The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform
Lawrence Corey - One of the best experts on this subject based on the ideXlab platform.
-
valAcyclovir and Acyclovir for suppression of shedding of herpes simplex virus in the genital tract
The Journal of Infectious Diseases, 2004Co-Authors: Rachna Gupta, Lawrence Corey, Anna Wald, Elizabeth M Krantz, Stacy Selke, Terri Warren, Mauricio Vargascortes, Gerri B MillerAbstract: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.
-
a double blind randomized placebo controlled trial of Acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery
American Journal of Obstetrics and Gynecology, 2003Co-Authors: Heather D Watts, Stacy Selke, Zane A Brown, Deborah Money, Meei Li Huang, Stephen L Sacks, Lawrence CoreyAbstract:Abstract Objective: The purpose of this study was to assess the efficacy of Acyclovir in the reduction of herpes simplex virus culture and polymerase chain reaction positivity and cesarean delivery. Study Design: Women with recurrent genital herpes simplex virus were randomized to Acyclovir 400 mg three times daily or placebo from 36 weeks of gestation until delivery. A subset of daily specimens for herpes simplex virus culture and DNA polymerase chain reaction was self-collected. Analyses used χ 2 , Fisher exact, and Mann-Whitney U tests. Results: Lesions occurred at delivery among 11 of 78 women (14%) who received placebo and 4 of 84 women (5%) who received Acyclovir ( P =.08). Herpes simplex virus culture and polymerase chain reaction positivity near delivery occurred in 7% and 34% women in the placebo group and 0 and 2% in the Acyclovir group ( P =.03 and P =.17). Despite reductions in herpes simplex virus detection, 6% of the women who received Acyclovir had herpes simplex virus detected by polymerase chain reaction on >20% of days. Neonatal outcomes were similar between groups. Conclusion: Acyclovir significantly reduced, but did not eliminate, herpes simplex virus lesions and detection in late pregnancy. (Am J Obstet Gynecol 2003;188:836-43.)
-
safety and efficacy of high dose intravenous Acyclovir in the management of neonatal herpes simplex virus infections
Pediatrics, 2001Co-Authors: David W Kimberlin, Lawrence Corey, Richard F Jacobs, Dwight A Powell, William C Gruber, Mobeen H Rathore, John S Bradley, Pamela S Diaz, Mary L Kumar, Ann M ArvinAbstract:Objective. The objective of this investigation was to establish the safety of high-dose (HD) Acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD Acyclovir was also assessed. Participants. Infants who were ≤28 days old and whose disease was considered to be caused by HSV were enrolled in this study. Patients with central nervous system (CNS; N = 28) or disseminated (N = 41) HSV infection were offered participation in the trial. A small number of patients with HSV disease limited to the skin, eyes, or mouth (SEM; N = 10) or whose disease was clinically consistent with HSV but who did not have virologic confirmation of infection (N = 9) also were enrolled on a compassionate basis. Only patients with virologically confirmed HSV disease were included in efficacy analyses. All enrolled patients were included in safety analyses. Methods. The study was an open-label evaluation of intravenous Acyclovir at dosages higher than the 30 mg/kg/d standard dosage approved by the US Food and Drug Administration. The first 16 patients enrolled received intermediate-dose (ID) Acyclovir (45 mg/kg/d), and the next 72 patients received HD Acyclovir (60 mg/kg/d). Acyclovir was administered in 3 divided daily doses for 21 days. Neonates were assessed prospectively throughout treatment and at scheduled follow-up visits for the first 4 years of life. Data were compared with those of a previous National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial in which patients received standard-dose (SD) Acyclovir for 10 days and in which identical methods (with the exception of Acyclovir dosage and duration of therapy) were used. Results. Six (21%) of 29 HD Acyclovir recipients whose HSV disease remained localized to the SEM or CNS experienced neutropenia. One of the 6 had an absolute neutrophil count The survival rate for the patients with disseminated HSV disease treated with HD Acyclovir was significantly higher than for those in the previous study treated with SD Acyclovir, with an odds ratio (OR) of 3.3 (95% confidence interval [CI]: 1.4–7.9). For patients with CNS disease, however, survival rates were similar for the HD and SD groups. To assess the effect of HD Acyclovir on survival for the entire population with neonatal HSV disease, the Cox proportional hazards regression analysis was performed with stratification for disease category (CNS versus disseminated). In performing this analysis, differences in mortality for each disease category were weighted to allow statistical comparison of the treatment dosage groups (HD, ID, and SD). This analysis indicated that the survival rate for patients treated with HD Acyclovir was statistically significantly higher than for patients treated with SD Acyclovir (OR: 3.3; 95% CI: 1.5–7.3). Recipients of HD Acyclovir had a borderline significant decrease in morbidity compared with SD recipients, after stratification for the extent of disease (SEM vs CNS vs disseminated) and controlling for the potential confounding factors of HSV type (HSV-1 vs. HSV-2), prematurity, and disease severity (seizures). Patients treated with HD Acyclovir were 6.6 times (adjusted OR; 95% CI: 0.8–113.6) as likely to be developmentally normal at 12 months of age as patients treated with SD therapy. Conclusion. These data support the use of a 21-day course of HD (60 mg/kg/d) intravenous Acyclovir to treat neonatal CNS and disseminated HSV disease. Throughout the course of HD Acyclovir therapy, serial ANC determination should be made at least twice weekly. Decreasing the Acyclovir dosage or administering granulocyte colony-stimulating factor should be considered if the ANC remains below 500/mm3 for a prolonged period.
