the presence of lower extremity venous thrombus, clopidogrel was replaced with apixaban. The acyclovir infusion was discontinued due to observed acyclovir-induced neutropenia. These treatments improved neurological symptoms, circumflex thickening of the basilar artery, and contrast effects in the same area. On the 70th day, the patient was transferred to the hospital for rehabilitation. It is important to consider VZV angiopathy as a potential cause of juvenile cerebral infarction accompanying progressive basilar artery stenosis, regardless of the presence or absence of a skin rash.

A 78-year-old man was admitted to the hospital with a 4-day history of fever and confusion. Physical examination revealed oral dryness and decreased skin turgor. Blood tests showed hyponatremia (121.5 ‍mEq/l), and cerebrospinal fluid examination revealed positivity for herpes simplex virus 1 (HSV-1) via polymerase chain reaction. He was diagnosed with herpes simplex encephalitis and initiated acyclovir treatment. The hyponatremia was diagnosed as cerebral salt wasting syndrome (CSWS) and treated with hypertonic saline infusion and fludrocortisone. The cerebrospinal fluid HSV-1 DNA became negative, and the serum sodium levels normalized. Hyponatremia complicated with encephalitis is often caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), whereas CSWS is rare, mostly observed in tuberculous meningitis. Differentiating between the SIADH and CSWS is important as they require distinct therapeutic strategies.

We present a case of a primigravida in her 30s who had a caesarean delivery of dichorionic diamniotic twins at 33 weeks of gestation. Her postpartum course was complicated by a herpes simplex virus (HSV) infection of her nipple, found after her neonates were diagnosed with HSV encephalitis. She was evaluated at her 3-week postpartum visit and reported that her neonates were concurrently admitted to the neonatal intensive care unit with disseminated neonatal HSV-1. The patient and her partner were in a monogamous relationship with no known history of HSV. Physical examination demonstrated a vertical fissure on the face of her right nipple and a small cluster of vesicles on her left hand. PCR swabs of the lesions were positive for HSV-1 at both locations. The patient was started on oral valacyclovir 1000 mg two times per day, topical acyclovir ointment applied 4-6 times per day and mupirocin ointment applied 3 times per day to her breast with resolution of her breast lesions. She was able to continue expressing her breastmilk with the help of a pump and then resumed breastfeeding once her infection was cleared. Her infants recovered after prolonged parenteral antiviral therapy with age-appropriate development at follow-up., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study evaluated the presence of Epstein-Barr virus type 1 (EBV-1) DNA in patients living with HIV, before and after three different topical therapy protocols for oral hairy leukoplakia (OHL)., Methods: The sample consisted of five patients treated with topical solution of 25% podophyllin resin; six with 25% podophyllin resin plus 5% acyclovir cream; and four with 25% podophyllin resin plus 1% penciclovir cream. DNA was extracted from OHL scrapings and amplified by the PCR using specific primers for EBV-1 (EBNA-1)., Results: Clinical healing of OHL lesions was observed across all treatment groups over time. At baseline, EBNA-1 was detected in all OHL lesions. After treatment, OHL samples from three patients treated with 25% podophyllin resin plus 5% acyclovir cream and from one patient treated with 25% podophyllin resin plus 1% penciclovir cream exhibited negative EBNA-1 viral gene encoding. Despite the clinical resolution of OHL, 11 patients (73.3%) showed EBNA-1 positivity immediately after the lesion disappeared. Three patients (20%) treated with podophyllin resin displayed both EBNA-1 positivity and a recurrence of OHL, in contrast to no recurrence in the other two groups., Conclusions: These findings suggest potential associations between treatment formulations, EBNA-1 persistence, and the recurrence of OHL lesions., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To characterize differences between Herpes Simplex virus encephalitis and Varicella-Zoster virus encephalitis (HSVE and VZVE) and other aetiologies of infectious encephalitis (IE), and to investigate the impact of time-to-aciclovir (ACV) start, ACV dose and duration on outcome., Methods: We compared 132 HSVE, 65 VZVE and 297 other IE enrolled in a prospective cohort (ENCEIF). We estimated associations between time-to-ACV start, dose or duration and outcome through adjusted odds ratio (aOR) using logistic regression analysis., Results: Prevalence of immunodepression differed among aetiologies: 15/65 (23%) for VZVE, 13/132 (10%) for HSVE and 30/297 (10%) for other IE (p <0.05), as was presence of seizure at admission: 27/132 (20%) for HSVE, 4/65 (6%) for VZVE and 43/297 (14%) for other IE (p <0.05). Poor outcome at hospital discharge (Glasgow outcome scale ≤3) differed among the three groups: 40/127 (31%) for HSVE, 12/65 (18%) for VZVE and 38/290 (13%) for other IE (p <0.05). Time-to-ACV start was associated with outcome in HSVE (aOR 3.61 [1.25-10.40]), but not in VZVE (aOR 0.84 [0.18-3.85]). Increased ACV dose was not associated with outcome among HSVE (aOR 1.25 [0.44-3.64]) nor VZVE (aOR 1.16 [0.24-5.73])., Discussion: HSVE and VZVE are distinct in clinical presentation, outcome and prognostic factors. The impact of early ACV initiation was more apparent for HSVE than for VZVE; however, this could be because of VZVE's smaller sample size and lower outcome rate leading to low statistical power or because of potential distinct IE pathophysiology., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate the physicochemical compatibility of caffeine citrate and caffeine base injections with 43 secondary intravenous (IV) drugs used in Neonatal Intensive Care Unit (NICU) settings., Methods: Caffeine citrate (20 mg/mL or 10 mg/mL) or caffeine base injection (10 mg/mL) were mixed in a volume ratio of 1:1 with the secondary drug solution to simulate Y-site co-administration procedures in NICUs. Physical compatibility was evaluated based on visual observation for 2 h, against a black and white background and under polarised light, for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from caffeine concentration measurements, using a validated high-performance liquid chromatography assay., Results: Six of the 43 secondary drugs tested (aciclovir, amphotericin (liposomal), furosemide, hydrocortisone, ibuprofen and ibuprofen lysine) were physically incompatible with caffeine citrate undiluted injection (20 mg/mL), at their high-end, clinically relevant concentrations for NICU settings. However, when tested at lower concentrations, hydrocortisone (1 mg/mL) was physicochemically compatible, whereas furosemide (0.2 mg/mL) was physically incompatible with caffeine citrate. The six drugs which showed physical incompatibility with caffeine citrate 20 mg/mL injection were also physically incompatible with caffeine citrate 10 mg/mL solution. All 43 secondary drugs tested were physicochemically compatible with caffeine base injection., Conclusions: Most secondary test drugs, except aciclovir, amphotericin (liposomal), furosemide, hydrocortisone, ibuprofen and ibuprofen lysine, were physicochemically compatible with caffeine citrate injection. Caffeine base injection was physicochemically compatible with all 43 test drugs tested., (© 2024. The Author(s).)

