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Expert Review of Anti-infective Therapy Nov 2021: Acyclovir has led to the development of successful systemic therapy for herpes simplex virus and varicella-zoster virus (VZV) infection, and the use of valacyclovir... (Review)
Review
: Acyclovir has led to the development of successful systemic therapy for herpes simplex virus and varicella-zoster virus (VZV) infection, and the use of valacyclovir and famciclovir has improved treatment. Additionally, the use of a helicase-primase (HP) inhibitor (HPI), amenamevir, is changing the treatment of herpes zoster (HZ).: VZV infection is prevented by vaccines and is treated with antiviral agents. Acyclovir and penciclovir are phosphorylated by viral thymidine kinase and work as chain terminators. Improvements in the management of immunocompromised patients have reduced severe and prolonged immunosuppression and chronic VZV infection with acyclovir-resistant mutants has become rarer. The HP is involved in the initial step of DNA synthesis and amenamevir has novel mechanisms of action, efficacy to acyclovir-resistant mutants, and pharmacokinetic characteristics. The literature search for PUBMED was conducted on 10 April 2020 and updated on 4 November 2020.: Amenamevir has been used to treat HZ in Japan. Although the number of patients with VZV infection will decrease owing to the use of vaccines, the addition of HPI will improve treatment and treatment options for resistant viruses. The clinical use of HPIs in addition to current nucleoside analogs opens a new era of antiherpes therapy.
Topics: Acyclovir; Antiviral Agents; DNA Primase; Herpes Zoster; Herpesvirus 3, Human; Humans
PubMed: 33853490
DOI: 10.1080/14787210.2021.1917992 -
Ophthalmic Epidemiology Jun 2024Herpes stromal keratitis (HSK) is an immune-mediated corneal inflammation that occurs after a herpes simplex virus infection. This paper aims to systematically identify... (Review)
Review
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 ( < .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 ( < .001) and its control (prednisolone) groups ( = .002). A tacrolimus treatment group showed greater improvement in BCVA compared to its control (prednisolone) group ( < .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.
Topics: Humans; Keratitis, Herpetic; Antiviral Agents; Anti-Inflammatory Agents; Glucocorticoids; Acyclovir; Corneal Stroma
PubMed: 37184084
DOI: 10.1080/09286586.2023.2213324 -
Medwave Oct 2018Varicella (chickenpox) is a frequent and highly contagious infectious disease, caused by the Varicella zoster virus. Traditionally, it has been recommended to focus on... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Varicella (chickenpox) is a frequent and highly contagious infectious disease, caused by the Varicella zoster virus. Traditionally, it has been recommended to focus on the management of symptoms, since there is controversy about the role of antivirals, particularly in children and adolescents.
METHODS
To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.
RESULTS AND CONCLUSIONS
We identified three systematic reviews including three studies overall, all of them corresponding to randomized trials. We concluded the use of acyclovir might not decrease the associated complications, and it is not clear whether it reduces lesions or itching because the certainty of the evidence is very low.
Topics: Acyclovir; Adolescent; Antiviral Agents; Chickenpox; Child; Databases, Factual; Humans; Pruritus; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30339137
DOI: 10.5867/medwave.2018.06.7268 -
Molecules (Basel, Switzerland) Oct 2021Acyclovir (ACV) is an effective and selective antiviral drug, and the study of its toxicology and the use of appropriate detection techniques to control its toxicity at... (Review)
Review
Acyclovir (ACV) is an effective and selective antiviral drug, and the study of its toxicology and the use of appropriate detection techniques to control its toxicity at safe levels are extremely important for medicine efforts and human health. This review discusses the mechanism driving ACV's ability to inhibit viral coding, starting from its development and pharmacology. A comprehensive summary of the existing preparation methods and synthetic materials, such as 5-aminoimidazole-4-carboxamide, guanine and its derivatives, and other purine derivatives, is presented to elucidate the preparation of ACV in detail. In addition, it presents valuable analytical procedures for the toxicological studies of ACV, which are essential for human use and dosing. Analytical methods, including spectrophotometry, high performance liquid chromatography (HPLC), liquid chromatography/tandem mass spectrometry (LC-MS/MS), electrochemical sensors, molecularly imprinted polymers (MIPs), and flow injection-chemiluminescence (FI-CL) are also highlighted. A brief description of the characteristics of each of these methods is also presented. Finally, insight is provided for the development of ACV to drive further innovation of ACV in pharmaceutical applications. This review provides a comprehensive summary of the past life and future challenges of ACV.
Topics: Acyclovir; Antiviral Agents; Humans; Molecular Structure
PubMed: 34770975
DOI: 10.3390/molecules26216566 -
Indian Pediatrics Sep 2014
Topics: Acyclovir; Antiviral Agents; Child; Female; Humans; Lip; Stomatitis, Herpetic; Tongue
PubMed: 25228626
DOI: No ID Found -
Polish Journal of Veterinary Sciences Dec 2023Feline herpesvirus-1 (FHV-1) can cause lifelong problems such as rhinotracheitis and ocular disease due to latency and reactivation in affected cats. The particular...
