Herpes simplex virus (HSV) infections in allogeneic haematopoietic stem cell transplantation (HSCT) recipients pose significant challenges, with higher incidence, severity, and risk of emergence of resistance to antivirals due to impaired T-cell mediated immunity. This literature review focuses on acyclovir-refractory/resistant HSV infections in HSCT recipients. The review addresses the efficacy of antiviral prophylaxis, the incidence of acyclovir-refractory/resistant HSV infections, and the identification of risk factors and potential prognostic impact associated with those infections. Additionally, alternative therapeutic options are discussed. While acyclovir prophylaxis demonstrates a significant benefit in reducing HSV infections in HSCT recipients and, in some cases, overall mortality, concerns arise about the emergence of drug-resistant HSV strains. Our systematic review reports a median incidence of acyclovir-resistant HSV infections of 16.1%, with an increasing trend in recent years. Despite limitations in available studies, potential risk factors of emergence of HSV resistance to acyclovir include human leucocyte antigen (HLA) mismatches, myeloid neoplasms and acute leukaemias, and graft-versus-host disease (GVHD). Limited evidences suggest a potentially poorer prognosis for allogeneic HSCT recipients with acyclovir-refractory/resistant HSV infection. Alternative therapeutic approaches, such as foscarnet, cidofovir, topical cidofovir, optimised acyclovir dosing, and helicase-primase inhibitors offer promising options but require further investigations. Overall, larger studies are needed to refine preventive and therapeutic strategies for acyclovir-refractory/resistant HSV infections in allogeneic HSCT recipients and to identify those at higher risk.

Mollaret\'s meningitis is a rare neurological disorder characterized by recurrent episodes of aseptic lymphocytic meningitis, often associated with herpes simplex virus 2 (HSV-2) infection. We report the case of a 39 y.o. Italian woman who experienced four episodes of aseptic lymphocytic meningitis between 2004 and 2023, diagnosed as Mollaret\'s meningitis. In each episode, the patient presented with fever, severe headache and photophobia. In two episodes cutaneous vesicles in the left gluteal area preceding meningitis symptoms were also reported. A diagnostic evaluation included a physical-chemical analysis and a real-time PCR of the cerebrospinal fluid (CSF). The CSF presented pleocytosis with lymphocytic predominance and a positive HSV-2 load, with a peak of 1234 copies/mL. The patient was treated successfully with acyclovir, and the symptoms resolved without neurological sequelae. This case highlights the importance of comprehensive diagnostic testing and vigilant monitoring to manage Mollaret\'s syndrome effectively.

Acute retinal necrosis is a rare but potentially devastating disease. Even in the era of modern medicine, retinal detachment is a frequent complication leading to vison loss, as well as phthisis bulbi. Whereas IV acyclovir still remains the standard of care, high doses of valacyclovir with/without additional intravitreal injections of foscarnet have been used. In an attempt to reduce the retinal detachment rate, prophylactic laser treatment and early vitrectomy have been proposed. In this article, we aim to review current diagnostic and treatment modalities.

UNASSIGNED: Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess the efficacy, safety, incidence of postherpetic neuralgia of brivudine.
UNASSIGNED: Data of randomized controlled Trials (RCTS) were obtained from the databases of both English (PubMed, Embase, and Cochrane Library) and Chinese (China National Knowledge Infrastructure, China Science Journal Database, and WanFang Database) literatures from inception to 12 September 2022. Meta-analyses of efficacy and safety of Brivudine for the treatment of herpes zoster for RCTS were conducted.
UNASSIGNED: The analyses included seven RCTS (2095 patients in experimental group and 2076 patients in control group) in the treatment of HZ with brivudine. It suggested that the brivudine group was superior to the control group in terms of efficacy (p = .0002) and incidence of postherpetic neuralgia (p = .04). But the incidence of adverse reactions has no significant difference between the brivudine and the control groups (p = .22). In addition, subgroup analysis of adverse events also showed that brivudine was about the same safety as other modalities in the treatment of HZ (p > .05).
UNASSIGNED: Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.

Epidemiological studies have shown that HPV-related diseases are the most prevalent sexually transmitted infections. In this context, this report will present various clinical cases demonstrating the effectiveness of Acyclovir (ACV) or its prodrug Valaciclovir (VCV), both acyclic guanosine analogs commonly used for the treatment of HHV-1 and HHV-2, for the treatment of HPV-related diseases. The report shows the remission of five cases of penile condyloma and a case of remission in a woman affected by cervical and vaginal condylomas and a vulvar giant condyloma acuminate of Buschke and Lowenstein. The literature review shows that ACV is effective in treating skin warts when administered orally, topically, and intralesionally, suggesting its therapeutic potential in other diseases associated with HPV. ACV was also used successfully as an adjuvant therapy for juvenile and adult forms of laryngeal papillomatosis, also known as recurrent respiratory papillomatosis, prolonging the patient\'s symptom-free periods. Although the prevention of HPV infections is certainly achieved with the HPV vaccine, ACV and VCV have shown to be effective even against genotypes not included in the current vaccine and can be helpful for those problematic clinical cases involving unvaccinated individuals, immunocompromised patients, people who live with HIV, or non-responders to the vaccine. We and others concluded that randomized clinical trials are necessary to determine the efficacy of ACV and VCV for HPV-related diseases.