Purpose: To develop a toolkit of test methods for characterizing potentially critical quality attributes (CQAs) of topical semisolid products and to evaluate how CQAs influence the rate and extent of active ingredient bioavailability (BA) by monitoring cutaneous pharmacokinetics (PK) using an In Vitro Permeation Test (IVPT)., Methods: Product attributes representing the physicochemical and structural (Q3) arrangement of matter, such as attributes of particles and globules, were assessed for a set of test acyclovir creams (Aciclostad® and Acyclovir 1A Pharma) and compared to a set of reference acyclovir creams (Zovirax® US, Zovirax® UK and Zovirax® Australia). IVPT studies were performed with all these creams using heat-separated human epidermis, evaluated with both, static Franz-type diffusion cells and a flow through diffusion cell system., Results: A toolkit developed to characterize quality and performance attributes of these acyclovir topical cream products identified certain differences in the Q3 attributes and the cutaneous PK of acyclovir between the test and reference sets of products. The cutaneous BA of acyclovir from the set of reference creams was substantially higher than from the set of test creams., Conclusions: This research elucidates how differences in the composition or manufacturing of product formulations can alter Q3 attributes that modulate myriad aspects of topical product performance. The results demonstrate the importance of understanding the Q3 attributes of topical semisolid drug products, and of developing appropriate product characterization tests. The toolkit developed here can be utilized to guide topical product development, and to mitigate the risk of differences in product performance, thereby supporting a demonstration of bioequivalence (BE) for prospective topical generic products and reducing the reliance on comparative clinical endpoint BE studies., (© 2024. The Author(s).)

Objective: Extravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the present study, we presented a neonate with soft tissue damage due to acyclovir extravasation., Case Report: A female newborn (Iranian, Asian) with gestational age 37 +2  weeks and breech presentation was born by Cesarean delivery from a mother with a recent history of Herpes simplex virus (HSV) infection (Yas Women's Hospital, Tehran, Iran). Intravenous administration of acyclovir was initiated through a peripheral catheter inserted on the dorsal side of the left hand. A few minutes after the second dose, the patient showed a diffused firm swelling, local discoloration, and induration in the dorsum of the hand. The peripheral catheter was removed immediately. Hyaluronidase was injected subcutaneously in five different regions around the catheterization site. Intermittent limb elevation and cold compression (for 10 minutes) were applied. Serial follow-ups and examinations were performed hourly to check limb inflammation, ischemia, and compartment syndrome. The limb swelling and discoloration significantly improved 4 hours after the second dose of hyaluronidase., Conclusion: Early diagnosis of acyclovir extravasation and immediate management could prevent severe complications in neonates. Further studies are needed to suggest a standard approach and treatment protocol for acyclovir extravasation., (© 2024. The Author(s).)

