M2 Genotype of Varicella zoster virus associated with Severe Herpes zoster in Pakistan.

This case report is of herpes zoster which is caused by Varicella zoster virus (VZV). The patient was presented with acute renal failure associated with intravenous acyclovir administration for its management. A 50 years old man visited the hospital with rashes on his back. The serum sample was positive for anti-VZV IgM via Enzyme Linked Immunosorbent Assay (ELISA), and vesicular swab for VZV via polymerase chain reaction (PCR). Phylogenetic analysis identified it as M2-genotype. Patient was treated with intravenous acyclovir administration, which led to acute renal failure. Later with shift to oral acyclovir, renal functions were restored. Elderly patients with reactivation of VZV in Pakistan are at risk to contract herpes zoster. Acyclovir is drug of choice via intravenous route was found to be nephrotoxic, however oral acyclovir was safe and effective. This is first report on pathogenic VZV genotype from Pakistan and is presented to highlight that the herpes zoster cases of elderly patients' treatment option need to be revisited.

New Insights Into the Therapeutic Management of Varicella Zoster Virus Meningitis: A Series of 123 Polymerase Chain Reaction-Confirmed Cases.

Background: Varicella zoster virus (VZV) can reactivate and cause meningitis, but few studies have distinguished it from meningoencephalitis regarding treatment recommendations.The objective of this study was to assess the outcomes of a large series of patients with VZV meningitis according to their therapeutic management. Methods: We conducted a bicentric retrospective cohort study, in Paris, France, including all adult patients with a cerebrospinal fluid sample positive for VZV by polymerase chain reaction between April 2014 and June 2022. We distinguished meningitis from encephalitis according to the International Encephalitis Consortium criteria. Unfavorable outcome was defined as mortality or functional sequelae defined by a loss of 2 points on the modified Rankin Scale. Results: We included 123 patients with meningitis. Among them, 14% received no antivirals, while 20% were treated with oral valacyclovir alone, 41% with a short course of intravenous (IV) acyclovir before switch to valacyclovir, and 25% with a long course of IV acyclovir. Outcomes were favorable regardless of antiviral regimen. In multivariate analysis, only age, underlying immunosuppression, and cranial radiculitis appear to be predictive factors for longer IV therapy, based on the Akaike information criterion. Conclusions: In this study, patients with VZV meningitis had a good outcome, with no evidence of any impact of the treatment strategy. However, further studies are needed to support the possibility of milder treatment in immunocompetent patients, avoiding cost and side effects of IV acyclovir.

A case report: recurrent anemia related to long term acyclovir use in a pregnant HIV infected Ugandan.

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.

Acyclovir as a Novel Treatment for Severe Chronic Active Epstein-Barr Virus.

Epstein-Barr virus (EBV) is a widely infectious pathogen affecting most of the global population at some point in their life. While, typically, primary infections are subclinical, chronic persistence of the virus due to T-cell proliferation can cause severe complications. Acute hepatitis due to chronic active EBV (CAEBV) has rarely been documented. This case details a previously healthy 81-year-old woman who presented with complaints of diffuse abdominal pain, nausea, and vomiting. Her diagnostic workup demonstrated an EBV infection with worsening thrombocytopenia, transaminitis, and hepatocellular liver injury with acute ascites. Her hospitalization was resistant to the traditional supportive treatment of EBV, requiring intensive care management and unorthodox therapy. Although antivirals have demonstrated limited utility in the treatment of CAEBV, the severity of her illness and refractory hospital course necessitated the use of acyclovir. She made a complete recovery with no deficits. The case demonstrates the presentation of acute hepatitis and ascites as a result of CAEBV, the clinical sequelae, and acyclovir as a potential new treatment option.

ACV with/without IVM: a new talk on intestinal CDX2 and muscular CD34 and Cyclin D1 during Trichinella spiralis infection.