-
suppression of subclinical shedding of herpes simplex virus type 2 with Acyclovir
Annals of Internal Medicine, 1996Co-Authors: Anna Wald, Gail Barnum, L G Davis, Lawrence CoreyAbstract:Objective : To assess the effect of the antiviral drug Acyclovir on the frequency of subclinical shedding of herpes simplex virus (HSV) in the genital tract. Design : A double-blind, placebo-controlled, crossover clinical trial. Setting : A university-based virology research clinic. Patients : 34 women with herpes simplex virus type 2 (HSV-2) antibody only and genital herpes of less than 2 years' duration. Intervention : Participants were randomly assigned to receive either Acyclovir, 400 mg twice daily for 70 days, followed by a 14-day washout period, and then placebo for 70 days, or the study medications in the reverse order. Measurements : Women collected daily genital swabs of the vulvar, cervicovaginal, and perianal areas for HSV culture, maintained a diary of genital lesions, and were examined at the time of recurrences. Results : In an intent-to-treat analysis of the initial treatment period, 15 of the 17 women who received placebo and 3 of the 17 women who received Acyclovir had at least 1 day of subclinical shedding (P < 0.001). Among the participants who received placebo, subclinical shedding occurred on 64 of 928 (6.9%) days compared with 3 of 1057 (0.3%) days among the participants who received Acyclovir (P < 0.001). The relative risk for subclinical shedding was 0.09 (95% Cl, 0.03 to 0.35) for the women who received Acyclovir compared with the women who received placebo. In a paired analysis of 26 women who completed both arms of the study, Acyclovir therapy was associated with a decrease in the frequency of subclinical shedding ; subclinical shedding occurred on 83 of 1439 (5.8%) days with placebo, and on 6 of 1611 (0.37%) days with Acyclovir (P < 0.001)-a 94% reduction. The frequency of subclinical shedding was reduced at all anatomic sites and in all patients. Conclusions : Daily therapy with oral Acyclovir suppresses subclinical shedding of HSV-2 in the genital tract, suggesting that studies to evaluate the use of Acyclovir in preventing HSV-2 transmission are warranted.
Sharanappa T Nandibewoor - One of the best experts on this subject based on the ideXlab platform.
-
electrochemical behavior of an antiviral drug Acyclovir at fullerene c60 modified glassy carbon electrode
Bioelectrochemistry, 2012Co-Authors: Nagaraj P. Shetti, Shweta J. Malode, Sharanappa T NandibewoorAbstract:Abstract Electrochemical oxidation of Acyclovir at fullerene-C60-modified glassy carbon electrode has been investigated using cyclic and differential pulse voltammetry. In pH 7.4 phosphate buffer, Acyclovir showed an irreversible oxidation peak at about 0.96 V. The cyclic voltammetric results showed that fullerene-C60-modified glassy carbon electrode can remarkably enhance electrocatalytic activity towards the oxidation of Acyclovir. The electrocatalytic behavior was further exploited as a sensitive detection scheme for the Acyclovir determination by differential pulse voltammetry. Effects of anodic peak potential (Ep/V), anodic peak current (Ip/μA) and heterogeneous rate constant (k0) have been discussed. Under optimized conditions, the concentration range and detection limit were 9.0 × 10− 8 to 6.0 × 10− 6 M and 1.48 × 10− 8 M, respectively. The proposed method was applied to Acyclovir determination in pharmaceutical samples and human biological fluids such as urine and blood plasma as a real sample. This method can also be employed in quality control and routine determination of drugs in pharmaceutical formulations.