Hemophagocytic lymphohistiocytosis is a severe hyperinflammatory syndrome that can be potentially life-threatening without appropriate treatment. Although viral infection is the most common trigger of hemophagocytic lymphohistiocytosis, cases of herpes simplex virus type 1-induced hemophagocytic lymphohistiocytosis are rare in adults. This study aims to provide a comprehensive overview of the clinical characteristics and treatment outcomes associated with HSV-1-induced HLH. We herein report an adult case of hemophagocytic lymphohistiocytosis caused by herpes simplex virus type 1, diagnosed on the basis of peripheral blood metagenomic next-generation sequencing results. The patient exhibited a favorable response to treatment, involving dexamethasone, intravenous immunoglobulin, and acyclovir. Notably, etoposide administration was deemed unnecessary, and there has been no recurrence of the disease within the year following treatment. Early and sensitive recognition, rapid and precise diagnosis, and timely and appropriate treatment facilitated the successful treatment of this case., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Herpes stromal keratitis (HSK) is an immune-mediated corneal inflammation that occurs after a herpes simplex virus infection. This paper aims to systematically identify and compare interventions for treating HSK and their patient outcomes., Methods: This systematic review followed the PRISMA methodology. Online databases were searched to obtain all relevant papers. Two independent reviewers screened through 168 records. Seven papers were included and used for data extraction. A qualitative analysis was conducted., Results: HSK patients receiving prednisolone phosphate and acyclovir showed a higher treatment success rate and significantly longer time to failure compared to patients receiving only acyclovir ( P  < .001). No difference in resolution time was found between oral and topical acyclovir. Between groups receiving dexamethasone and flurbiprofen, resolution occurred in 93% and 67% of patients, and BCVA (LogMAR) improved from 1.0 to 0.30 and 0.48, respectively. BCVA improved in both cyclosporine-A ( P  < .001) and its control (prednisolone) groups ( P  = .002). A tacrolimus treatment group showed greater improvement in BCVA compared to its control (prednisolone) group ( P  < .001)., Conclusion: Corticosteroids and antivirals managed HSK most effectively only when used concurrently. Oral acyclovir showed similar effectiveness to its ointment counterpart, a preferable alternative for easier administration. Corticosteroid use could induce greater therapeutic benefits when tapered in concentration and frequency and administrated for at least 10 weeks. Anti-inflammatory drugs including flurbiprofen, cyclosporine-A, and tacrolimus could be safe and effective for treating HSK. Future long-term follow-up and RCTs could provide insights on the therapeutic benefits of these potential alternatives.

The field of nasal drug delivery gained enormously on interest over the past decade. Performing nasal in vivo studies is expensive and time-consuming, but also unfeasible for an initial high-throughput compound and formulation screening. Therefore, the development of fast and high-throughput in vitro models to screen compounds for their permeability through the nasal epithelium and mucosa is constantly expanding. Yet, the protocols used for nasal in vitro permeability studies are varying, which limits the comparability and reproducibility of generated data. This project aimed to elucidate the influence of different culture and assay parameters of RPMI 2650 cells grown under air-liquid interface (ALI) conditions on the transepithelial electrical resistance (TEER) and apparent permeability (P app ) values of five selected reference compounds, covering the range of low to moderate to high permeability. The influence of the passage number, seeding density, and timepoint of airlift was minimal in our approach, while the substrate pore density had a significant influence on the P app values of carbamazepine, propranolol, and metoprolol, classified as highly permeable compounds, but not on atenolol and aciclovir. Elevation of the experimental concentration of carbamazepine, propranolol, and metoprolol in the donor compartment had an increasing effect on the P app values, while prolonging the assay time did not have a significant influence. Based on the results reported here, RPMI 2650 cells cultured under ALI conditions offer the possibility of a standardized high-throughput screening model for small molecules and their formulations for in vitro drug permeation studies to predict and select optimal conditions for their nasal delivery., (© 2023. Controlled Release Society.)

