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Christophe Legendre - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of lowering immunosuppression to treat cmv infection in renal transplant recipients on Valaciclovir prophylaxis a pilot study
Nephrology Dialysis Transplantation, 2003Co-Authors: Dany Anglicheau, Alexandre Lautrette, Catherine Scieux, Martin Flamant, Frederic Morinet, Christophe LegendreAbstract:Background. Routine cytomegalovirus (CMV)-pp65 antigenaemia monitoring shows that some patients will develop pp65 antigenaemia during Valaciclovir prophylaxis or after cessation of treatment. The aim of this pilot study was to evaluate the safety and efficacy of lowering immunosuppression in kidney transplant recipients who exhibit mildly symptomatic CMV infections while on Valaciclovir prophylaxis. Methods. We selected 12 patients who experienced mildly symptomatic CMV infections defined as a positive CMV-pp65 antigenaemia test associated with either neutropenia, asthenia or arthralgia, but no fever. All of them received prophylaxis with Valaciclovir for at least 3 months. Testing for CMV-pp65 antigenaemia was performed weekly for 6 months. Results. The mildly symptomatic infections occurred at a median interval of 69 days after transplantation-during prophylaxis in eight cases and after Valaciclovir discontinuation in the other four cases. All of them were effectively managed by lowering immunosuppressive therapy, leading to the disappearance of symptoms and CMV antigenaemia reduction. No immunological complication or recurrence of CMV infection or disease was noted. I.v. ganciclovir never became necessary. Conclusion. The mildly symptomatic CMV infections occurring in Valaciclovir-treated patients may be managed efficiently and without immunologic complication by lowering immunosuppressive therapy.
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Valaciclovir prophylaxis of cytomegalovirus infection and disease in renal transplantation: an economic evaluation.
Transplantation, 2000Co-Authors: Christophe Legendre, Douglas J. Norman, Michael R. Keating, G. D. H. Maclaine, D. M. GrantAbstract:BACKGROUND Cytomegalovirus (CMV) disease is a major cause of morbidity and mortality in solid organ transplant patients and is associated with large additional healthcare expenditures. An economic evaluation of Valaciclovir CMV prophylaxis in a renal transplant population is reported. METHODS Medical resource use data were collected alongside a multicenter multinational randomized, placebo-controlled, double-blind trial of Valaciclovir CMV prophylaxis in renal transplantation. Patients were stratified into donor seropositive/recipient sero-negative (D+R-) and recipient seropositive (R+) groups. Patients were followed-up 6 months posttransplant. A cost-effectiveness analysis from the perspective of the French health care system was performed using the number of cases of CMV disease avoided at 6 months as the clinical endpoint. RESULTS Resource use was significantly increased among patients who developed CMV disease compared to those who did not develop disease. In the high risk D+R- group, Valaciclovir prophylaxis was associated with an average of 5.5 fewer inpatient hospital days (P < OR =0.05) and with significantly lower use of other healthcare resources. In the R+ group, Valaciclovir prophylaxis prevented cases of CMV disease at a marginally greater mean cost per patient compared with placebo. For D+R- patients Valaciclovir prophylaxis was therefore an economically superior strategy, resulting in fewer cases of CMV disease and lower total mean healthcare expenditures. CONCLUSIONS Valaciclovir CMV prophylaxis in renal transplantation is a more cost-effective therapy compared with placebo, in the high-risk D+R- patient population. For the R+ group, the incremental cost per case of CMV disease was modest.