The current study assessed the efficacy of Acyclovir (ACV) and Ivermectin (IVM) as monotherapies and combined treatments for intestinal and muscular stages of Trichinella spiralis infection. One-hundred Swiss albino mice received orally 250 ± 50 infectious larvae and were divided into infected-untreated (Group-1), IVM-treated (Group-2), ACV-treated (Group-3), combined IVM+ACV (Group-4), and healthy controls (Group-5). Each group was subdivided into subgroup-A-enteric phase (10 mice, sacrificed day-7 p.i.) and subgroup-B-muscular phase (10 mice, sacrificed day-35 p.i.). Survival rate and body weight were recorded. Parasite burden and intestinal histopathology were assessed. In addition, immunohistochemical expression of epithelial CDX2 in the intestinal phase and CyclinD1 as well as CD34 in the muscular phase were evaluated. Compared, IVM and ACV monotherapies showed insignificant differences in the amelioration of enteric histopathology, except for lymphocytic counts. In the muscle phase, monotherapies showed variable disruptions in the encapsulated larvae. Compared with monotherapies, the combined treatment performed relatively better improvement of intestinal inflammation and reduction in the enteric and muscular parasite burden. CDX2 and CyclinD1 positively correlated with intestinal inflammation and parasite burden, while CD34 showed a negative correlation. CDX2 positively correlated with CyclinD1. CD34 negatively correlated with CDX2 and CyclinD1. IVM +ACV significantly ameliorated CDX2, CyclinD1, and CD34 expressions compared with monotherapies. Conclusion. T. spiralis infection-associated inflammation induced CDX2 and CyclinD1 expressions, whereas CD34 was reduced. The molecular tumorigenic effect of the nematode remains questionable. Nevertheless, IVM +ACV appeared to be a promising anthelminthic anti-inflammatory combination that, in parallel, rectified CDX2, CyclinD1, and CD34 expressions.

Herpes Simplex Virus (HSV)-Induced Erythema Multiforme: A Rare Case Report.

A polymorphous recurrent eruption mostly composed of macules, bullae, papules, and target lesions, which are often distributed symmetrically and can spread to distant extremities, and oral mucosae are the features associated with erythema multiforme (EM). Herpes simplex virus (HSV) is a common condition that is associated with EM and manifests in late adulthood. It shows recurrence and is usually diagnosed clinically. Following is a case of HSV-associated EM. A 45-year-old patient visited the outpatient department with complaints of oral ulceration and associated pain and burning sensation. The patient also reported that similar ulcers were seen two months prior to her visit, which resolved on their own and the recurrence was seen two days prior to the visit. The recurrence occurred with more severity of pain and inflammation as compared to previous ulcers. The patient was kept on a combination therapy of antivirals, steroids, silymarin, and multivitamins for four visits with a tapering dose of steroids. Post-treatment, there was no recurrence till date and the patient is able to perform mastication as well as deglutition without any pain or burning sensation.

Trilayered nanocellulose-based patches loaded with acyclovir and hyaluronic acid for treatment of herpetic lesions.

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 (ACVT) or divided between two layers (ACVH), 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 ACVH patch (77 ±â€¯5 %, 10 min) than from the ACVT one (50 ±â€¯7 %), suggesting efficient drug delivery. ACVH closely resembled a commercial cream formulation in 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.

Nonsexual Genital Ulcers Secondary to Epstein-Barr Virus in a Pediatric Patient.

This case report focuses on a rare presentation of Epstein-Barr virus as genital ulcers in a 14-year-old girl with no sexual activity history. Despite initial misdiagnosis and failed acyclovir treatment, investigations ruled out sexually transmitted causes but revealed elevated Epstein-Barr virus antibodies. Subsequent treatment with a 14-day prednisone course led to significant improvement. This case emphasizes the importance of considering nonsexual etiologies for genital ulcers to prevent delayed or inappropriate treatment and highlights the need for broader education on such atypical presentations.

Intralesional acyclovir versus intralesional Hepatitis-B vaccine in treatment of resistant plantar warts: a randomized controlled trial.

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.

CRISPR/Cas9-mediated genome editing of the thymidine kinase gene in a clinical HSV-1 isolate identifies F289S as novel acyclovir-resistant mutation.

Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that establishes a lifelong infection in sensory neurons of infected individuals, accompanied with intermittent reactivation of latent virus causing (a)symptomatic virus shedding. Whereas acyclovir (ACV) is a safe and highly effective antiviral to treat HSV-1 infections, long-term usage can lead to emergence of ACV resistant (ACVR) HSV-1 and subsequently ACV refractory disease. Here, we isolated an HSV-1 strain from a patient with reactivated herpetic eye disease that did not respond to ACV treatment. The isolate carried a novel non-synonymous F289S mutation in the viral UL23 gene encoding the thymidine kinase (TK) protein. Because ACV needs conversion by viral TK and subsequently cellular kinases to inhibit HSV-1 replication, the UL23 gene is commonly mutated in ACVR HSV-1 strains. The potential role of the F289S mutation causing ACVR was investigated using CRISPR/Cas9-mediated HSV-1 genome editing. Reverting the F289S mutation in the original clinical isolate to the wild-type sequence S289F resulted in an ACV-sensitive (ACVS) phenotype, and introduction of the F289S substitution in an ACVS HSV-1 reference strain led to an ACVR phenotype. In summary, we identified a new HSV-1 TK mutation in the eye of a patient with ACV refractory herpetic eye disease, which was identified as the causative ACVR mutation with the aid of CRISPR/Cas9-mediated genome engineering technology. Direct editing of clinical HSV-1 isolates by CRISPR/Cas9 is a powerful strategy to assess whether single residue substitutions are causative to a clinical ACVR phenotype.