Feline herpesvirus-1 (FHV-1) can cause lifelong problems such as rhinotracheitis and ocular disease due to latency and reactivation in affected cats. The particular effects of antiviral drugs have been separately investigated in previous studies for decades and little is known about the combination treatment in active FHV-1 infection. Therefore, we aimed to evaluate the effects of antiviral combination on clinical effectiveness in cats with naturally occurring FHV-1 infection. 28 cats suffering from clinical signs of sneezing, nasal congestion, conjunctivitis, and eye/nose discharge were involved in this study following FHV-1 DNA detection by PCR assay in oculo-oropharyngeal samples. The treatment protocol was as follows: oral famciclovir and L-lysine, ophthalmic acyclovir, and subcutaneous amoxicillin plus clavulanic acid. The symptoms improved each day and total recovery success rate was 80% reduction in clinical scores at the end of the treatment on day 10 (p<0.001). Additionally, PCR was found to be negative for FHV-1 DNA in 82.1% of the samples after the treatment. There were mild decreases in neutrophil and monocyte counts (p>0.05). The arginine to lysine ratio decreased in favour of lysine (p<0.01). As a result, the antiviral combination treatment with famciclovir, L-lysine and ophthalmic acyclovir, and antibacterial drug appears to be clinically effective for the treatment of naturally occurring active FHV-1 infection in cats. In addition, any adverse clinical effect has not been determined associated with the antiviral combination during the study.
Topics: Cats; Animals; Famciclovir; Antiviral Agents; Lysine; Herpesviridae Infections; Acyclovir; Varicellovirus; DNA; Cat Diseases
PubMed: 38088482
DOI: 10.24425/pjvs.2023.148290 -
Journal of Clinical Virology : the... Oct 2023Antiviral resistance in human herpes simplex viruses (HSV) remains a significant clinical challenge in immunocompromised populations. Although molecular tests have...
BACKGROUND
Antiviral resistance in human herpes simplex viruses (HSV) remains a significant clinical challenge in immunocompromised populations. Although molecular tests have largely replaced viral culture for HSV diagnosis and molecular antiviral resistance testing is available for many viruses, HSV resistance testing continues to rely on phenotypic, viral culture-based methods, requiring weeks for results. Consequently, treatment of suspected HSV resistance remains largely empiric.
METHODS
We used HSV whole genome sequencing and a database of previously characterized HSV acyclovir and foscarnet resistance mutations to evaluate the performance of genotypic antiviral resistance testing among 19 control strains compared to in-house plaque reduction assay (PRA) and 25 clinical isolates sent for reference lab PRA antiviral resistance testing.
RESULTS
Among control strains, 23/29 (79.3%) results were concordant, 5 (17.2%) were indeterminate, and 1 (3.4%) was discordant. Indeterminate results were caused by variants of uncertain significance (VUS), including mutations without published phenotypes and mutations with contradictory results. Among clinical isolates, 14/40 (35%) results were concordant, 17 (42.5%) were indeterminate, and 9 (22.5%) were discordant. All discordant results were in reportedly phenotypically-susceptible HSV-1 strains yet possessed resistance mutations. Three contained resistant subpopulations. 6/8 (75%) discordant phenotypes were concordant with resistant genotypes upon repeat PRA.
CONCLUSIONS
These data support the combination of genotypic and phenotypic testing to diagnose HSV resistance more accurately and likely more rapidly than phenotypic testing alone. Genotypic context of resistance mutations and the ability of viral strains to form plaques in culture may affect phenotypic resistance results, highlighting the limitations of PRA alone as a gold standard method.
Topics: Humans; Antiviral Agents; Herpesvirus 2, Human; Acyclovir; Foscarnet; Herpesvirus 1, Human; Genotype; Drug Resistance, Viral; Herpes Simplex
PubMed: 37586184
DOI: 10.1016/j.jcv.2023.105554 -
Revista de Neurologia Apr 2022The SARS-CoV-2 virus, which causes COVID-19, could give rise to damage the nervous system. Many studies have been conducted on this topic, but few have focused...
INTRODUCTION
The SARS-CoV-2 virus, which causes COVID-19, could give rise to damage the nervous system. Many studies have been conducted on this topic, but few have focused specifically on encephalitis. The effect of SARS-CoV-2 on the clinical expression of other neurotropic viruses, such as Herpesviridae, is unknown.
