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PubMed2006

Genital herpes: antiviral therapy for symptom relief and prevention of transmission.

The episodic and daily suppressive treatment of genital herpes is safe and effective with the currently available antiviral agents: acyclovir, valacyclovir and famciclovir. Clinical strategies for the comprehensive management of genital herpes simplex virus infections are recommended. Data from recent clinical trials demonstrating the efficacy of shorter duration of therapy for recurrences and the use of antivirals for the prevention of transmission are reviewed in this article. The factors influencing the choice of therapy, such as cost, ease of dosing and acyclovir resistance are also discussed.

2-Aminopurine↗
PubMed2001

Varicella in a pediatric heart transplant population on nonsteroid maintenance immunosuppression.

OBJECTIVE: Varicella-zoster virus has been reported to produce serious, often life-threatening, disease in immunosuppressed patients with a variety of diagnoses. The impact of this virus on the young child after heart transplantation has not been reported. METHODS: We reviewed the charts of 28 children who were <10 years of age at heart transplantation and had at least 1 year of follow-up. The median follow-up period was 7 years (1.4-13.0 years). All were seronegative for varicella-zoster virus before transplantation. Fourteen (50%) developed varicella at a median time posttransplantation of 3.3 years. The first 7 were admitted for intravenous acyclovir for 3 days followed by oral acyclovir for 7 days. The last 7 were treated as outpatients with oral valacyclovir for 7 days (n = 6) or with oral acyclovir for 10 days (n = 1). RESULTS: Intravenous and oral regimens both were well tolerated and were without complications. No patient was receiving steroids at the time that they developed their initial episode of varicella. One patient was receiving steroids for therapy of posttransplantation lymphoproliferative disease when she developed recurrent varicella or generalized zoster. No episodes of rejection were attributed to the varicella-zoster virus infection. There were no episodes of localized zoster. All patients experienced seroconversion from undetectable to detectable antibody titers early after varicella, and 12 of the 14 patients continued to have persistent detectable titers in late follow-up. Two of the 14 who received chemotherapy or enhanced immunosuppression after retransplantation transiently lost detectable varicella-zoster virus antibodies but currently have detectable titers. CONCLUSIONS: Primary varicella-zoster infection was well tolerated in our young pediatric heart transplant recipients, with no serious complications. We now reserve inpatient/intravenous therapy for those who are unable to tolerate oral medications or those who are receiving enhanced immunosuppression.

Acyclovir↗
PubMed2003

The role of antivirals in the management of neuropathic pain in the older patient with herpes zoster.

Herpes zoster has been known since ancient times. It is a ubiquitous disease, occurring sporadically without any seasonal preference and is caused by the varicella-zoster virus. It may be defined as an endogenous relapse of the primary infection varicella. Herpes zoster is characterised by typical efflorescences in the innervation region of a cranial or spinal nerve and starts and ends with pain of varying intensity. Currently, several antiviral drugs are approved and many studies have shown that antiviral therapy, started early in the course of disease, can significantly reduce the risk and the duration of postherpetic neuralgia in elderly patients. The effects of all antivirals discussed in this article, given either orally or intravenously, are comparable with regards to the resolution of virus replication, prevention of dissemination of skin lesions and reduction of acute herpes zoster pain. Valaciclovir (valacyclovir), famciclovir and brivudine (brivudin) are comparably effective in the reduction of the incidence and/or prevention of zoster-associated pain and postherpetic neuralgia. Brivudine 125mg once daily is as effective as famciclovir 250mg three times daily in reducing the prevalence and the duration of zoster-associated pain and postherpetic neuralgia, especially if therapy is combined with a structured-pain therapy. The intensity of the therapy for pain should depend on the intensity of the pain that it is treating. Famciclovir and brivudine offer an advantage over other antivirals because they are administered less frequently; this is particularly relevant for elderly patients who may already be taking a number of medications for other diseases. Therefore, antiviral therapy in combination with adequate pain management should be given to all elderly patients as soon as herpes zoster is diagnosed.

2-Aminopurine↗
PubMed2002

Prognostic factors of postherpetic neuralgia.