Background: Valganciclovir (valG), a cytomegalovirus (CMV) prophylactic agent, has dose-limiting side effects. The tolerability and effectiveness of valacyclovir (valA) as CMV prophylaxis is unknown., Methods: We conducted a randomized, open-label, single-center trial of valA versus valG for all posttransplant CMV prophylaxis in adult and pediatric kidney recipients. Participants were randomly assigned to receive valA or valG. Primary endpoints were the incidence of CMV viremia and side-effect related drug reduction with secondary assessment of incidence of EBV viremia., Results: Of the 137 sequential kidney transplant recipients enrolled, 26 % were positive and negative for CMV antibody in donor and recipient respectively. The incidence of CMV viremia (4 of 71 [6 %]; 8 of 67 [12 %] P = 0.23), time to viremia (P = 0.16) and area under CMV viral load time curve (P = 0.19) were not significantly different. ValG participants were significantly more likely to require side-effect related dose reduction (15/71 [21 %] versus 1/66 [2 %] P = 0.0003). Leukopenia was the most common reason for valG dose reduction and granulocyte-colony stimulating factor was utilized for leukopenia recovery more frequently (25 % in valG vs 5 % in valA: P = 0.0007). Incidence of EBV viremia was not significantly different., Conclusions: ValA has significantly less dose-limiting side effects than valG. In our study population, a significant increase in CMV viremia was not observed, in adults and children after kidney transplant, compared to valG., Trial Registration Number: NCT01329185., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aciclovir is considered the first-line treatment against Herpes simplex virus (HSV) infections in new-borns and infants. As renal excretion is the major route of elimination, in renally-impaired patients, aciclovir doses are adjusted according to the degree of impairment. However, limited attention has been given to the implications of immature renal function or dysfunction due to the viral disease itself. The aim of this investigation was to characterize the pharmacokinetics of aciclovir taking into account maturation and disease processes in the neonatal population. Pharmacokinetic data obtained from 2 previously published clinical trials (n = 28) were analyzed using a nonlinear mixed effects modeling approach. Post-menstrual age (PMA) and creatinine clearance (CL CR ) were assessed as descriptors of maturation and renal function. Simulation scenarios were also implemented to illustrate the use of pharmacokinetic data to extrapolate efficacy from adults. Aciclovir pharmacokinetics was described by a one-compartment model with first-order elimination. Body weight and diagnosis (systemic infection) were statistically significant covariates on the volume of distribution, whereas body weight, CL CR and PMA had a significant effect on clearance. Median clearance varied from 0.2 to 1.0 L/h in subjects with PMA <34 or ≥34 weeks, respectively. Population estimate for volume of distribution was 1.93 L with systemic infection increasing this value by almost 3-fold (2.67 times higher). A suitable model parameterization was identified, which discriminates the effects of developmental growth, maturation, and organ function. Exposure to aciclovir was found to increase with decreasing PMA and renal function (CL CR ), suggesting different dosing requirement for pre-term neonates., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Treating plantar warts is still a challenging problem with a long list of diverse treatment options that none of them seems to be definitive. To evaluate the effectiveness of intralesional acyclovir versus intralesional Hepatitis-B vaccine (HBV) in treatment of multiple resistant plantar warts. Forty-eight patients with resistant plantar warts completed the study with no dropouts. They were randomized into 3 groups; group(A) receiving intralesional HBV, group (B) receiving intralesional acyclovir and group (C) receiving intralesional saline as a control group over 5 biweekly sessions or until wart clearance. Clinical outcome was assessed through sequential digital lesion photographing upon each visit. Treatment related adverse reactions were recorded. 43.8%, 37.5% & 18.7% of Groups A, B &C respectively showed a complete response. pain was obvious in 100% and 56.3% of cases receiving intralesional acyclovir and HBV respectively. Up to the 6 month follow up period, none of the complete responders in all groups returned with a recurrence. Both acyclovir and HBV showed comparable efficacy and seem to be promising options for treating plantar warts being safe, affordable, and theoretically safe in immunocompromised cases., (© 2024. The Author(s).)

