Valtrex or valacyclovir
Failure of valacyclovir for herpes zoster in a moderately immunocompromised HIV-infected patient.

Vilde JL.

Department of Infectious and Tropical Diseases Bichat Claude Bernard Hospital, Paris, France. guillaume.breton bch.ap-hop-paris.fr

Whereas valacyclovir is widely used and is recommended by some authors in moderately immunocompromised HIV-infected patients, its use has not been validated by clinical studies. We report a case of herpes zoster in an HIV-infected patient for whom neurologic complication was not avoided despite valacyclovir therapy. Clinical outcome was favorable after intravenous acyclovir. This case suggests careful monitoring of valacyclovir in HIV-infected patients is necessary.

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Valtrex or valacyclovir
The effect of valacyclovir treatment on natural killer cells of infertile women.

Tsilivakos V.

Department of infertility, Locus Medicus Laboratory, Athens, Greece.

PROBLEM: The aim of this study was to investigate the effect of valacyclovir treatment on natural killer (NK) cell concentration in the peripheral blood of infertile women. METHOD OF STUDY: Peripheral blood NK cell concentration of 104 non-pregnant women with a history of infertility was determined by flow cytometry. The controls were 14 fertile non-pregnant women. A cohort of 42 out of 104 women--whose NK cell levels were 175/microL or higher--was prospectively studied for the presence of HSV-1, 2, VZV, cytomegalovirus, HHV-6, HHV-7 and HHV-8 DNA in the peripheral blood and was orally administered valacyclovir (open label study). RESULTS: Herpes virus DNA was detected in 64.3% of the 42 women examined. Prior to valacyclovir treatment mean NK cell concentration in herpes-negative group was statistically higher from control group but lower from herpes positive group (P = 0.0007, ANOVA). Following valacyclovir treatment the mean NK cell concentration was statistically decreased in all studied women (P = 0.000453), in herpes-negative (P = 0.01622) and in herpes positive group (P = 0.0056). Sufficient decrease was observed in 31 (73.8%) of 42 women who received the drug. CONCLUSIONS: Valacyclovir treatment is associated with a decrease of NK cell levels in most of the women with a history of infertility.

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Valtrex or valacyclovir
Persistence and transition of Epstein-Barr virus genotypes in the pathogenesis of oral hairy leukoplakia.

Nichols CM.

Division of Infectious Diseases, Department of Internal Medicine, and Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA. dwalling utmb.edu

This prospective study examined the persistence and transition of Epstein-Barr virus (EBV) in human immunodeficiency virus (HIV)-seropositive subjects with and without oral hairy leukoplakia, a replicative EBV-associated epithelial disease. The intrahost molecular epidemiology of EBV infection was characterized in subjects treated with valacyclovir to suppress EBV replication. Tongue epithelial tissues of HIV-seropositive subjects were found to support not only EBV replication but also persistent, nonproductive EBV infection. EBV appeared to enter the tongue from the blood reservoir of infection and, possibly, from exogenous sources as well. EBV transition from the blood to the tongue appeared to occur even during valacyclovir-mediated suppression of EBV replication, suggesting EBV entry into tongue epithelial tissue as a cell-associated latent infection. In conclusion, these results describe the persistence and transition of EBV as a dynamic interaction between the blood and epithelial reservoirs of EBV infection and suggest a role for entry, persistence, and reactivation of oral epithelial EBV in the pathogenesis of oral hairy leukoplakia.

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Valtrex or valacyclovir
Detection of ganciclovir resistance after valacyclovir-prophylaxis in renal transplant recipients with active cytomegalovirus infection.

Denis F.