Varicella-zoster virus (VZV), known for causing chickenpox, establishes latent infections in neural tissues. Reactivation of VZV can lead to herpes zoster (HZ) and various neurological complications. In this report, we present four cases of VZV meningitis and myelitis following amenamevir treatment for HZ dermatitis with positive VZV DNA in cerebrospinal fluid (CSF) revealed by polymerase chain reaction (PCR). Three of them were considered immunocompromised hosts given the fact that two of these patients were taking immunosuppressive drugs for rheumatoid arthritis, and one patient had a history of sigmoid colon cancer (four months after resection). After HZ onset, amenamevir, which has poor CSF transfer, was prescribed for all the patients, and all of them developed central nervous complications by VZV (meningitis in three cases and myelitis in one case) confirmed by PCR. All the patients were treated with acyclovir, which has a higher CSF transfer, and fully recovered. We speculate that amenamevir might have failed to prevent VZV infection in the central nervous system (CNS) and think that consideration should be given to administering acyclovir in preference to amenamevir for ΗΖ patients at high risk of CNS VZV infection, such as immunocompromised hosts.

OBJECTIVE: This study aimed to reveal the efficacy and safety of antivirals in patients with Ramsay Hunt syndrome.
METHODS: A literature search was conducted in PubMed, Ichushi-Web, and Cochrane Central Register of Controlled Trials. Published randomized controlled trials and observational studies, which compared antivirals versus placebo/no treatment for Ramsay Hunt syndrome, were included in the meta-analysis. The primary outcome was non-recovery at the end of the study follow-up. Data was analyzed using Review Manager Software, and pooled odds ratio (OR) with 95 % CI were calculated.
RESULTS: Two randomized controlled trials and 7 cohort studies met the eligible criteria, and 474 individuals were included in the meta-analysis. The OR of antivirals for non-recovery was 0.68 (95 % CI 0.37-1.27, p = 0.22). In subgroup analysis, the OR were 0.48 (95 % CI 0.15-1.61, p = 0.24) in patients with antivirals monotherapy and 0.73 (95 % CI 0.34-1.57, p = 0.42) in patients treated with combination therapy of antivirals and systematic corticosteroid.
CONCLUSIONS: This systematic review first shows the effectiveness of antivirals. Further study is needed to confirm the efficacy of antivirals.

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.

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.
CONCLUSIONS: 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.

UNASSIGNED: Acyclovir has an important role in the treatment of viral central nervous system (CNS) infection, especially herpes simplex virus (HSV)-1 encephalitis. It is therefore used broadly as empiric therapy for many patients who present to the hospital with symptoms of a possible neurologic infection. We sought to review our practices in acyclovir prescribing, deprescribing, and associated investigations for the clinical syndromes it treats.
UNASSIGNED: Through a retrospective chart review, we identified patients prescribed acyclovir for a possible CNS infection upon admission to Vancouver General Hospital between January 1, 2019, and December 31, 2019. Patient demographics, signs, symptoms, and comorbidities were taken from admission consultation notes or discharge summaries; their investigations, including laboratory tests and imaging, were also recorded. The primary purpose was to describe the appropriateness of empiric acyclovir use in suspected meningoencephalitis cases.
UNASSIGNED: Among the 108 patients treated with acyclovir, 94 patients had an indication for starting empiric treatment for encephalitis or meningitis. There was suspicion and workup for encephalitis alone in 76 patients. Among discharge diagnoses, the most common was delirium of a different identified source (18 cases), followed by unknown/other (15 cases). There were seven patients whose CSF viral PCR test was positive for HSV or varicella-zoster virus (VZV); three of them had HSV-1 encephalitis. There were two total adverse events recorded attributed to acyclovir; both cases were of mild acute kidney injury.
UNASSIGNED: We found that in many patients, acyclovir was not necessary or could have been stopped earlier, avoiding toxicity and drug costs.
UNASSIGNED: L’acyclovir joue un rôle important dans le traitement des infections virales du système nerveux central (SNC), notamment l’encéphalite herpétique. Il est donc largement utilisé comme traitement empirique auprès de nombreux patients qui consultent à l’hôpital à cause de symptômes d’éventuelle infection neurologique. Les chercheurs ont révisé leurs pratiques en matière de prescription et de déprescription d’acyclovir ainsi que les examens connexes de syndromes cliniques que traite ce médicament.
UNASSIGNED: Les chercheurs ont procédé à une analyse rétrospective des dossiers pour en extraire les patients à qui on avait prescrit de l’acyclovir à cause d’une éventuelle infection du SNC à leur admission au Vancouver General Hospital entre le 1er janvier et le 31 décembre 2019. Ils ont obtenu la démographie, les signes, les symptômes et les autres maladies des patients dans les notes de consultation à l’admission ou dans les résumés au congé. Ils ont également consigné les examens auxquels les patients ont été soumis, y compris les tests de laboratoire et d’imagerie. L’objectif primaire consistait à décrire le bien-fondé de l’utilisation empirique d’acyclovir en cas de soupçon de méningoencéphalite.
UNASSIGNED: Chez les 108 patients ayant reçu un traitement à l’acyclovir, 94 présentaient une indication de traitement empirique contre l’encéphalite ou la méningite. Les soupçons et le bilan d’encéphalite seule étaient observés chez 76 patients. Parmi les diagnostics au congé, les plus courants étaient un délire provenant d’une autre source (18 cas), suivi d’un diagnostic inconnu ou autre (15 cas). Chez sept patients, le test PCR du liquide céphalorachidien pour analyser le virus a donné un résultat positif au virus herpès simplex (VHS) ou au virus varicelle-zona, y compris trois cas d’encéphalite à VHS-1. Au total, deux événements indésirables attribués à l’acyclovir ont été consignés, tous deux de lésion rénale aiguë légère.
UNASSIGNED: Les chercheurs ont établi que l’aciclovir était inutile ou aurait pu être interrompu plus tôt chez de nombreux patients, ce qui aurait évité la toxicité et réduit les coûts de médicaments.