Objective: The goal of this clinical case is to report a case of ophthalmic zoster in a five-year-old boy and to insist on the relevance of early antiviral treatment (aciclovir) so as to minimize corneal affection and preserve visual function., Observation: We report the case of a five-year-old boy of preschool age with no notable pathological history who came for consultation with a painful eruption affecting the forehead, the upper eyelid, the nose. The clinical examination showed many erythematous vesicles affecting the left hemi-face. The diagnosis of ophthalmic zoster has been retained. Minimum biological laboratory assessment is normal. The treatment was local antiseptic and systemic aciclovir with high dose for ten days. The evolution was favorable. Zoster is rare in children. The ophthalmic form is exceptional. The diagnosis is clinical and should mention some bladdery lesions grouped in bunches with a disposition which follows a metamere. It can be responsible for serious ocular complications., Conclusion: The particularity of our observation is the presence of zoster in an immunocompetent child and the ophthalmic localization, that remains exceptional in children., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Herpes encephalitis, a rare yet potentially fatal viral infection, is treated exclusively with acyclovir, the sole antiviral medication used for this condition. Acyclovir recommended dose is 10 mg/kg/dose intravenous every 8 hours; however, it is unclear what body weight should be utilized in obese patients. Using the ideal body weight may result in subtherapeutic ineffective concentrations, while utilizing the actual body weight might result in acyclovir induced adverse effects, either nephrotoxicity or neurotoxicity or both., Objective: The objective of this scoping review is to explore existing evidence regarding acyclovir dosing for obese patients afflicted with herpes encephalitis., Methods: MEDLINE, EMBASE, Scopus, Web of Science, and CINAHL databases were searched on 26 May 2023, with no language restrictions. Two independent reviewers utilized the Covidence software to carry out the screening and selection of the articles. A total of 22 articles were included in the current review., Results: The prevalence of acyclovir-associated nephrotoxicity ranged from 13% to 21%, while the prevalence of neurotoxicity was not clearly defined. However, there is lack of evidence regarding what may arise from subtherapeutic concentrations. An approach has been suggested to help clinicians to give the most appropriate acyclovir dose to herpes encephalitis patients. Patients with normal kidney function could receive the normal doses based on actual weight if normal weight and based on adjusted body weight if obese. On the other hand, if the patients are experiencing augmented renal clearance, they could receive up to the maximum recommended doses., Conclusion: Overall, there is a lack of consistency on which body weight to use to calculate acyclovir dose in obese patients. So it is recommended that further studies compare the concentration of intravenous acyclovir between obese and nonobese patients and relating the resultant concentration with patient outcomes., Competing Interests: Disclosure The author declares no relevant conflicts of interest or financial relationships., (Copyright © 2024 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants (Loxodonta africana)., Animals: 15 African elephants (6 males and 9 females) of various ages., Methods: Famciclovir (15 mg/kg) was administered orally or per rectum once, with at least a three-week washout period between administrations. Blood was collected at 13 different timepoints per administration for 6 elephants, occurring between February and March 2020. An additional 9 elephants were sampled at variable timepoints per administration utilizing a sparse sampling design between July 2020 and January 2021. Plasma famciclovir and penciclovir levels were measured via HPLC and fluorescence detection. Pharmacokinetic analysis was completed in the summer of 2021 using noncompartmental analysis and nonlinear mixed-effects modeling., Results: Famciclovir was not detected in any sample, suggesting complete metabolism. Key pharmacokinetic parameters for penciclovir following oral administration were time to maximum concentration (tmax; 2.12 hours), area under the concentration-versus-time curve (AUC; 33.93 μg·h/mL), maximum observed concentration (Cmax; 3.73 μg/mL), and absorption half-life (t1/2; 0.65 hours). Following rectal administration, the values were: tmax, 0.65 hours; AUC, 15.62 μg·h/mL; Cmax, 2.52 μg/mL; and absorption t1/2, 0.13 hours., Conclusions: Famciclovir was rapidly metabolized to penciclovir. Oral administration resulted in slower absorption but higher maximum plasma concentration and higher AUC compared to rectal administration., Clinical Relevance: African elephants administered famciclovir via oral and rectal routes resulted in measurable serum penciclovir, and these findings may be utilized by clinicians treating viral infections in this species.

Introduction: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine whether antiviral therapy in HSV-positive patients improves outcome., Methods and Analysis: Prospective, multicentre, open-label, randomised, controlled trial in parallel-group design. Adult, mechanically ventilated patients with pneumonia and HSV type 1 detected in bronchoalveolar lavage (≥10 5 copies/mL) are eligible for participation and will be randomly allocated (1:1) to receive acyclovir (10 mg/kg body weight every 8 hours) for 10 days (or until discharge from the intensive care unit if earlier) or no intervention (control group). The primary outcome is mortality measured at day 30 after randomisation (primary endpoint) and will be analysed with Cox mixed-effects model. Secondary endpoints include ventilator-free and vasopressor-free days up to day 30. A total of 710 patients will be included in the trial., Ethics and Dissemination: The trial was approved by the responsible ethics committee and by Germany's Federal Institute for Drugs and Medical Devices. The clinical trial application was submitted under the new Clinical Trials Regulation through CTIS (The Clinical Trials Information System). In this process, only one ethics committee, whose name is unknown to the applicant, and Germany's Federal Institute for Drugs and Medical Devices are involved throughout the entire approval process. Results will be published in a journal indexed in MEDLINE and CTIS. With publication, de-identified, individual participant data will be made available to researchers., Trial Registration Number: NCT06134492., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This case report describes a pregnant patient with recent diagnosis of Human Immuno-Deficiency Virus (HIV) infection initiated on Anti-Retroviral Therapy (ART) in the second trimester, as well as high dose acyclovir high for large infected genital warts. She had no other HIV related opportunistic infections, and no prior anti tuberculosis treatment or preventive medication. Despite little response to acyclovir, patient was continuing on acyclovir for over 4 months. She subsequently developed recurrent anemia requiring frequent transfusion (14 units in total) over a 6-week period. On stopping acyclovir, the anemia subsided, a few weeks later she had a normal delivery, followed by surgical removal of the warts. At a follow-up 8 months later, she was well, with a healthy baby, and reported no other episodes of blood transfusion., Competing Interests: None declared., (© 2024 Nambuya M et al.)