Acyclovir treatment of varicella-zoster virus meningeal infections and acute kidney injury: a multicentre case series study.

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.

Herpes simplex (HSV-1) encephalitis in an infant: a case report study.

Introduction and importance: The herpes simplex virus (HSV) is the most common cause of acute sporadic encephalitis, a severe and often fatal disease in humans. It is associated with high mortality and morbidity rates in untreated patients. Case presentation: An 11-month-old child was admitted to the hospital presenting with acute fever and seizures characterized by staring episodes and spastic movements affecting the left side of the body. Diagnostic workup revealed abnormal T2 flair hyperintense foci in bi-temporoparietal lobes and right thalamus, and bilateral otomastoiditis were detected. A positive result for HSV-1 was obtained through HSV type 1/2 polymerase chain reaction (PCR) testing, leading to a diagnosis of herpes encephalitis. Clinical discussion: While acyclovir has proven to be an effective therapeutic option, mortality and neurological sequelae continue to be reported in a notable fraction of patients. HSV encephalitis is mainly caused by two strains of the herpes simplex virus: HSV-1, more frequently observed in children and adults, and HSV-2, commonly seen in neonates and those with compromised immune systems. MRI scans often reveal that the brain lesions are localized to certain areas, although temporal involvement may not always be evident. The symptoms of herpetic encephalitis can greatly vary, making early diagnosis and treatment vital for improving patient outcomes. Conclusion: This case report highlights the clinical presentation, diagnostic challenges, and treatment strategies for HSV-1 encephalitis and underscores the importance of early recognition and prompt initiation of antiviral therapy in suspected cases of HSV-1 encephalitis.

Acyclovir extravasation in a newborn: a case report.

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.

Successful treatment of acyclovir-resistant herpes simplex virus infection with amenamevir in a patient who received umbilical cord blood transplantation for T-cell prolymphocytic leukemia.

A 34-year-old woman received umbilical cord blood transplantation for refractory T-cell prolymphocytic leukemia after salvage therapy with alemtuzumab. She developed right angular cheilitis on the 46th day after transplantation, which worsened after receiving systemic steroid therapy for extensive chronic graft versus host disease. The treatment dosage of acyclovir (ACV), ganciclovir, and vidarabine ointment was not effective due to ACV-resistant mutations of the herpes simplex virus type 1 (HSV-1) in the thymidine kinase domain. Foscarnet is expected to be effective against ACV-resistant HSV-1 infection. However, it could not be used because the patient developed renal dysfunction. Several viral thymidine kinase mutations related to ACV resistance were found in the patient's sample. Nevertheless, amenamevir, a helicase-primase complex inhibitor, was effective in our patient who was significantly immunocompromised after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ACV-resistant HSV infection after allo-HSCT is an rare but important complication in the era of low-dose long-term ACV prophylaxis. To date, there is no established treatment against ACV-resistant HSV infection. This case report showed that amenamevir could be a promising treatment option for ACV-resistant HSV infection in patients with renal failure after allo-HSCT.

Varicella-Zoster Virus Reactivation After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation, Single-Center Experience of Acyclovir Prophylaxis.