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valacyclovir for the prevention of cytomegalovirus disease after renal transplantation
The New England Journal of Medicine, 1999Co-Authors: David Lowance, Christophe Legendre, Douglas J. Norman, Michael R. Keating, Hans H Neumayer, Jeanpaul Squifflet, Josef Kovarik, Patrick J Brennan, Rafael Mendez, Gary L CoggonAbstract:Background Cytomegalovirus (CMV) disease is a major complication of organ transplantation. We hypothesized that prophylactic treatment with valacyclovir would reduce the risk of CMV disease. Methods A total of 208 CMV-negative recipients of a kidney from a seropositive donor and 408 CMV-positive recipients were randomly assigned to receive either 2 g of valacyclovir or placebo orally four times daily for 90 days after transplantation, with the dose adjusted according to renal function. The primary end point was laboratory-confirmed CMV disease in the first six months after transplantation. Results Treatment with valacyclovir reduced the incidence or delayed the onset of CMV disease in both the seronegative patients (P<0.001) and the seropositive patients (P=0.03). Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo recipients and 3 percent among valacyclovir recipients. Among the seropositive patients, the respective values were 6 percent and 0 percent. At six months, the incidence of CMV disease was 45 percent among seronegative recipients of placebo and 16 percent among seronegative recipients of valacyclovir; it was 6 percent among seropositive placebo recipients and 1 percent among seropositive valacyclovir recipients. At six months, the rate of biopsy-confirmed acute graft rejection in the seronegative group was 52 percent among placebo recipients and 26 percent among valacyclovir recipients (P=0.001). Treatment with valacyclovir also decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources. Hallucinations and confusion were more common with valacyclovir treatment, but these events were not severe or treatment limiting. The rates of other adverse events were similar among the groups. Conclusions Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation. (N Engl J Med 1999; 340:1462-70.) (C) 1999, Massachusetts Medical Society.
Karl R. Beutner - One of the best experts on this subject based on the ideXlab platform.
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a large scale placebo controlled dose ranging trial of peroral Valaciclovir for episodic treatment of recurrent herpes genitalis
JAMA Internal Medicine, 1996Co-Authors: Spotswood L. Spruance, Stephen K. Tyring, B Degregorio, C Miller, Karl R. BeutnerAbstract:Background: Valaciclovir, the 1-valyl ester of acyclovir, has provided a peroral acyclovir bioavailability 3 to 5 times that of acyclovir itself and is rapidly and completely converted to acyclovir by the liver. Accordingly, Valaciclovir has the same antiviral activity as acyclovir, but the potential for enhanced clinical activity and/or less frequent administration because of its superior pharmacokinetics. Methods: We conducted a double-blind, placebo-controlled, patient-initiated clinical trial of peroral Valaciclovir, 500 or 1000 mg, or matching placebo tablets twice daily for 5 days for the acute treatment of 1 episode of recurrent herpes genitalis among 987 otherwise healthy volunteers. Results: Both doses of Valaciclovir were equally effective. Patients receiving the lower dose of Valaciclovir experienced a median episode length of 4.0 days compared with 5.9 days for those receiving placebo treatment (hazard ratio, 1.9; 95% confidence interval [CI], 1.6-2.3). Valaciclovir therapy increased the proportion of patients in whom the development of vesicular and ulcer-ative lesions was prevented in comparison with placebo treatment: 31% vs 21% (relative risk, 1.5; 95% CI, 1.1-1.9). Valaciclovir therapy accelerated the resolution of pain (hazard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral shedding (hazard ratio, 2.9; 95% CI, 2.1-3.9). Adverse reactions among the Valaciclovir groups were comparable with those of the placebo group. Conclusions: Valaciclovir therapy provided a clinically significant benefit to patients that included shortening of the duration of lesions, the duration of pain or discomfort, and the duration of virus shedding. In addition, this study, to our knowledge, provides the first convincing demonstration that antiviral therapy can prevent lesion development. These results should prompt a reconsideration of the role that episodic treatment plays in the management of recurrent herpes genitalis. Arch Intern Med. 1996;156:1729-1735
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A large-scale, placebo-controlled, dose-ranging trial of peroral Valaciclovir for episodic treatment of recurrent herpes genitalis. Valaciclovir HSV Study Group.