The investigation was aimed to determine prognostic factors related to postherpetic neuralgia (PHN), and treatment options for preventing PHN. The data showed 34 (17.0%) out of 188 patients with herpes zoster had severe pain after 4 weeks, and 22 (11.7%) after 8 weeks, compared with 109 (58.0%) at presentation. The age (>/=50 yr), surface area involved (>/=9%), and duration of severe pain (>/=4 weeks) might be the main factors that lead to PHN. On the other hand, gender, dermatomal distribution, accompanied systemic conditions, and interval between initial pain and initiation of treatment might not be implicated in PHN. The subjects were orally received antiviral (valacyclovir), tricyclic antidepressant (amitriptyline), and analgesic (ibuprofen) as the standard treatment in the group 1. In addition to the standard medication, lidocaine solution was sub- and/or perilesionally injected in the group 2, while lidocaine plus prilocaine cream was topically applied to the skin lesions in the group 3. The rates of PHN in the 3 treatment groups were not significantly different, suggesting adjuvant anesthetics may not be helpful to reduce the severity of pain.

Acyclovir↗
PubMed2006

Prophylactic perioperative antiviral therapy for LASIK in patients with inactive herpetic keratitis.

PURPOSE: To report the outcome of LASIK in patients with inactive herpetic keratitis in which perioperative antiviral prophylaxis was used to prevent the recurrence of ocular herpes. METHODS: We report an uncontrolled series of five patients with inactive herpetic keratitis for at least 1 year before surgery in whom LASIK was successfully performed. All patients showed normal topography, pachymetry, and corneal sensitivity with no central corneal scarring. Perioperative prophylaxis was used in each case with oral valacyclovir and topical acyclovir ointment. RESULTS: None of the eyes developed reactivation of herpetic keratitis during follow-up. CONCLUSIONS: This study suggests that perioperative antiviral prophylaxis may protect the cornea from herpes simplex virus reactivation after LASIK.

Acyclovir↗
PubMed1999

Antiviral agents for non-human immunodeficiency virus infections.

Several new agents for treating viral infections have been developed in recent years. All available agents are virustatic, inhibiting specific steps in the process of viral replication. No agent is active against nonreplicating or latent viruses. Acyclovir is useful in the treatment of genital herpes, herpes simplex encephalitis, mucocutaneous herpetic infection, varicella infection in the immunosuppressed host, and herpes zoster infection in the normal and the immunosuppressed host. It can also be used for prevention of herpesvirus infection in immunocompromised patients. Ganciclovir is indicated for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome and is effective in the treatment and prevention of cytomegalovirus infection in other immunocompromised patients. Famciclovir and valacyclovir are effective in the management of herpes simplex and varicella-zoster infection. Amantadine and rimantadine are useful therapeutically and prophylactically in the management of influenza A virus infection. Chronic hepatitis B infection can respond to lamivudine therapy, and the optimal treatment of hepatitis C is the combination of interferon alfa and ribavirin. Despite pronounced toxic effects, foscarnet and cidofovir are effective antiviral agents in specific settings.

2-Aminopurine↗
PubMed2000

Infectious complications of pentostatin therapy.

Managing the infectious complications associated with pentostatin (Nipent), used alone or in combination with other agents in patients with low-grade lymphomas, poses a significant problem for clinicians. Since there is limited experience with these therapies, definitive treatment recommendations concerning prophylaxis cannot be made. The panel members discussed the use of valacyclovir (Valtrex) to provide prophylaxis for herpes zoster, trimethoprim/sulfamethoxazole for Pneumocystis, and acyclovir (Zovirax) for varicella zoster. They also considered combinations of pentostatin with agents such as interferon, rituximab (Rituxan), and chlorambucil (Leukeran) and their effect on the immune system. The biology of B and T cells was discussed, with an emphasis on clinical application.

Acyclovir↗
PubMed2000

Recent advances in management of genital herpes.