BACKGROUND: Varicella-zoster virus (VZV) reactivation is the most common infectious complication in the late posthematopoietic stem cell transplantation (HSCT) period and is reported as 16%-41%. Acyclovir prophylaxis is recommended for at least 1 year after HSCT to prevent VZV infections. However, studies on the most appropriate prophylaxis are ongoing in pediatric patients. METHODS: Patients who underwent allogeneic HSCT between January 1, 1996 and January 1, 2020 were retrospectively analyzed to outline the characteristics of VZV reactivation after allogeneic HSCT in pediatric patients using 6 months acyclovir prophylaxis. RESULTS: There were 260 patients and 273 HSCTs. Median age was 10.43 (0.47-18.38), and 56% was male. Median follow-up was 2325 days (18-7579 days). VZV reactivation occurred in 21.2% (n = 58) at a median of 354 (55-3433) days post-HSCT. The peak incidence was 6-12 months post-HSCT (43.1%). Older age at HSCT, female gender, history of varicella infection, lack of varicella vaccination, low lymphocyte, CD4 count, and CD4/CD8 ratio at 9 and 12 months post-HSCT was found as a significant risk for herpes zoster (HZ) in univariate analysis, whereas history of varicella infection and low CD4/CD8 ratio at 12 months post-HSCT was an independent risk factor in multivariate analysis. CONCLUSIONS: Tailoring acyclovir prophylaxis according to pre-HCT varicella history, posttransplant CD4 T lymphocyte counts and functions, and ongoing immunosuppression may help to reduce HZ-related morbidity and mortality.

Computational analysis of antiviral drugs using topological descriptors.

Many health challenges are attributed to viral infections, which represent significant concerns in public health. Among these infections, diseases such as herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV) infections have garnered attention due to their prevalence and impact on human health. There are specific antiviral medications available for the treatment of these viral infections. Drugs like Cidofovir, Valacyclovir, and Acyclovir are commonly prescribed. These antiviral drugs are known for their efficacy against herpesviruses and related viral infections, leveraging their ability to inhibit viral DNA polymerase. A molecular descriptor is a numerical value that correlates with specific physicochemical properties of a molecular graph. This article explores the calculation of distance-based topological descriptors, including the Trinajstic, Mostar, Szeged, and PI descriptors for the aforementioned antiviral drugs. These descriptors provide insights into these drugs' structural and physicochemical characteristics, aiding in understanding their mechanism of action and the development of new therapeutic agents.

A new compound, phomaherbarine A, induces cytolytic reactivation in epstein-barr virus-positive B cell lines.

Epstein-Barr virus (EBV), the first virus found to induce cancer in humans, has been frequently detected in various types of B cell lymphomas. During its latent phase, EBV expresses a limited set of proteins crucial for its persistence. Induction of the lytic phase of EBV has shown promise in the treatment of EBV-associated malignancies. The present study assessed the ability of phomaherbarine A, a novel compound derived from the endophytic fungus Phoma herbarum DBE-M1, to stimulate lytic replication of EBV in B95-8 cells. Phomaherbarine A was found to efficiently initiate the expression of both early and late EBV lytic genes in B95-8 cells, with this initiation being further heightened by the addition of phorbol myristate acetate and sodium butyrate. Moreover, phomaherbarine A demonstrated notable cytotoxicity against the EBV-associated B cell lymphoma cell lines B95-8 and Raji. Mechanistically, phomaherbarine A induces apoptosis in these cells through the activation of caspase-3/7. When combined with ganciclovir, phomaherbarine A does not interfere with the reduction of viral replication by ganciclovir and sustains its apoptosis induction. In conclusion, these findings indicate that phomaherbarine A may be a promising candidate for therapeutic intervention in patients with EBV-associated B cell lymphomas.

Polysilsesquioxane decorated ZIF-8 as a potential pH-responsive vehicle for topical delivery and release of acyclovir and tetracycline: Investigation of blood compatibility, cytotoxicity and antibacterial properties.

In this research, poly-chloropropylmethyl-silsesquioxanen was prepared and decorated with ZIF-8 in order to investigate its loading capacity for acyclovir and tetracycline. Before and after drug loadings, the composites were characterized by FT-IR, SEM-EDS, XRD, and XPS analyses. Then, the in-vitro release of these drugs was investigated by UV-Vis spectroscopy in different buffers (pH = 5, 7.4, and 9.1). The results showed that the release of ACV reached a maximum amount of 41.3 mg at pH = 7.4 during 12 h. In comparison, the release of TC reached a maximum amount of 22.5 mg at pH = 5 during 6 h. The blood compatibility, in-vitro cytotoxicity on the L929 fibroblast cells line, and antibacterial assay against Staphylococcus aureus and Pseudomonas aeruginosa were also investigated for this composite as a drug carrier.

Efficacy and safety of brivudine for the treatment of herpes zoster: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.

Remission of HPV-Related Diseases by Antivirals for Herpesvirus: Clinical Cases and a Literature Review.

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.