Archives of Internal Medicine, 1996Co-Authors: Spotswood L. Spruance, Stephen K. Tyring, B Degregorio, C Miller, Karl R. BeutnerAbstract:Background Valaciclovir, the 1-valyl ester of acyclovir, has provided a peroral acyclovir bioavailability 3 to 5 times that of acyclovir itself and is rapidly and completely converted to acyclovir by the liver. Accordingly, Valaciclovir has the same antiviral activity as acyclovir, but the potential for enhanced clinical activity and/or less frequent administration because of its superior pharmacokinetics. Methods We conducted a double-blind, placebocontrolled, patient-initiated clinical trial of peroral Valaciclovir, 500 or 1000 mg, or matching placebo tablets twice daily for 5 days for the acute treatment of 1 episode of recurrent herpes genitalis among 987 otherwise healthy volunteers. Results Both doses of Valaciclovir were equally effective. Patients receiving the lower dose of Valaciclovir experienced a median episode length of 4.0 days compared with 5.9 days for those receiving placebo treatment (hazard ratio, 1.9; 95% confidence interval [Cl], 1.6-2.3). Valaciclovir therapy increased the proportion of patients in whom the development of vesicular and ulcerative lesions was prevented in comparison with placebo treatment: 31% vs 21% (relative risk, 1.5; 95% CI, 1.1-1.9). Valaciclovir therapy accelerated the resolution of pain (hazard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral shedding (hazard ratio, 2.9; 95% CI, 2.1-3.9). Adverse reactions among the Valaciclovir groups were comparable with those of the placebo group. Conclusions Valaciclovir therapy provided a clinically significant benefit to patients that included shortening of the duration of lesions, the duration of pain or discomfort, and the duration of virus shedding. In addition, this study, to our knowledge, provides the first convincing demonstration that antiviral therapy can prevent lesion development. These results should prompt a reconsideration of the role that episodic treatment plays in the management of recurrent herpes genitalis.
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valacyclovir a review of its antiviral activity pharmacokinetic properties and clinical efficacy
Antiviral Research, 1995Co-Authors: Karl R. BeutnerAbstract:: Oral administration of the prodrug valacyclovir results in enhanced bioavailability and significantly greater plasma concentrations of acyclovir than can be achieved with oral doses of acyclovir itself. The results of clinical trials with valacyclovir have demonstrated significant benefits in the resolution of pain associated with herpes zoster infection. Efficacy parameters were similar for valacyclovir and acyclovir in the treatment of herpes simplex; however the results were achieved with lower and less-frequent doses of valacyclovir. The cost of a course of therapy with valacyclovir is expected to be similar to that of other antivirals. The potential clinical benefits of valacyclovir will likely be apparent in the case of acyclovir-resistant herpesvirus infections, where high-dose intravenous treatment with acyclovir has been necessary. Most of these resistant viruses have been encountered in immunocompromised patients, and the resistance has been attributed to inadequate exposure to the drug. Because optimal levels of acyclovir are achieved with a simpler dosing regimen of valacyclovir, compliance may be improved in many patients, thus reducing the incidence of resistant virus.
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Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults
Antimicrobial Agents and Chemotherapy, 1995Co-Authors: Karl R. Beutner, C Forszpaniak, P L Andersen, D.j. Friedman, M J WoodAbstract:Acyclovir treatment of acute herpes zoster speeds rash healing and decreases pain and ocular complications. The limited oral bioavailability of acyclovir necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, is rapidly and almost completely converted to acyclovir in vivo and gives three- to fivefold increases in acyclovir bioavailability. In a randomized, double-blind, multicenter study, the safety and efficacy of oral Valaciclovir given at a dosage of 1,000 mg three times daily for 7 or 14 days and oral acyclovir given at a dosage of 800 mg five times daily for 7 days were compared in immunocompetent adults aged > or = 50 years with herpes zoster. Patients were evaluated for 6 months. The intent-to-treat analysis (1,141 patients) showed that Valaciclovir for 7 or 14 days significantly accelerated the resolution of herpes zoster-associated pain (P = 0.001 and P = 0.03, respectively) compared with acyclovir; median pain durations were 38 and 44 days, respectively, versus 51 days for acyclovir. Treatment with Valaciclovir also significantly reduced the duration of postherpetic neuralgia and decreased the proportion of patients with pain persisting for 6 months (19.3 versus 25.7%). However, there were no differences between treatments in pain intensity or quality-of-life measures. Cutaneous manifestations resolved at similar rates in all groups. Adverse events were similar in nature and prevalence among groups, and no clinically important changes occurred in hematology or clinical chemistry parameters. Thus, in the management of immunocompetent patients > or = 50 years of age with localized herpes zoster, Valaciclovir given at 1,000 mg three times daily for 7 days accelerates the resolution of pain and offers simpler dosing, while it maintains the favorable safety profile of acyclovir.