-
Electrochemical behavior of an antiviral drug Acyclovir at fullerene-C60-modified glassy carbon electrode
Bioelectrochemistry, 2012Co-Authors: Nagaraj P. Shetti, Shweta J. Malode, Sharanappa T NandibewoorAbstract:Electrochemical oxidation of Acyclovir at fullerene-C60-modified glassy carbon electrode has been investigated using cyclic and differential pulse voltammetry. In pH 7.4 phosphate buffer, Acyclovir showed an irreversible oxidation peak at about 0.96V. The cyclic voltammetric results showed that fullerene-C60-modified glassy carbon electrode can remarkably enhance electrocatalytic activity towards the oxidation of Acyclovir. The electrocatalytic behavior was further exploited as a sensitive detection scheme for the Acyclovir determination by differential pulse voltammetry. Effects of anodic peak potential (Ep/V), anodic peak current (Ip/μA) and heterogeneous rate constant (k0) have been discussed. Under optimized conditions, the concentration range and detection limit were 9.0×10-8to 6.0×10-6M and 1.48×10-8M, respectively. The proposed method was applied to Acyclovir determination in pharmaceutical samples and human biological fluids such as urine and blood plasma as a real sample. This method can also be employed in quality control and routine determination of drugs in pharmaceutical formulations. © 2012 Elsevier B.V.
Koji Izutsu - One of the best experts on this subject based on the ideXlab platform.
-
long term ultra low dose Acyclovir against varicella zoster virus reactivation after allogeneic hematopoietic stem cell transplantation
American Journal of Hematology, 2008Co-Authors: Yuki Asanomori, Yoshinobu Kanda, Kumi Oshima, Shinichi Kako, Akihito Shinohara, Hideki Nakasone, Hiroyuki Sato, Takuro Watanabe, Noriko Hosoya, Koji IzutsuAbstract:To evaluate the efficacy of long-term prophylaxis with ultra-low-dose Acyclovir against varicella-zoster virus (VZV) reactivation, we analyzed the records of 242 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2006 at our hospital. We started long-term oral Acyclovir at 200 mg/day in July 2001. Acyclovir was continued until the end of immunosuppressive therapy and at least 1 year after transplantation. Sixty-six patients developed VZV reactivation at a median of 248 days after HSCT, with a cumulative incidence of 34.7%. Only one breakthrough reactivation occurred during long-term Acyclovir, which responded well to therapeutic dose of valAcyclovir. The use of long-term Acyclovir was the only independent determinant that significantly decreased the overall incidence of VZV reactivation (20% vs. 50%, P < 0.0001). With this prophylaxis, visceral dissemination and serious complications other than post-herpetic neuralgia was completely eliminated, and thereby need for hospitalization was significantly reduced (21% vs. 71%, P = 0.0034). Fifteen of the 57 patients who discontinued Acyclovir developed VZV reactivation, with a cumulative incidence of 32.1%. VZV reactivation following discontinuation tended to occur in patients who were receiving immunosuppressive therapy at the cessation of Acyclovir. These findings suggested that long-term prophylaxis of ultra-low-dose Acyclovir resulted in a successful prevention of severe VZV-related symptoms and death, with a significantly decreased overall incidence of VZV reactivation. Prolongation of prophylactic Acyclovir on profound immunosuppression might be important for thorough suppression of VZV reactivation. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc.
-
long term ultra low dose Acyclovir against varicella zoster virus reactivation after allogeneic hematopoietic stem cell transplantation
Blood, 2007Co-Authors: Yuki Asanomori, Yoshinobu Kanda, Kumi Oshima, Shinichi Kako, Akihito Shinohara, Hideki Nakasone, Hiroyuki Sato, Takuro Watanabe, Noriko Hosoya, Koji IzutsuAbstract:Varicella-zoster virus (VZV) infection remains a common complication after hematopoietic stem cell transplantation (HSCT). The introduction of long-term prophylaxis with low-dose Acyclovir against VZV reactivation has been investigated, because VZV-related complications including post-herpetic neuralgia and secondary infection significantly affect the patient’s quality of life. We started long-term oral Acyclovir at 200 mg/day in July 2001. Acyclovir was continued until the end of immunosuppressive therapy and at least one year after transplantation. To evaluate the efficacy of this long-term prophylaxis with ultra low-dose Acyclovir against VZV reactivation, we analyzed the records of 242 Japanese adult patients who underwent allogeneic HSCT for the first time from June, 1995 to November, 2006 at University of Tokyo Hospital. Sixty-six patients developed VZV reactivation at a median of 248 days after HSCT, with a cumulative incidence of 34.7%. There was no VZV-related death. Only one breakthrough reactivation occurred during long-term Acyclovir, responding well to the therapeutic dose of valAcyclovir. The use of long-term Acyclovir was the only independent determinant that significantly decreased the overall incidence of VZV reactivation (20.4% vs 50.5%, P
Nagaraj P. Shetti - One of the best experts on this subject based on the ideXlab platform.