Background: The treatment of warts is challenging and the development of an antiviral drug that can eradicate the human papilloma virus (HPV) is difficult. The viral origin of warts suggests that acyclovir, an antiviral drug with a proven efficacy in DNA viruses, may be a potential therapeutic option., Aim: To evaluate the efficacy and safety of intralesional acyclovir in the treatment of cutaneous warts., Methods: Thirty-one patients with cutaneous warts were allocated into 2 groups. Group A (19 patients) had intralesional acyclovir (70 mg/ml) injected into the warts, while group B (12 patients) received intralesional saline as control. The treatment was repeated at 2 week intervals until complete clearance or for a maximum of 5 sessions., Results: Complete clearance of warts was observed in 52.6%, partial response in 36.8%, and no response in 10.5% of the patients in the acyclovir group. Partial response was reported in 16.7%, and no response in 83.3% of the patients in the control group. A high statistically significant difference was found between the treatment and control groups ( P < .01). Adverse effects included pain during injection in 89.5%, blistering in 52.6% and erythema in5.3% of the patients. No recurrence was detected during the follow-up period., Conclusion: Intralesional acyclovir can be an effective and well-tolerated treatment modality for cutaneous warts.

Competing Interests: Competing interests: none declared.

In this work, series of pH-responsive hydrogels (FMA1-FMA9) were synthesized, characterized, and evaluated as potential carrier for oral delivery of an antiviral drug, acyclovir (ACV). Different proportions of β-cyclodextrin (β-CD), chitosan (CS), methacrylic acid (MAA) and N' N'-methylenebis-acrylamide (MBA) were used to fabricate hydrogels via free radical polymerization technique. Fourier transform infrared spectroscopy confirmed fabrication of new polymeric network, with successful incorporation of ACV. Scanning electron microscopy (SEM) indicated presence of slightly porous structure. Thermal analysis indicated enhanced thermal stability of polymeric network. Swelling studies were carried out at 37 °C in simulated gastric and intestinal fluids. The drug release data was found best fit to zero-order kinetics. The preliminary investigation of developed hydrogels showed a pH-dependent swelling behavior and drug release pattern. Acute oral toxicity study indicated no significant changes in behavioral, clinical, or histopathological parameters of Wistar rats. Pharmacokinetic study indicated that developed hydrogels caused a significant increase in oral bioavailability of ACV in rabbit plasma as compared to oral suspension when both were administered at a single oral dose of 20 mg kg -1 bodyweight. Hence, developed hydrogel formulation could be used as potential candidate for controlled drug delivery of an antiviral drug acyclovir.

Objective: The main goal of the present work was to develop and evaluate nanoemulsions (NEs) containing acyclovir (ACV) for ophthalmic drug delivery. Method: Firstly, component screening was performed by determining ACV solubility in various oils, surfactants, and co-surfactants. Different NE formulations were developed based on pseudo-ternary phase diagrams, and physicochemical assets were evaluated. Selected formulations were subjected to the drug release efficacy, stability studies, and ex-vivo trans-corneal permeation test. The safety of NEs was investigated by the modified Draize test and hen's egg test-chorioallantoic membrane (HET-CAM). Results: Based on the solubility studies, Tween 20, Triacetin, and Tramsectol ® P were chosen to prepare NE formulations. Developed NEs showed desirable physiochemical properties, including a droplet size of less than 15 nm. Selected formulations (F1 and F2) exhibited a sustained drug release pattern compared to the control group ( P < .001). ACV penetration from F1 and F2 to the excised bovine cornea was 2.85 and 2.9-fold more than the control, respectively. Furthermore, HET-CAM and modified Draize test confirmed that F1 and F2 were safe for ocular administration. Conclusion: Present investigation revealed that ACV-loaded NEs could be effective, and safe platform for ophthalmic delivery of ACV.

Treatment of herpes simplex infection requires high and frequent doses of oral acyclovir to attain its maximum therapeutic effect. The current therapeutic regimen of acyclovir is known to cause unwarranted dose-related adverse effects, including acute kidney injury. For this reason, a suitable delivery system for acyclovir was developed to improve the pharmacokinetic limitations and ultimately administer the drug at a lower dose and/or less frequently. In this study, solid lipid nanoparticles were designed to improve the oral bioavailability of acyclovir. The central composite design was applied to investigate the influence of the materials on the physicochemical properties of the solid lipid nanoparticles, and the optimized formulation was further characterized. Solid lipid nanoparticles formulated from Compritol 888 ATO resulted in a particle size of 108.67 ± 1.03 nm with an entrapment efficiency of 91.05 ± 0.75%. The analyses showed that the optimum combination of surfactant and solid lipid produced solid lipid nanoparticles of good quality with controlled release property and was stable at refrigerated and room temperature for at least 3 months. A five-fold increase in oral bioavailability of acyclovir-loaded solid lipid nanoparticles was observed in rats compared to commercial acyclovir suspension. This study has presented promising results that solid lipid nanoparticles could potentially be used as an oral drug delivery vehicle for acyclovir due to their excellent properties.