Lawrence Corey - One of the best experts on this subject based on the ideXlab platform.
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safety and pharmacokinetics of aciclovir in women following release from a silicone elastomer vaginal ring
Journal of Antimicrobial Chemotherapy, 2012Co-Authors: Marla J Keller, Lawrence Corey, Amanda M Malone, Colleen Carpenter, Yungtai Lo, Meei Li Huang, R Willis, Cali Nguyen, Sean Kennedy, Manjula GunawardanaAbstract:OBJECTIVES: Systemic aciclovir and its prodrug Valaciclovir are effective in treating and reducing recurrences of genital herpes simplex virus (HSV) and reducing transmission. Local aciclovir delivery, if it can achieve and maintain comparable intracellular genital tract levels, may be equally effective in the treatment and suppression of genital HSV. Intravaginal ring (IVR) delivery of aciclovir may provide pre-exposure prophylaxis against HSV acquisition. METHODS: Tolerability and pharmacokinetics were evaluated in six HIV-negative women with recurrent genital HSV who switched their daily oral Valaciclovir suppression to an aciclovir IVR for 7 days (n = 3) or 14 days (n = 3). Blood and cervicovaginal lavage (CVL) were collected after oral and IVR dosing to measure aciclovir concentrations and genital swabs were obtained to quantify HSV shedding by PCR. RESULTS: The rings were well tolerated. Median plasma aciclovir concentrations were 110.2 ng/mL (IQR, 85.9-233.5) 12-18 h after oral Valaciclovir. Little or no drug was detected in plasma following IVR dosing. Median (IQR) CVL aciclovir levels were 127.3 ng/mL (21-660.8) 2 h after oral Valaciclovir, 154.4 ng/mL (60.7-327.5) 12-18 h after oral Valaciclovir and 438 ng/mL (178.5-618.5) after 7 days and 393 ng/mL (31.6-1615) after 14 days of aciclovir ring use. Median CVL aciclovir levels 2 h after oral dosing were similar to levels observed 7 (P = 0.99) and 14 (P = 0.75) days after ring use. HSV DNA was not detected in genital swabs and there was no significant change in inflammatory mediators. CONCLUSIONS: This first-in-human study demonstrated that an IVR could safely deliver mucosal levels of aciclovir similar to oral Valaciclovir without systemic absorption. More intensive site-specific pharmacokinetic studies are needed to determine whether higher local concentrations are needed to achieve optimal drug distribution within the genital tract.
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valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract
The Journal of Infectious Diseases, 2004Co-Authors: Rachna Gupta, Mauricio Vargascortes, Gerri B Miller, Terri Warren, Stacy Selke, Lawrence Corey, Elizabeth M Krantz, Anna WaldAbstract:6 GlaxoSmithKline, Research Triangle Park, North Carolina Background. Valacyclovir exhibits better oral absorption and higher, more prolonged serum concentrations than oral acyclovir. The efficacy of valacyclovir and acyclovir on genital herpes simplex virus (HSV) shedding was assessed in a double-blind, 3-period crossover trial. Methods. Sixty-nine immunocompetent participants with genital HSV-2 received oral valacyclovir, acyclovir, and matching placebo in random order for 7-week periods. Participants provided daily genital mucosal swabs for HSV detection by viral culture and polymerase chain reaction (PCR). Results. HSV was detected at least once in 62 (90%) participants by culture and in 68 (98%) by PCR. During placebo, the total HSV shedding rate was 15.4% of days by culture (PCR, 40.2%); the subclinical shedding rate was 6.6% by culture (PCR, 27.1%). Both antivirals were associated with lower HSV shedding by culture (relative risk (RR), 0.03 (95% confidence interval {CI}, 0.01-0.07) for valacyclovir and RR, 0.05 (95% CI, 0.03-0.10) for acyclovir) and PCR (RR, 0.18 (95% CI, 0.12-0.26) for valacyclovir and RR, 0.20 (95% CI, 0.15-0.28) for acyclovir), compared with placebo. No significant differences in frequency and quantity of HSV were detected by PCR between the valacyclovir and acyclovir arms. Conclusions. Although the suppression of viral replication is not complete, valacyclovir and acyclovir are highly effective in suppressing the frequency and quantity of genital HSV shedding.
