brivudine and Recurrence

The overall incidence of herpes zoster in Europe is approximately 3 per 1000 people per year and more than 10 per 1000 people per year in those aged >80 years. Post herpetic neuralgia (PHN) is a common debilitating complication of herpes zoster, particularly in patients aged >50 years, in persons with severe pain or rash at presentation, and in those with significant prodromal symptoms. Antiviral drugs can effectively control acute symptoms and, if used early enough in the course of the illness, can help prevent the development of PHN and other complications. However, despite this, many patients do not receive such treatment. The economic impact of zoster and PHN is largely underestimated in Europe. Furthermore, there is considerable variation throughout Europe in the management of herpes zoster. Use of antiviral therapy including the newer potent antiviral agents such as brivudin, which requires less frequent administration than acyclovir, is improving patient outcomes in some European countries. However, in many countries, patient awareness of herpes zoster and, as a result, overall antiviral use is low. Guidelines recommending the use of antiviral agents, particularly in patients at risk of developing PHN, are available but are not widely used. More needs to be done to educate the general public and increase awareness among primary healthcare providers of the benefits of timely and appropriate pharmacological therapy in patients with herpes zoster.

Topics: Age Distribution; Aged; Aged, 80 and over; Antiviral Agents; Bromodeoxyuridine; Dose-Response Relationship, Drug; Drug Administration Schedule; Europe; Female; Herpes Zoster; Humans; Male; Middle Aged; Neuralgia, Postherpetic; Pain Measurement; Prognosis; Recurrence; Risk Assessment; Severity of Illness Index; Sex Distribution; Treatment Outcome

Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Genes, Viral; Guanine; Herpes Simplex; Humans; Mice; Recurrence; Simplexvirus; Thymidine Kinase; Virus Replication

Fifty patients with corneal dendritic ulceration were randomly entered into a double blind clinical trial comparing BVDU eyedrops with TFT eyedrops. Of those receiving TFT 100% healed in a mean time of 6.7 days, while 92% of those receiving BVDU healed in a mean time of 8.7 days. There was no statistical difference between the two groups in terms of numbers healed, but BVDU was significantly slower in terms of days to heal. After a mean follow-up period of 7.5 months there has been one recurrence in each group.

Topics: Administration, Topical; Adolescent; Adult; Aged; Antiviral Agents; Bromodeoxyuridine; Child; Corneal Ulcer; Double-Blind Method; Female; Follow-Up Studies; Humans; Keratitis, Dendritic; Male; Middle Aged; Prognosis; Recurrence; Trifluridine

A therapeutic trial with topical bromovinyldeoxyuridine (BVDU) plus low-dosage steroids was conducted in five patients with chronic zoster keratouveitis, who had previously received topical acyclovir (ACV) and steroids. In all cases, BVDU (plus steroids) was found to be superior to ACV (plus steroids). Yet BVDU was not able to keep the patients from having chronic relapsing varicella-zoster keratouveitis. This can probably be explained by pathophysiological reasons, i.e., the persistence and low-grade multiplication of the varicella-zoster virus in peripheral eye tissues during the chronic carrier stage. It is possible that this chronic carrier status could be obviated by vigorous antiviral treatment during the acute phase of the illness.

Topics: Administration, Topical; Adult; Bromodeoxyuridine; Chronic Disease; Clinical Trials as Topic; Dexamethasone; Drug Therapy, Combination; Female; Herpes Zoster Ophthalmicus; Humans; Keratitis; Male; Middle Aged; Ophthalmic Solutions; Pilot Projects; Recurrence; Uveitis

BVDU [(E)-5-(2-bromovinyl)-2'-deoxyuridine] has a potent and selective activity against herpes simplex (type 1) in both cell culture systems and animal models. The efficacy of topical BVDU treatment (0.1% eye drops) has been evaluated in 37 patients with different forms of herpes simplex keratitis. Of these patients, 35 were followed for 2-9 months (average 6.5 months). Most of the patients had first been treated with topical IDU (idoxuridine) or ara-A (adenine arabinoside), albeit unsuccessfully, before BVDU treatment was started. Upon BVDU treatment, dendritic corneal ulcers healed in 7.8 days (on average) and the geographic corneal ulcers in 10.8 days. BVDU also exerted a pronounced healing effect on stromal keratitis, whether it was used alone or in combination with topical corticosteroids. No early recurrences were observed. Late recurrences were seen in four patients who again responded quickly to BVDU treatment. No toxic side effects, whether local or systemic, were noted in any of the patients treated with BVDU. These results establish the efficacy of BVDU in the local treatment of herpetic keratitis in man.