Previous evaluation of marketed acyclovir 5% creams using in vitro release testing (IVRT) and its correlation with the qualitative composition confirmed the discriminative characteristics of this methodology. This was in line with the principles of Topical drug Classification System (TCS). For the current research, experimental formulations were designed and prepared by applying controlled changes in manufacturing process, sources of raw materials, and amount of the excipients. The topical semisolids were representative for the four classes of TCS. The outcome of the IVRT and rheological assessments was evaluated in relation with the nature of the change and the functional role of the excipients. The variations in propylene glycol content from 5% to 40% impacted both the in vitro release rates (gradual decrease from 16.23 to 8.97 µg/cm 2 /min 0.5 ) and the microstructural characteristics (proportional increase of yield stress from 17.98 to 46.40 Pa). The inert excipients e.g. cetostearyl alcohol or white soft paraffin altered majorly the rheological behavior, as their functionality is mainly related to vehicle properties. IVRT was discriminative for the microstructural differences induced by both categories of excipients according to TCS dichotomy. This simple, reliable, and reproducible test reflected the impact of difference in quantitative composition and characteristics of excipients.

Purpose: To evaluate the long-term role of adherence to oral acyclovir prophylaxis in reducing the risk for recurrent herpes simplex virus keratitis (HSK) in children., Methods: A retrospective cohort study was performed including all pediatric patients 16 years or younger) with their first HSK diagnosis and treatment at our center. Children were started on a standardized oral acyclovir prophylactic regimen after the acute phase. Adherence to prophylaxis was assessed monthly through parent interviews. The possible association between any recurrence (not only the first) and exposure to acyclovir prophylaxis was evaluated using random-effects multivariate logistic regression., Results: A total of 20 eyes of 17 patients (8 boys and 9 girls) were included. The mean follow-up time was 3.5 years. Adherence to acyclovir prophylaxis was registered in 100% of patients with no recurrences and in 36.4% of patients with 1 or more recurrences (P = 0.035). All other tested variables (time of follow-up, sex, age, infectious diseases, underlying hematological diseases, eye, and HSK type) did not differ between the 2 groups. The multivariate model confirmed the lower risk for recurrence in patients who were compliant to therapy (adjusted odds ratio 0.04, 95% confidence intervals 0.00-0.42, P = 0.008). No adverse effects were recorded during follow-up., Conclusions: Oral acyclovir prophylaxis is a safe and an effective medical treatment for recurrent HSK and its long-term efficacy is associated with compliance to the therapy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of the low permeability across the gastrointestinal membrane. The use of nanoparticles of pseudoboehmite as a drug delivery system in vitro assays is a promising approach to further the permeability of acyclovir release. Here we report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles, using the sol-gel method, as a drug delivery system to improve the systemic bioavailability of acyclovir. The presence of pseudoboehmite nanoparticles were verified by infrared spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content by 4.6 times in the plasma of Wistar rats after 4 h administration. We determined that the toxicity of pseudoboehmite is low up to 10 mg/mL, in gel and the dried pseudoboehmite nanoparticles., (© 2021. The Author(s).)

In this study, two hydrophilic polymers hydroxypropyl methyl cellulose and beta-cyclodextrin (β-CD) are used to synthesize highly responsive and spongy polymeric matrices. Porous and stimulus-responsive polymeric network was developed to improve the solubility of acyclovir (ACV) at significant level. Grafting was successfully carried out by free radical polymerization technique. Spongy matrices were characterized by percentage entrapment efficiency, drug loading, solubility studies, FTIR, powder X-ray diffraction, TGA, DSC, XRD, SEM, swelling studies, and in vitro studies. Acute oral toxicity studies were conducted to determine the safety of oral administration of prepared HPMC-βCD-g-poly(AMPS) formulation. Porous and spongy structures were depicted in SEM images. Complex formation and thermal stability of constituents and drug (ACV) were analyzed by FTIR, TGA, and DSC spectra. XRD analysis revealed reduction in acyclovir crystallinity in spongy matrices. Particle size of optimized formulation was found in the range of 197 ± 2.55 nm. The momentous difference with reference product committed that drug solubility and release characteristics were markedly enhanced by the developed spongy matrices. Toxicity studies endorsed that developed spongy matrices were non-toxic and compatible to biological system. The efficient method of preparation, enhanced solubility, excellent physico-chemical characteristics, high dissolution, and non-toxic HPMC-βCD-g-poly(AMPS) spongy matrices may be a promising approach for oral delivery of poorly soluble drugs.

A 78-year-old woman was diagnosed with herpes zoster in the first branch of the trigeminal nerve and was treated with amenamevir. Subsequently, she was hospitalized for postherpetic neuralgia. Fever and unconsciousness were observed, and a diagnosis of varicella-zoster virus meningoencephalitis and vasculitis was made. In addition to the antithrombotic therapy, she was treated with intravenous acyclovir and steroid pulse therapy; however, her unconsciousness persisted. Amenamevir was not transferrable to the spinal fluid and resulted in an incomplete treatment of herpes zoster in the cerebral nerve region, suggesting that this case may be related to the severe course of the disease.