Department of Bacteriology-Virology-Hygien, EA, Teaching Hospital Dupuytren, Limoges, France. sophie.alain unilim.fr

Whether valaciclovir (VCV) prophylaxis could be responsible for ganciclovir (GCV)-resistance of Human cytomegalovirus (HCMV) in transplantation has never been documented. A multicentric retrospective pilot study was undertaken to detect GCV-resistance through mutations within the UL97 gene in renal transplant recipients who experienced active HCMV infection and received valacyclovir prophylaxis. Twenty-three patients who experienced HCMV antigenaemia or DNAemia during or at the end of prophylaxis were included. UL97 genotyping was carried out on peripheral blood samples, using a nested in-house PCR, which amplified the full-length UL97 gene. One patient has a resistance-related mutation (M460I); the major risk factor for emergence of resistance in this patient was the presence of early and persistent antigenaemia. GCV-resistance during VCV-prophylaxis was rare after renal transplantation. However, special attention must be paid to patients developing early active HCMV infection under prophylaxis. Copyright 2004 Wiley-Liss, Inc.

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Valtrex or valacyclovir
Prevention of perinatal herpes: prophylactic antiviral therapy?

Scott LL.

University of Miami School of Medicine, Department of Obstetrics and Gynecology, Plantation, FL 33324, USA. LLScottMD aol.com

So what is the take-home message from these studies? The first question, about fetal and neonatal safety, appears to be answered positively. With more than 1,812 infants reported to have been exposed to varying amounts and duration of maternal acyclovir suppression, there has not been any apparent, short-term adverse fetal or neonatal effect. Use of acyclovir in infants, even in those that are premature, is very well tolerated, with a wide margin of safety. In addition, the pharmacokinetics studies by Frenkel et al and Kimberlin et al, as well as the animal studies, suggest that maternal use of acyclovir may actually provide a prophylactic and therapeutic benefit to an infant who is exposed to HSV. The second question, as to whether acyclovir suppression would simply change symptomatic outbreaks into asymptomatic ones, also appears to have some answers. The information provided by Wald et al indicated that acyclovir suppression actually decreases asymptomatic shedding, along with decreasing clinical recurrences. Because asymptomatic shedding seems to be similar in pregnant and nonpregnant patients, it would be reasonable to assume that asymptomatic shedding also would be decreased at delivery in pregnant women with HSV infection. This supposition is supported by the data from the randomized trials and cohort studies that demonstrated a lower than expected asymptomatic shedding rate. As yet, however, there has been no randomized trial in pregnant women that has had an adequate sample size to confirm this on a statistically significant basis. The third question, whether acyclovir suppression would lower the frequency of symptomatic recurrences at parturition, reducing the need for cesarean in these patients, has answers as well, although they may not be as clear cut as one would like. Women who experience their first genital herpes outbreak while they are pregnant seem to benefit from acyclovir suppression, with both a decrease in the risk of clinical recurrences at delivery and a decreased need for cesarean delivery. This is well documented by a randomized trial and other cohort studies. Acyclovir's efficacy in patients who have a history of genital herpes infections antedating their pregnancy is less clear. The data appear to indicate a clinically important decrease in the likelihood of symptomatic reactivations at the time of delivery, although the sample sizes in the randomized studies have been too small to draw a statistically significant conclusion one way or the other. Unfortunately, a definitive trial for this group of women may never be done. Assuming a 13% recurrence risk at the time of delivery and a 50% decrease in recurrences with the use of acyclovir, 652 women would have to complete the study to achieve a power of 80%. Conducting the study at the largest, single institution, prenatal center in the United States, Scott et al were only able to enroll 222 women during a period of 6 years. Likewise, Brocklehurst et al terminated their trial early because of recruitment difficulties. They enrolled only 63 women during a period of 4 years using two different sites in the United Kingdom. Unless a multicenter trial is conducted or a meta-analysis performed on the available data, we will probably have to be content with the data as it now stands. With valacyclovir and famciclovir now available, it is unlikely that any further work will be done with acyclovir. Information from the valacyclovir trials, however, may reach statistical significance because of changes in the study design that will allow smaller sample sizes to reach adequate power. Famciclovir treatment holds promise because of its longer intracellular half-life, but until concerns about potential mutagenicity are resolved and more information on its efficacy for suppressive therapy becomes available, it should not be considered for maternal suppressive therapy. Acyclovir appears to be effective, at least in some cohorts, and is probably safe for the fetus. (AB

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