CASE REPORTS
We describe the cases of two young men (39 and 18 years old) in whom SARS-CoV-2 had been detected -reverse transcription polymerase chain reaction (RT-PCR)-, and with a clinical diagnosis and cerebrospinal fluid (CSF) analysis consistent with encephalitis. The first patient had a positive PCR for varicella zoster virus in CSF, while the second had a positive PCR for herpes simplex virus types 1 and 2. The first patient, who was recently diagnosed with human immunodeficiency virus, presented with fever, headache, vomiting, cough, inappropriate behaviour and epileptic seizures; the second was seen to have fever, headache, myalgia and exanthema. Both offered the same laboratory findings (lymphopenia and high interleukin 6). CSF showed pleocytosis with a predominance of monomorphonuclear cells, hyperproteinorrachia and normal glycorrhachia. A cranial CT scan showed only mild diffuse cerebral oedema in the first case. Both cases were treated with corticosteroids, antibiotics and acyclovir. The second progressed favourably, while the first did not.
CONCLUSIONS
Little is known about co-infection of SARS-CoV-2 with neurotropic viruses, such as Herpesviridae, and we have only limited evidence of direct neurological involvement of SARS-CoV-2, due to the technical difficulty of detecting it in the nervous system, thus making it important to take co-infection into account in order to be able to establish an early diagnosis and treatment to improve prognosis.
Topics: Acyclovir; COVID-19; Encephalitis; Herpesvirus 3, Human; Humans; Male; SARS-CoV-2
PubMed: 35383876
DOI: 10.33588/rn.7408.2021121 -
Journal of Medical Virology Jul 2016Cytomegalovirus (CMV) continues to be a leading cause of morbidity and mortality in transplant recipients, despite major advancements in preventative strategies.... (Review)
Review
Cytomegalovirus (CMV) continues to be a leading cause of morbidity and mortality in transplant recipients, despite major advancements in preventative strategies. Antiviral prophylaxis and pre-emptive antiviral therapeutic regimens are associated with a high incidence of late-onset end-organ disease and cause drug-related toxicity when overused. Therefore, the identification of risk factors for CMV replication is required. Genetic and immunological factors that predispose individuals to CMV-related clinical complications have been identified and may be instrumental for optimizing CMV treatment in the future. Evidence suggests a causal pathogenetic link between CMV-related complications and inflammatory diseases in non-canonically immunosuppressed individuals such as patients with lung injury and critically ill and cancer patients. However, a randomized clinical trial is required to determine if a causal relationship exists.
Topics: Acyclovir; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Immunocompromised Host; Risk Factors; Transplant Recipients
PubMed: 26681168
DOI: 10.1002/jmv.24450 -
Drug Delivery 2016Viral and fungal cutaneous manifestations are regularly encountered in immunocompromised human immunodeficiency virus/acquired immunodeficiency syndrome individuals and... (Comparative Study)
Comparative Study
CONTEXT
Viral and fungal cutaneous manifestations are regularly encountered in immunocompromised human immunodeficiency virus/acquired immunodeficiency syndrome individuals and can be treated by drugs such as acyclovir and ketoconazole, respectively.
OBJECTIVE
The aim of this study was to determine whether the novel Pheroid delivery system improved the transdermal delivery and/or dermal delivery of acyclovir and ketoconazole when incorporated into semi-solid formulations.
MATERIALS AND METHODS
Semi-solid products (creams and emulgels) containing these drug compounds were formulated, either with or without (control) the Pheroid delivery system. The stability of the formulated semi-solid products was examined over a period of six months and included the assay of the actives, pH, viscosity, mass loss and particle size observation. Vertical Franz cell diffusion studies and tape stripping methods were used to determine the in vitro, stratum corneum (SC)-epidermis and epidermis-dermis delivery of these formulations.
RESULTS AND DISCUSSION
Stability tests showed that none of the formulations were completely stable. Acyclovir showed a biphasic character during the in vitro skin diffusion studies for all the tested formulations. The Pheroid™ cream enhanced the transdermal, SC-epidermis and epidermis-dermis delivery of acyclovir the most. The average amount of ketoconazole diffused over 12 h showed improved delivery of ketoconazole, with the Pheroid™ emulgel exhibiting the best transdermal and epidermis-dermis delivery.
CONCLUSION
The Pheroid formulae increased transdermal penetration as well as delivery to the dermal and epidermal skin layers. The Pheroid emulgel and the Pheroid cream increased the topical delivery of ketoconazole and acyclovir, respectively.
Topics: Acyclovir; Administration, Cutaneous; Antifungal Agents; Antiviral Agents; Diffusion; Drug Carriers; Drug Compounding; Drug Stability; Drug Storage; Fatty Acids; Female; Gels; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Ketoconazole; Nitrous Oxide; Ointments; Particle Size; Skin; Skin Absorption; Solubility; Technology, Pharmaceutical; Viscosity
PubMed: 25005585
DOI: 10.3109/10717544.2014.933283