Stephen K. Tyring - One of the best experts on this subject based on the ideXlab platform.
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Valacyclovir in the Treatment of Herpes Simplex, Herpes Zoster, and Other Viral Infections
Journal of Cutaneous Medicine and Surgery: Incorporating Medical and Surgical Dermatology, 2003Co-Authors: Jashin J. Wu, Mathijs H. Brentjens, Gisela Torres, Kimberly Yeung–yue, Stephen K. TyringAbstract:Background: Genital herpes and herpes labialis are prevalent, physically and pychologically painful, and often disabling. Herpes zoster is often very painful and may result in months or years of postherpetic neuralgia (PHN). Over the past two decades, the treatment of these conditions has been transformed by guanosine nucleoside antivirals such as valacyclovir (Valtrex^®), a highly bioavailable prodrug of acyclovir (Zovirax^®), and famciclovir (Famvir^®), a highly bioavailable prodrug of penciclovir (Denavir^®). Objective: We describe the pharmacology, pharmacokinetics, and clinical efficacy of valacyclovir for the treatment of herpes simplex, herpes zoster, and other viral infections. Valacyclovir is also compared with acyclovir and famciclovir. Methods: All published literature containing the word “valacyclovir” was reviewed and summarized. Results: Valacyclovir is the only oral antiviral agent approved for therapy of herpes labialis, the only antiviral drug approved for a 3-day course in the episodic treatment of recurrent genital herpes, as well as the only antiviral drug approved for once daily dosing for suppressive therapy. In herpes zoster, valacyclovir is more effective than acyclovir and equally effective as famciclovir at hastening the healing of zoster-associated pain and PHN. Conclusion: Valacyclovir is safe and effective in the therapy of patients with herpes simplex and herpes zoster and may be useful in other viral infections. L’herpès génital et l’herpès labial sont des affections courantes, physiquement et psychologiquement douloureuses et souvent invalidantes. Le zona est souvent très douloureux et peut causer des mois, voir des années, de névralgie postherpétique. Au cours des deux dernières décennies, le traitement de ces affections a été transformé grâce aux antiviraux nucléosides guansonines, tels que le Valaciclovir (Valtrex), un prodrogue hautement biodisponible de l’aciclovir (Zovirax), et le famciclovir (Famvir), un prodrogue hautement biodisponible du penciclovir (Denavir). Objectifs: Description de la pharmacologie, de la pharmacocinétique et de l’efficacité clinique du Valaciclovir dans le traitement de l’herpès simplex, du zona et d’autres infections virales. Également, le Valaciclovir est comparé à l’aciclovir et au famciclovir. Méthodes: Revue et résumé de toutes les publications contenant le terme «Valaciclovir». Résultats: Le Valaciclovir est le seul agent antiviral oral approuvé dans le traitement de l’herpès labial. Il est aussi le seul médicament antiviral approuvé pour un traitement sur trois jours dans le cas de l’herpès génital récidivant et pour une dose quotidienne dans le cas d’un traitement suppressif. Dans les cas de zona, le Valaciclovir est plus efficace que l’aciclovir et aussi efficace que le famciclovir dans le traitement rapide de la douleur et de la névralgie postherpétique. Conclusion: L’efficacité et l’innocuité du Valaciclovir ont été établies dans le traitement des patients atteints d’herpès simplex et de zona. Il peut également servir au traitement d’autres infections virales.