The objective of the study was to reinforce the applicability of the immersion cells for the in vitro release testing (IVRT) of topical formulations by using marketed acyclovir 5% cream formulation (Cream 1) as a model. The method employing the immersion cells was optimized by studying the effect of variables, such as membrane type, media temperature and volume, agitation speed, and cell size, on acyclovir release from the formulation. The in-house formulation similar to the qualitative and quantitative composition of Cream 1 and the other trial formulations with variable compositions were prepared and studied by using the immersion cells. Various other brands of acyclovir topical formulations available in the Indian market were also subjected to IVRT by using the optimized method. An increase in the media temperature from 32°C to 37°C and the stirring speed from 50 to 100 to 150 rpm led to an increase in the drug release. As the immersion cell size increased (0.5, 2 and 4 cm 2 surface area), the release rate also increased. Nitrocellulose membrane showed the highest drug release and Fluoropore ™ the least. The optimized IVRT method could establish the differences in the drug release rates among the formulations with the altered compositions. The method could also prove its discriminatory potential for various marketed formulations. The immersion cell method could serve as a simpler, facile, and reliable aid during product development and also as a quality control tool in assessing stability, aging, and batch-to-batch uniformity of semisolid formulations.

The channel catfish virus (CCV) can cause lethal hemorrhagic infection in channel catfish, resulting in significant economic losses in the fish industry. Effective drugs for the virus are still lacking. Acyclovir is known as a potent antiviral agent against human herpes viruses and some animal DNA viruses. The present study was undertaken to explore the antiviral response and mechanism of acyclovir against CCV in channel catfish ovary (CCO) cells. Acyclovir was able to significantly inhibit the expression of viral genes related to CCV viral DNA synthesis and suppress viral replication at a safe concentration. Furthermore, acyclovir blocked the cytopathic effects and apoptosis induced by CCV, thereby maintaining the normal cellular morphological structure, as shown by the protection of CCO cells from the formation of apoptotic bodies or nuclear fragmentation. Moreover, reverse transcript quantitative polymerase chain reaction (RT-qPCR) demonstrated that acyclovir suppressed the expression of caspase 3, caspase 8 and caspase 9, while there was no significant impact on the expression of the apoptosis-inhibiting gene bcl-2 in CCV-infected cells. In addition, acyclovir did not promote the expression of immune-related genes such as MyD88, Mx1, IRF3, IRF7, IFN-I, NF-kB and IL-1β, suggesting that the antiviral activity of acyclovir to CCV infection is not achieved by facilitating the expression of immune-related genes in CCO cells. Taken together, the results from this study suggest that acyclovir could effectively regulate CCV-induced infection, and thus is a promising therapeutic agent against CCV. Our results will aid our understanding of the pharmacological mechanisms of antiviral agents., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A 10-year-old boy underwent stem cell transplant for Hodgkin's lymphoma and developed vomiting and seizure in the postoperative period. An ophthalmic referral was made from intensive care unit, to rule out papilledema. On examination, there was no papilledema in both eyes, instead there were areas of retinal necrosis with no haemorrhages or vitritis in right eye. Cerebrospinal fluid serology was negative for herpes but MRI showed hyperintensity in temporal lobe. A clinical diagnosis of progressive outer retinal necrosis (PORN) was made and fundus picture was documented with help of a smartphone and 20D lens. High-dose intravenous injection acyclovir was started and PORN lesion improved on treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: None

A 72-year-old man was admitted to our hospital because of right facial muscle weakness and diplopia. He had been treated for aplastic anemia with cyclosporin for 2 years. Thirteen days before admission, a diagnosis of herpes zoster was made and treated with amenamevir. On admission, neurological examination revealed mild cognitive disturbance, mydriasis, weakness of the inferior rectus muscle of the left eye, and right peripheral facial nerve palsy. Cerebrospinal fluid (CSF) analysis showed elevated leukocytes and increased protein levels. Antibody index to varicella-zoster virus (VZV) was elevated in CSF to 25.6, although VZV DNA was negative by PCR. Head CT revealed multiple intracerebral hemorrhages in the left dorsal pons, left ventral midbrain, left thalamus, and left front-parietal lobe. MR angiography detected cerebral artery stenosis. In addition to intravenous acyclovir, the patient was treated with steroid pulse therapy and steroid tapering therapy. One month after admission, his symptoms improved. We diagnosed him with VZV vasculopathy. We believe that multiple intracerebral hemorrhages due to VZV vasculopathy caused facial and oculomotor nerve palsy. Our findings suggest that cerebral hemorrhage induced by VZV vasculopathy must be considered when differentiating cranial nerve palsy after herpes zoster.