valacyclovir and Chronic-Disease

Treatment of genital herpes requires accurate diagnosis, patient support, and effective treatment. Diagnosis is usually straightforward for classic presentations characterized by vesicular lesions but can be challenging for atypical presentations, which are more common. Diagnosis of asymptomatic infection requires access to molecular technology or type-specific serologic assays. Misconceptions about herpes simplex infection are common and patient education is essential. Patient concerns extend beyond disease frequency and severity-the psychological impact should not be underestimated. Antiviral therapy is relevant at all stages of infection. Acyclovir, valacyclovir, and famciclovir are effective and well tolerated for genital herpes treatment. Continuous suppressive therapy controls all symptoms of recurrent disease and helps to relieve disease complications. The prodrugs valacyclovir and famciclovir offer easier, less-frequent dosing than required for acyclovir. Valacyclovir achieves effective suppression when taken once a day. Interventions to prevent genital herpes transmission and to control the global problem are urgently required.

Topics: 2-Aminopurine; Acute Disease; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antibodies, Viral; Antiviral Agents; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Famciclovir; Herpes Genitalis; Herpesvirus 1, Human; Herpesvirus 2, Human; HIV Infections; Humans; Immunocompetence; Patient Education as Topic; Prodrugs; Secondary Prevention; Treatment Outcome; Valacyclovir; Valine

After herpes zoster, immunocompetent persons frequently experience chronic pain and considerable suffering. Zoster-associated pain has a complex pathophysiology that begins with viral damage and increased sensitization of peripheral sensory neurons. The enhanced afferent barrage from these neurons sensitizes spinal neurons and leads to loss of synapses from descending inhibitory fibers, resulting in central neuropathic pain and allodynia. Antiviral therapy of acute zoster limits this sequence of pathophysiologic mechanisms. There is no clear consensus regarding the optimal means of determining the benefits of antiviral therapy in the management of pain of herpes zoster. A novel statistical approach utilizing rates of disappearance of pain of differing pathophysiologic mechanisms is proposed.

Topics: 2-Aminopurine; Acyclovir; Analgesics; Antiviral Agents; Chronic Disease; Clinical Trials as Topic; Famciclovir; Herpes Zoster; Herpesvirus 3, Human; Humans; Meta-Analysis as Topic; Pain; Pain Measurement; Proportional Hazards Models; Treatment Outcome; Valacyclovir; Valine

Herpes simplex virus infection is increasingly common in the United States. New antiviral medications have expanded treatment options for the two most common cutaneous manifestations, orolabial and genital herpes. Acyclovir therapy remains an effective and often less expensive option. Famciclovir and valacyclovir offer improved oral bioavailability and convenient oral dosing schedules but are more expensive than acyclovir. Patients who have six or more recurrences of genital herpes per year can be treated with one of the following regimens: acyclovir, 400 mg twice daily; valacyclovir, 1 g daily; or famciclovir, 250 mg twice daily. These regimens are effective in suppressing 70 to 80 percent of symptomatic recurrences. Episodic treatment of recurrent genital herpes is of questionable benefit, but it may be helpful in appropriately selected patients. There is little evidence indicating benefit from treatment of recurrent orolabial herpes, which tends to be mild and infrequent.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Chronic Disease; Diagnosis, Differential; Drug Costs; Famciclovir; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans; Patient Education as Topic; Teaching Materials; Valacyclovir; Valine

With the US population aging steadily, herpes zoster represents a growing contributor to diminished quality of life. Dermatologic manifestations appear as immunity declines with age but rarely pose a significant threat, except in instances when ocular structures are involved. Pain is of more concern, because it usually accompanies and may even precede and persist after acute eruptions. In most young patients, pain is transient and bearable. Unfortunately, in the elderly--who are at highest risk for herpes zoster--pain is often more prolonged and more intense. In spite of a wide spectrum of interventions, palliative efforts remain rather ineffectual. At present, intervening as early as possible, ideally within 48 to 72 hours of disease onset, offers the greatest chance of minimizing neurologic sequelae. Inoculation with varicella vaccine in patients between ages 55 and 65 may prove to boost cell-mediated immunity sufficiently so that recrudescence of the varicella virus can be relegated to the annals of history.

Topics: 2-Aminopurine; Acute Disease; Acyclovir; Aged; Antiviral Agents; Chronic Disease; Famciclovir; Herpes Zoster; Humans; Neuralgia; Risk Factors; Valacyclovir; Valine

Marginal rate-based analyses are widely used for the analysis of recurrent events in clinical trials. In many areas of application, the events are not instantaneous but rather signal the onset of a symptomatic episode representing a recurrent infection, respiratory exacerbation, or bout of acute depression. In rate-based analyses, it is unclear how to best handle the time during which individuals are experiencing symptoms and hence are not at risk. We derive the limiting value of the Nelson-Aalen estimator and estimators of the regression coefficients under a semiparametric rate-based model in terms of an underlying two-state process. We investigate the impact of the distribution of the episode durations, heterogeneity, and dependence on the asymptotic and finite sample properties of standard estimators. We also consider the impact of these features on power in trials designed to test intervention effects on rate functions. An application to a trial of individuals with herpes simplex virus is given for illustration.