OBJECTIVE: To provide an update on new diagnostic tests and antiviral strategies for managing genital herpes. QUALITY OF EVIDENCE: Treatment guidelines are based on randomized clinical trials and recommendations from the Expert Working Group on Canadian Guidelines for Sexually Transmitted Diseases. Recommendations concerning other aspects of managing genital herpes (e.g., indications for using type-specific serologic tests) are mainly based on expert opinion. MAIN MESSAGE: Genital herpes is one of the most common sexually transmitted diseases, affecting about 20% of sexually active people; up to 80% of cases are undiagnosed. Because of frequent atypical presentation and the emotional burden associated with genital herpes, clinical diagnosis should be confirmed by viral culture. Type-specific serologic assays are now available, but their use is often restricted to special situations and requires adequate counseling. New antivirals (valacyclovir and famciclovir) with improved pharmacokinetic profiles have now been approved for episodic treatment of recurrences and suppressive therapy. CONCLUSION: Wise use of new diagnostic assays for herpes simplex coupled with more convenient treatment regimens should provide better management of patients with genital herpes.

2-Aminopurine↗
PubMedDate not supplied

[Effect of the Epstein-Barr virus on the nervous system].

On the basis of a comprehensive examination of 12 patients with verified Epstein-Barr virus (EBV) infection it has been shown that this infection can be accompanied by acute and chronic affections of the central and peripheral nervous system. The pathogenesis of chronic EBV-infection involves autoimmune disorders, neurosensitization, a hazard of an injury to the muscular tissue. Chronic EBV-infection calls for differential diagnosis with other slow virus infections, systemic tumor afflictions, systemic diseases of the connective tissue. Acyclovir or valacyclovir can be recommended as treatment of acute and chronic EBV-infection.

Acyclovir↗
PubMed2002

Acute herpetic gingivostomatitis in adults: a review of 13 cases, including diagnosis and management.

OBJECTIVE: To present to general dentists the typical signs and symptoms associated with adult acute (primary) herpetic gingivostomatitis. The pertinent laboratory tests, management options and current pharmacotherapy are also reviewed. REVIEW DESIGN: The clinical files of 13 adult patients were reviewed. All had no history of herpes simplex virus infection and presented with oral lesions suggestive of primary herpetic infection. The subjects were all patients of one of the investigators, and their workup included Tzanck testing and viral culture. RESULTS: The patients ranged in age from 18 to 79 (mean 37.2, standard deviation 19.6) years. Nine (69%) were men. Viral culture was confirmed as the gold standard for diagnosis. The sensitivity of Tzanck testing was 77% (10/13), slightly higher than that reported previously (40% to 50%). In this patient group the febrile lymphadenopathic profile was typical of younger patients (18 to 42 years of age), whereas older patients presented with predominantly oral symptoms. CONCLUSIONS: Primary herpetic gingivostomatitis is not limited to children but can affect people of any age. Proper diagnosis and treatment are essential, particularly in elderly and immunocompromised patients. Tzanck testing may serve as a useful adjunct in diagnosis. Antiviral agents such as valacyclovir and famciclovir should be considered part of early management. Dentists are often the first health care professionals to be consulted by patients with this condition, and recognition of the infection is paramount.

2-Aminopurine↗
PubMed2003

Recurrent herpes simplex labialis: selected therapeutic options.

Recurrent infection with herpes simplex virus 1 (HSV1), called herpes simplex labialis (HSL), is a global problem for patients with normal immune systems. An effective management program is needed for those with frequent HSL recurrences, particularly if associated morbidity and life-threatening factors are present and the patient's immune status is altered. Over the past 20 years, a variety of antiviral compounds (acyclovir, penciclovir, famciclovir, valacyclovir) have been introduced that may reduce healing time, lesion size and associated pain. Classical lesions are preceded by a prodrome, but others appear without warning, which makes them more difficult to treat. Various methods of application (intravenous, oral, topical) are used, depending on whether the patient is experiencing recurrent HSL infection or erythema multiforme or is scheduled to undergo a dental procedure, a surgical procedure or a dermatological face peel (the latter being known triggers for recurrence). This article outlines preferred treatment (including drugs and their modes of application) for adults and children in each situation, which should assist practitioners wishing to use antiviral therapy.