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Valaciclovir for the suppression of recurrent genital herpes simplex virus infection a large scale dose range finding study
The Journal of Infectious Diseases, 1998Co-Authors: M Reitano, Stephen K. Tyring, W Lang, C Thoming, A M Worm, S Borelli, L O Chambers, J M Robinson, L CoreyAbstract:A randomized, double-blind study of Valaciclovir for suppression of recurrent genital herpes was conducted among 1479 immunocompetent patients. Patients were randomized to receive Valaciclovir (250 mg, 500 mg, or 1 g once daily, or 250 mg twice daily), acyclovir (400 mg twice daily), or placebo, for 1 year. All Valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences (P <.0001). There was a dose-response relationship (P <.0001) across the once-daily Valaciclovir regimens. Twice-daily Valaciclovir and acyclovir were similar in effectiveness. Subgroup analysis showed that patients with a history of < 10 recurrences per year were effectively managed with 500 mg of Valaciclovir once daily. One gram of Valaciclovir once daily, 250 mg of Valaciclovir twice daily, or 400 mg of acyclovir twice daily were more effective in patients with ≥ 10 recurrences per year. Safety profiles of all treatments were comparable. Thus, Valaciclovir is highly effective and well tolerated for suppression of recurrent genital herpes. Once-daily regimens offer a useful option for patients who require suppressive therapy for management of genital herpes.
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Valaciclovir for the Suppression of Recurrent Genital Herpes Simplex Virus Infection: A Large-Scale Dose Range-Finding Study
The Journal of Infectious Diseases, 1998Co-Authors: M Reitano, Stephen K. Tyring, W Lang, C Thoming, A M Worm, S Borelli, L O Chambers, J M Robinson, L CoreyAbstract:A randomized, double-blind study of Valaciclovir for suppression of recurrent genital herpes was conducted among 1479 immunocompetent patients. Patients were randomized to receive Valaciclovir (250 mg, 500 mg, or 1 g once daily, or 250 mg twice daily), acyclovir (400 mg twice daily), or placebo, for 1 year. All Valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences (P
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A large-scale, placebo-controlled, dose-ranging trial of peroral Valaciclovir for episodic treatment of recurrent herpes genitalis. Valaciclovir HSV Study Group.
Archives of Internal Medicine, 1996Co-Authors: Spotswood L. Spruance, Stephen K. Tyring, B Degregorio, C Miller, Karl R. BeutnerAbstract:Background Valaciclovir, the 1-valyl ester of acyclovir, has provided a peroral acyclovir bioavailability 3 to 5 times that of acyclovir itself and is rapidly and completely converted to acyclovir by the liver. Accordingly, Valaciclovir has the same antiviral activity as acyclovir, but the potential for enhanced clinical activity and/or less frequent administration because of its superior pharmacokinetics. Methods We conducted a double-blind, placebocontrolled, patient-initiated clinical trial of peroral Valaciclovir, 500 or 1000 mg, or matching placebo tablets twice daily for 5 days for the acute treatment of 1 episode of recurrent herpes genitalis among 987 otherwise healthy volunteers. Results Both doses of Valaciclovir were equally effective. Patients receiving the lower dose of Valaciclovir experienced a median episode length of 4.0 days compared with 5.9 days for those receiving placebo treatment (hazard ratio, 1.9; 95% confidence interval [Cl], 1.6-2.3). Valaciclovir therapy increased the proportion of patients in whom the development of vesicular and ulcerative lesions was prevented in comparison with placebo treatment: 31% vs 21% (relative risk, 1.5; 95% CI, 1.1-1.9). Valaciclovir therapy accelerated the resolution of pain (hazard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral shedding (hazard ratio, 2.9; 95% CI, 2.1-3.9). Adverse reactions among the Valaciclovir groups were comparable with those of the placebo group. Conclusions Valaciclovir therapy provided a clinically significant benefit to patients that included shortening of the duration of lesions, the duration of pain or discomfort, and the duration of virus shedding. In addition, this study, to our knowledge, provides the first convincing demonstration that antiviral therapy can prevent lesion development. These results should prompt a reconsideration of the role that episodic treatment plays in the management of recurrent herpes genitalis.