Topics: Antiviral Agents; Chronic Disease; Computer Simulation; Cross-Over Studies; Female; Herpes Simplex; Humans; Male; Models, Statistical; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Recurrence; Valacyclovir

Topics: Acyclovir; Anti-HIV Agents; Antiviral Agents; Chronic Disease; HIV Infections; HIV-1; Humans; Male; Penile Diseases; Skin Ulcer; Valacyclovir; Valine; Young Adult

Chronic cutaneous varicella zoster virus (VZV) infection has not been previously reported or characterized as a complication of dermatomyositis. Two patients with non-malignancy-associated dermatomyositis, treated with long-term prednisone and methotrexate, developed persistent, painless ulcers ultimately established to be secondary to chronic VZV. The absence of pain or a history suggestive of acute VZV, and the lack of characteristic histopathology, resulted in a lengthy delay in diagnosis. Polymerase chain reaction and tissue immunohistochemistry were positive for VZV, and treatment with valacyclovir resulted in complete clearance. Diagnostic testing for VZV should thus be considered in the evaluation of ulcerative lesions in patients with dermatomyositis. The increased incidence of acute VZV in combination with the nature and duration of immunosuppressive treatment in this patient population may be contributory.

Topics: Acyclovir; Aged; Antiviral Agents; Chronic Disease; Dermatomyositis; Female; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Immunosuppressive Agents; Skin Diseases, Viral; Valacyclovir; Valine

Hydroa vacciniforme is one of the rarest forms of photosensitivity disorders of the skin. Effective treatment options are scarce and mainly constitute of strict sun protection. Lately, hydroa vacciniforme has been associated with Epstein-Barr virus infection. We present a patient with hydroa vacciniforme and concomitant previous/chronic Epstein-Barr virus infection. In this case, antiviral treatment was successful.

Topics: Acyclovir; Antiviral Agents; Child; Chronic Disease; Epstein-Barr Virus Infections; Humans; Hydroa Vacciniforme; Male; Valacyclovir; Valine

Valacyclovir, the L-valyl ester prodrug of acyclovir (ACV), is widely prescribed to treat infections caused by varicella-zoster virus or herpes simplex virus. Rarely, treatment is complicated by reversible neuropsychiatric symptoms. By mechanisms not fully understood, this occurs more frequently in the setting of renal impairment. We characterized the steady-state pharmacokinetics of ACV and its metabolites 9-[(carboxymethoxy)methyl]guanine (CMMG) and 8-hydroxy-acyclovir (8-OH-ACV) in cerebrospinal fluid (CSF) and the systemic circulation. We administered multiple doses of high-dose valacyclovir to 6 subjects with normal renal function and 3 subjects with chronic renal impairment (creatinine clearance [CrCl], approximately 15 to 30 ml/min). Dosages were 2,000 mg every 6 h and 1,500 mg every 12 h, respectively. Indwelling intrathecal catheters allowed serial CSF sampling throughout the dosing interval. The average steady-state concentrations of acyclovir, CMMG, and 8-OH-ACV were greater in both the systemic circulation and the CSF among subjects with impaired renal function than among subjects with normal renal function. However, the CSF penetration of each analyte, reflected by the CSF-to-plasma area under the concentration-time curve over the 6- or 12-h dosing interval (AUC(tau)) ratio, did not differ based on renal function. Renal impairment does not alter the propensity for ACV or its metabolites to distribute to the CSF, but the higher concentrations in the systemic circulation, as a result of reduced elimination, are associated with proportionally higher concentrations in CSF.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Chronic Disease; Female; Guanine; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Male; Medical Futility; Middle Aged; Prodrugs; Valacyclovir; Valine; Young Adult