2-Aminopurine↗
PubMed2004

Treatment of postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a serious complication of herpes zoster that has a predilection for older individuals. PHN is often associated with significant morbidity, and it can cause insomnia, fatigue, depression and interference with daily activities in affected individuals. Treatment for PHN is initiated with antivirals during the acute herpes zoster outbreak. Acyclovir (Zoviraxr, GlaxoSmithKline), valacyclovir (Valtrex, GlaxoSmithKline) or famciclovir (Famvir, Novartis) can be used to treat herpes zoster, and all three have been shown to reduce the duration of the herpetic rash and zoster-associated pain. These antivirals are most effective when used within the first 72 hours of the onset of the rash. Side-effects of these antivirals are low and include nausea, vomiting, abdominal pain and headache. Other treatment options for PHN include topical analgesics, opioid analgesics, tricyclic antidepressants and gabapentin. Because of the complexity of PHN, most patients require a combination of treatment modalities for adequate pain relief.

2-Aminopurine↗
PubMed2005

[Arguments favouring the pharmacotherapy of Bells' palsy].

Some clinicians claim a spontaneous complete recovery of facial nerve function after Bell's palsy in more than 80% of patients. However, for elderly patients and patients with a severe paresis/paralysis this is not the case. The main cause of Bell's palsy is probably reactivation of latent herpes viruses. Recent literature supports treatment with corticosteroids and antiviral medication, inhibiting viral replication and reducing oedema in the bony canal of the facial nerve. Using this medication in the first days of the disease provides a further 15% of patients with a good outcome in addition to the ones that improve spontaneously. Therefore, prednisone and valacyclovir are recommended for all patients with Bell's palsy and severe dysfunction, i.e. House-Brackmann facial grading scale IV, V and VI.

Acyclovir↗
PubMedDate not supplied

Antiviral therapy for genital herpes in nonpregnant and pregnant women.

There have been major developments in basic and clinical research in the field of antiviral therapy. The health care provider needs to know the availability of numerous antiviral compounds and begin to view them as we do antibiotics. They need to be used selectively to modify infections and prevent the morbidity and mortality associated with viral infections, such as herpes simplex virus (HSV, genital herpes). Therapy of these infections is required to treat not only the patient but also to prevent infection of sexual partners and the newborn. Numerous and varied antiviral compounds have been approved by the FDA to treat genital HSV infections. They all have the same mechanism of action. Acyclovir, valacyclovir, and famciclovir have been approved for the treatment of primary and recurrent disease. All three agents can be used for daily administration for the suppression of recurrent disease. Use of these antiviral compounds in the nonpregnant and pregnant woman can significantly alter the disease and influence transmission rates along with decreasing the morbidity and mortality associated with HSV infections.

2-Aminopurine↗
PubMed2003

Phase II study of alemtuzumab in chronic lymphoproliferative disorders.

BACKGROUND: Pilot studies showed that alemtuzumab is active in lymphoproliferative disorders. The authors conducted a Phase II trial to evaluate the efficacy and safety of alemtuzumab in advanced or refractory chronic lymphoproliferative disorders. METHODS: Seventy-eight patients were enrolled. The most common diagnoses were chronic lymphocytic leukemia (n = 42 patients) and T-cell prolymphocytic leukemia (n = 18 patients). Before entering the study, the patients had received multiple therapies (median, three therapies) and the median time from diagnosis was 7 years. Alemtuzumab was given intravenously at doses of 3 mg, 10 mg, and 30 mg on 3 consecutive days, after which 30 mg was administered 3 times a week. Patients were treated for 4-12 weeks depending on disease response. All patients received prophylactic trimethoprim/sulfamethoxazole and valacyclovir. RESULTS: The overall response rate was 35%, the complete response (CR) rate was 13%, and the partial response (PR) rate was 22%. The median duration of response was 18 months for patients achieving a CR and 7 months for patients achieving a PR. The median duration of survival was 25 months for patients who had a response and 12 months for the entire population. Normalization of the lymphocyte count was observed in 84% of patients and resolution of bone marrow involvement was observed in 49% of patients. The most common infusion-related adverse events were fever, rigors, skin rash, nausea, and dyspnea. These were most common during the first week of therapy. Hematologic toxicity was comprised of long-lasting lymphocytopenia and transient neutropenia and thrombocytopenia. Thirty-six patients (46%) experienced at least one episode of fever or infection. CONCLUSIONS: Alemtuzumab has a high response rate in patients with chronic lymphoproliferative disorders.