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a large scale placebo controlled dose ranging trial of peroral Valaciclovir for episodic treatment of recurrent herpes genitalis
JAMA Internal Medicine, 1996Co-Authors: Spotswood L. Spruance, Stephen K. Tyring, B Degregorio, C Miller, Karl R. BeutnerAbstract:Background: Valaciclovir, the 1-valyl ester of acyclovir, has provided a peroral acyclovir bioavailability 3 to 5 times that of acyclovir itself and is rapidly and completely converted to acyclovir by the liver. Accordingly, Valaciclovir has the same antiviral activity as acyclovir, but the potential for enhanced clinical activity and/or less frequent administration because of its superior pharmacokinetics. Methods: We conducted a double-blind, placebo-controlled, patient-initiated clinical trial of peroral Valaciclovir, 500 or 1000 mg, or matching placebo tablets twice daily for 5 days for the acute treatment of 1 episode of recurrent herpes genitalis among 987 otherwise healthy volunteers. Results: Both doses of Valaciclovir were equally effective. Patients receiving the lower dose of Valaciclovir experienced a median episode length of 4.0 days compared with 5.9 days for those receiving placebo treatment (hazard ratio, 1.9; 95% confidence interval [CI], 1.6-2.3). Valaciclovir therapy increased the proportion of patients in whom the development of vesicular and ulcer-ative lesions was prevented in comparison with placebo treatment: 31% vs 21% (relative risk, 1.5; 95% CI, 1.1-1.9). Valaciclovir therapy accelerated the resolution of pain (hazard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral shedding (hazard ratio, 2.9; 95% CI, 2.1-3.9). Adverse reactions among the Valaciclovir groups were comparable with those of the placebo group. Conclusions: Valaciclovir therapy provided a clinically significant benefit to patients that included shortening of the duration of lesions, the duration of pain or discomfort, and the duration of virus shedding. In addition, this study, to our knowledge, provides the first convincing demonstration that antiviral therapy can prevent lesion development. These results should prompt a reconsideration of the role that episodic treatment plays in the management of recurrent herpes genitalis. Arch Intern Med. 1996;156:1729-1735
L Corey - One of the best experts on this subject based on the ideXlab platform.
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Valaciclovir for the suppression of recurrent genital herpes simplex virus infection a large scale dose range finding study
The Journal of Infectious Diseases, 1998Co-Authors: M Reitano, Stephen K. Tyring, W Lang, C Thoming, A M Worm, S Borelli, L O Chambers, J M Robinson, L CoreyAbstract:A randomized, double-blind study of Valaciclovir for suppression of recurrent genital herpes was conducted among 1479 immunocompetent patients. Patients were randomized to receive Valaciclovir (250 mg, 500 mg, or 1 g once daily, or 250 mg twice daily), acyclovir (400 mg twice daily), or placebo, for 1 year. All Valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences (P <.0001). There was a dose-response relationship (P <.0001) across the once-daily Valaciclovir regimens. Twice-daily Valaciclovir and acyclovir were similar in effectiveness. Subgroup analysis showed that patients with a history of < 10 recurrences per year were effectively managed with 500 mg of Valaciclovir once daily. One gram of Valaciclovir once daily, 250 mg of Valaciclovir twice daily, or 400 mg of acyclovir twice daily were more effective in patients with ≥ 10 recurrences per year. Safety profiles of all treatments were comparable. Thus, Valaciclovir is highly effective and well tolerated for suppression of recurrent genital herpes. Once-daily regimens offer a useful option for patients who require suppressive therapy for management of genital herpes.
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Valaciclovir for the Suppression of Recurrent Genital Herpes Simplex Virus Infection: A Large-Scale Dose Range-Finding Study
The Journal of Infectious Diseases, 1998Co-Authors: M Reitano, Stephen K. Tyring, W Lang, C Thoming, A M Worm, S Borelli, L O Chambers, J M Robinson, L CoreyAbstract:A randomized, double-blind study of Valaciclovir for suppression of recurrent genital herpes was conducted among 1479 immunocompetent patients. Patients were randomized to receive Valaciclovir (250 mg, 500 mg, or 1 g once daily, or 250 mg twice daily), acyclovir (400 mg twice daily), or placebo, for 1 year. All Valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences (P