Epstein-Barr virus (EBV) infection occurring in the postoperative period represents a significant risk for pediatric transplant recipients. It presents in various manners, including a mononucleosis-like syndrome, hepatitis, encephalopathy, or posttransplant lymphoproliferative disease (PTLD). Valacyclovir has in vitro activity against EBV. We sought to review our experience with valacyclovir on peripheral blood EBV viral loads among a group of EBV-infected patients after liver transplantation (OLT).. Twelve children of ages 6-36 months (median, 12 months), underwent OLT. Eight (66%) were EBV immunoglobulin (Ig)G seronegative at the time of the operation. Eight patients developed primary infection and 4 patients developed reactivation of a post primary infection. Valacyclovir was prescribed immediately to 3 patients when we detected an acute-primary EBV infection. Valacyclovir was prescribed for 2 patients who had primary EBV infections followed by PTLD. Three patients who had primary EBV infection were administered valacyclovir after they became chronically EBV PCR positive for more than 1 year. Four out of 12 cases (33%) were EBV seropositive at the time of OLT, and underwent postprimary EBV reactivation displaying chronic EBV carrier state for 8-10 months before valacyclovir treatment. Peripheral blood EBV viral loads were tested every 2 months. The primary outcome was the proportion of subjects with EBV viremia who had a >or=2 log 10 decrease in EBV copies/mL after valacyclovir treatment. The duration of valacyclovir treatment was a median of 10 months (range, 8-11 months). At the beginning of the treatment period the median level of EBV viral load was 1.1 x 10(4) (range, 1 x 10(4) to 1 x 10(7)). EBV virus was cleared in only 1 patient with primary acute EBV infection. EBV viral loads did not change in 7 of 12 patients and decreased only 1 log 10 (n = 2) or 2 log 10 (n = 2).. In this small, non-placebo-controlled study, valacyclovir treatment was not effective to decrease peripheral blood EBV viral loads.

Topics: Acute Disease; Acyclovir; Antiviral Agents; Body Weight; Child, Preschool; Chronic Disease; Epstein-Barr Virus Infections; Humans; Infant; Liver Function Tests; Liver Transplantation; Postoperative Complications; Recurrence; Retrospective Studies; Valacyclovir; Valine; Viral Load; Virus Activation

To report the case of an immunocompetent child with herpes simplex virus-2 (HSV-2) acute retinal necrosis (ARN) syndrome, who was considered to have an idiopathic unilateral panuveitis sensitive to steroid treatment.. Polymerase chain reaction for detection of viral DNA was applied to ocular fluids and in situ hybridization was performed on a retinal sample. HSV serology was performed using the ELISA and Western blot techniques, and an in-house indirect immunofluorescence technique.. In addition to the atypical clinical presentation, the serological assays for HSV were negative using ELISA at the time of diagnosis of ARN and 1 year after. HSV2 infection was confirmed by using polymerase chain reaction of aqueous humor specimen and in situ hybridization of a retinal biopsy. Retrospective analysis with the Western blot technique detected low titers of anti-HSV antibodies, when the sera were concentrated 5-fold.. Herpes virus infections must be investigated in children with posterior or panuveitis. PCR analysis is a reliable technique for diagnosis. This case emphasizes that clinical presentation can be atypical and that a negative viral serology does not exclude an acute or a past herpetic infection.

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Aqueous Humor; Child, Preschool; Chronic Disease; DNA, Viral; Enzyme-Linked Immunosorbent Assay; Eye Infections, Viral; Herpes Simplex; Herpesvirus 2, Human; Humans; In Situ Hybridization; Male; Panuveitis; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Valacyclovir; Valine

We report on a chronic asymptomatic hepatitis B surface antigen (HBsAg) carrier who developed an increase in aminotransferase and HBsAg levels 1 year after lung transplantation. During treatment for cutaneous herpes simplex virus (HSV) infection with oral valaciclovir there was a marked decrease in replicating hepatitis B virus (HBV)-DNA and aminotransferase levels, which was sustained for 9 months by continuing low-dose valaciclovir. A second rise in aminotransferase levels again responded to a valaciclovir dose increase and the HBV-DNA levels declined further. Although we cannot exclude a spontaneous variation of the serologic parameters, our observation suggests that valaciclovir may represent a valuable therapeutic option in the treatment of chronic hepatitis B after lung transplantation.

Topics: Acyclovir; Bronchiectasis; Carrier State; Chronic Disease; Female; Follow-Up Studies; Graft Survival; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Lung Transplantation; Middle Aged; Postoperative Complications; Preoperative Care; Risk Assessment; Serologic Tests; Treatment Outcome; Valacyclovir; Valine

A 34-year-old healthy woman presented with a 15-month history of persistent, nonhealing vulvar ulcerations due to herpes simplex virus (HSV) type 2. Extensive dermatologic workup and serial skin biopsies failed to reveal an underlying vulvar dermatosis or autoimmune bullous disorder. Virologic studies revealed resistance to acyclovir in vitro due to deficiency in thymidine kinase activity. Serum antibody to human immunodeficiency virus was negative on two occasions, separated by 1 year. Immunologic evaluation showed normal HSV-specific proliferative and CD8 cytotoxic T lymphocyte responses as well as normal NK cell function. Vulvar lesions failed to heal in association with trials of topical trifluorothymidine and oral valacyclovir but resolved completely with the application of 1% foscarnet cream. No recurrence of HSV has been observed in 24 months of follow-up to date.

Topics: Acyclovir; Antiviral Agents; Chronic Disease; Drug Resistance, Microbial; Female; Foscarnet; Humans; Immunocompetence; Simplexvirus; Thymidine Kinase; Ulcer; Valacyclovir; Valine; Vulvar Diseases