Topics: Administration, Topical; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Bromodeoxyuridine; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Keratitis, Dendritic; Male; Middle Aged; Recurrence; Wound Healing

Two cases of acute retinal necrosis (ARN-) syndrome caused by an infection with varicella zoster virus (VZV) are demonstrated. VZV-DNA was detected in vitreous biopsies by polymerase-chain-reaction (PCR). The course of retinal necrosis was decisively improved by changing antiviral therapy from aciclovir and/or ganciclovir to brivudine.. Patient 1: 51 years, male, initial visual acuity 20/40; patient 2: 17 years, female, initial visual acuity 20/30. Both patients were immunocompetent and presented with an unilateral acute retinal necrosis syndrome with peripheral chorioretinitis, retinal vasculitis, vitreous inflammation and optic disc swelling, which resulted in progressive visual loss in a few days.. In both patients VZV-DNA was detected in vitreous biopsies with PCR. A regression of intraocular inflammation and necrotic retinal foci was only observed after changing the initial systemic therapy from aciclovir (Zovirax) intravenously 1500 mg/day) and/or ganciclovir (Cymeven) intravenously 250 mg/day) to brivudine (Zostex) per os 500 mg/day). Vitreoretinal surgery was necessary in both patients because of rhegmatogenous retinal detachment. Visual acuity stabilised in patient 1 to 20/200 and in patient 2 to 20/25 during a follow-up of 16 or 32 months, respectively.. Brivudine represents an alternative therapy, if standard treatment with aciclovir and/or ganciclovir failed in cases of ARN-syndrome due to presumed drug-resistant varicella zoster virus-subtypes. Complete remission and preservation of a satisfactory function can be achieved.

Topics: Acyclovir; Administration, Oral; Adolescent; Antiviral Agents; Bromodeoxyuridine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Ganciclovir; Herpes Zoster Ophthalmicus; Humans; Male; Middle Aged; Recurrence; Retinal Necrosis Syndrome, Acute; Retreatment; Treatment Failure

Patients suffering from dendritic and geographic corneal ulcers or herpetic stromal keratitis were treated with topical BVDU [(E)-5-(2-bromovinyl)-2'-deoxyuridine, bromovinyldeoxyuridine] 0.1% eyedrops administered during the day only at 1-hour intervals. Treatment with other antiviral drugs, i.e., idoxuridine, trifluridine, vidarabine or Zovirax had failed to ameliorate the ocular disease in 102 patients when their treatment was switched to BVDU eyedrops. Under BVDU therapy, dendritic keratitis in 44 patients healed within an average 7.8 days. Similarly, geographic corneal ulcers in 26 patients and stromal keratitis in 32 patients healed within an average period of 11.2 days and 30.7 days, respectively. Associated therapy with topical corticosteroids was stopped in 65 patients when the antiviral treatment was switched. However, topical corticosteroids had to be used together with BVDU drops to arrest stromal inflammation in 49 patients. Ultimately, 36 patients became corticosteroid-dependent. Except for local hypersensitivity reaction in three patients, BVDU eyedrops did not cause any toxic side effects.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Antiviral Agents; Bromodeoxyuridine; Child; Child, Preschool; Corneal Ulcer; Drug Resistance, Microbial; Female; Follow-Up Studies; Humans; Infant; Keratitis, Dendritic; Male; Middle Aged; Ophthalmic Solutions; Prognosis; Recurrence; Simplexvirus

Previous studies have shown that herpes simplex virus (HSV) type 2 (HSV-2) can be maintained in a latent state in a limited number of cells by elevating the incubation temperature after treatment of HSV-infected human fetus lung fibroblast cells with metabolic inhibitors. Superinfection with human cytomegalovirus (HCMV) of latently infected cells maintained at the elevated temperature reactivated latent virus. In addition, superinfection with temperature-sensitive mutants indicated that reactivation of latent HSV in vitro did not require the expression of late gene function(s) of the superinfecting virus. We now report the (i) design of an in vitro HSV-2-latency system in which a higher percentage of cells contain a virus genome that can be activated; and (ii) subsequent use of this system to further characterize the virus activation process. Superinfection with a transcription-negative temperature-sensitive mutant of HSV type 1 (HSV-1) did not reactivate HSV-2-replication, suggesting that adsorption and penetration of the superinfecting virus were not sufficient for reactivation of the latent virus. Furthermore, superinfection with HSV-1 in the presence of (E)-5-(2-bromovinyl)-2'-deoxyuridine did not reactivate HSV-2 replication, suggesting that the expression of the immediate-early gene products are not sufficient for HSV-2 reactivation. Collectively, these data suggest that in addition to the expression of immediate-early gene function(s) at least a subset of early HSV-1 gene products are required for reactivation of latent HSV-2 in vitro.

Topics: Antiviral Agents; Bromodeoxyuridine; Cell Line; Gene Expression Regulation; Genes, Viral; Humans; Mutation; Recurrence; Simplexvirus; Temperature; Virus Activation; Virus Replication

Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Herpes Simplex; Humans; Recurrence