Adult↗
PubMed2006

Routine clinical use of alemtuzumab in patients with heavily pretreated B-cell chronic lymphocytic leukemia: a nation-wide retrospective study in Austria.

BACKGROUND: In previous studies, alemtuzumab demonstrated considerable activity in patients with previously treated B-cell chronic lymphocytic leukemia (CLL), including fludarabine-refractory disease. In this retrospective study, the authors evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced, previously treated CLL who received treatment in the routine clinical setting. METHODS: Data were collected from 115 consecutive patients who received alemtuzumab therapy at 25 participating centers in Austria. Patients received a median of 3 prior lines of therapy (range, 1-11 prior lines of therapy), and 59% had fludarabine-refractory disease. Alemtuzumab was administered intravenously or subcutaneously with a planned schedule of 30 mg 3 times per week for up to 12 weeks. Patients received valacyclovir and trimethoprim/sulfamethoxazole for antiinfective prophylaxis. RESULTS: The overall response rate was 23%, with complete responses achieved in 5% of patients. Stable disease (SD) was achieved in 36% of patients. After a median follow-up of 17.5 months, the median overall survival (OS) was 20.2 months for all patients. A multivariate Cox regression analysis that included pretreatment baseline characteristics, response to therapy, and cumulative dose of alemtuzumab indicated that bulky lymphadenopathy, the administration of > r =3 previous therapies, and lack of response to alemtuzumab remained significant independent risk factors for inferior OS. The median OS had not been reached for responding patients. The median OS was 29.5 months for patients with SD and 10.8 months for patients with progressive disease. CONCLUSIONS: The broad use of alemtuzumab in the routine clinical practice setting is feasible and active in unselected patients with pretreated CLL, and the current results confirmed the activity and safety of this agent, as reported in previously published clinical studies.

Aged↗
PubMed2000

Structural requirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2.

Peptide transporters PEPT1 and PEPT2 transport numerous compounds including small peptides, peptide-like drugs and nonpeptidic compounds such as valacyclovir. PEPT1 and PEPT2 show low and high affinity for most substrates, respectively, but beta-lactam antibiotics without an alpha-amino group are the only known substrates that prefer PEPT1 to PEPT2. The aim of this study was to compare the recognition and affinity of various substrates between rat PEPT1 and rat PEPT2, and to determine the structural requirements influencing the substrate affinity. [14C]Glycylsarcosine uptake by PEPT1- or PEPT2-expressing transfectant was inhibited by di- and tripeptides, but not by amino acids, tetrapeptides or most cyclic dipeptides. All dipeptides and tripeptides examined showed more potent inhibition of [14C]glycylsarcosine uptake via PEPT2 than via PEPT1, irrespective of their charge and structure. Modification of the alpha-amino group of dipeptides reduced their substrate affinity to both transporters, as compared to unmodified dipeptides, but these dipeptides still showed potent inhibitory effects on PEPT2. Among the nonpeptidic substrates tested, only the eight-amino-octanoic acid displayed stronger inhibition of [14C]glycylsarcosine uptake in PEPT1 than in PEPT2. These findings suggest that alpha- or beta-amino carbonyl function is the key structure responsible for the higher affinity for PEPT2 than for PEPT1.

Animals↗
PubMed1998

Esophageal Infections.

Infectious esophagitis is a common problem in immunocompromised patients that can result in prolonged discomfort and malnutrition. Common infectious causes of esophagitis can be confirmed by laboratory testing, but esophagoscopy is often necessary not only to visualize the esophageal mucosa but also to obtain diagnostic biopsies. Empiric, systemic antifungal or antiherpetic therapies are often prescribed prior to confirming an etiologic diagnosis in esophagitis. In some cases, however, endoscopy is needed to guide therapy. Systemic antifungal therapy is usually superior to topical therapy for Candida esophagitis, and the first choice of agent is generally fluconazole. Valacyclovir or famciclovir are the preferred first treatments for herpetic esophagitis because of their clinical efficacy and convenient dosing schedules. Thalidomide may be useful in the management of aphthous ulcerations of the mouth and esophagus in patients with HIV.

Journal Article↗