-
electrochemical behavior of an antiviral drug Acyclovir at fullerene c60 modified glassy carbon electrode
Bioelectrochemistry, 2012Co-Authors: Nagaraj P. Shetti, Shweta J. Malode, Sharanappa T NandibewoorAbstract:Abstract Electrochemical oxidation of Acyclovir at fullerene-C60-modified glassy carbon electrode has been investigated using cyclic and differential pulse voltammetry. In pH 7.4 phosphate buffer, Acyclovir showed an irreversible oxidation peak at about 0.96 V. The cyclic voltammetric results showed that fullerene-C60-modified glassy carbon electrode can remarkably enhance electrocatalytic activity towards the oxidation of Acyclovir. The electrocatalytic behavior was further exploited as a sensitive detection scheme for the Acyclovir determination by differential pulse voltammetry. Effects of anodic peak potential (Ep/V), anodic peak current (Ip/μA) and heterogeneous rate constant (k0) have been discussed. Under optimized conditions, the concentration range and detection limit were 9.0 × 10− 8 to 6.0 × 10− 6 M and 1.48 × 10− 8 M, respectively. The proposed method was applied to Acyclovir determination in pharmaceutical samples and human biological fluids such as urine and blood plasma as a real sample. This method can also be employed in quality control and routine determination of drugs in pharmaceutical formulations.
-
Electrochemical behavior of an antiviral drug Acyclovir at fullerene-C60-modified glassy carbon electrode
Bioelectrochemistry, 2012Co-Authors: Nagaraj P. Shetti, Shweta J. Malode, Sharanappa T NandibewoorAbstract:Electrochemical oxidation of Acyclovir at fullerene-C60-modified glassy carbon electrode has been investigated using cyclic and differential pulse voltammetry. In pH 7.4 phosphate buffer, Acyclovir showed an irreversible oxidation peak at about 0.96V. The cyclic voltammetric results showed that fullerene-C60-modified glassy carbon electrode can remarkably enhance electrocatalytic activity towards the oxidation of Acyclovir. The electrocatalytic behavior was further exploited as a sensitive detection scheme for the Acyclovir determination by differential pulse voltammetry. Effects of anodic peak potential (Ep/V), anodic peak current (Ip/μA) and heterogeneous rate constant (k0) have been discussed. Under optimized conditions, the concentration range and detection limit were 9.0×10-8to 6.0×10-6M and 1.48×10-8M, respectively. The proposed method was applied to Acyclovir determination in pharmaceutical samples and human biological fluids such as urine and blood plasma as a real sample. This method can also be employed in quality control and routine determination of drugs in pharmaceutical formulations. © 2012 Elsevier B.V.
Yoshinobu Kanda - One of the best experts on this subject based on the ideXlab platform.
-
long term ultra low dose Acyclovir against varicella zoster virus reactivation after allogeneic hematopoietic stem cell transplantation
American Journal of Hematology, 2008Co-Authors: Yuki Asanomori, Yoshinobu Kanda, Kumi Oshima, Shinichi Kako, Akihito Shinohara, Hideki Nakasone, Hiroyuki Sato, Takuro Watanabe, Noriko Hosoya, Koji IzutsuAbstract:To evaluate the efficacy of long-term prophylaxis with ultra-low-dose Acyclovir against varicella-zoster virus (VZV) reactivation, we analyzed the records of 242 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2006 at our hospital. We started long-term oral Acyclovir at 200 mg/day in July 2001. Acyclovir was continued until the end of immunosuppressive therapy and at least 1 year after transplantation. Sixty-six patients developed VZV reactivation at a median of 248 days after HSCT, with a cumulative incidence of 34.7%. Only one breakthrough reactivation occurred during long-term Acyclovir, which responded well to therapeutic dose of valAcyclovir. The use of long-term Acyclovir was the only independent determinant that significantly decreased the overall incidence of VZV reactivation (20% vs. 50%, P < 0.0001). With this prophylaxis, visceral dissemination and serious complications other than post-herpetic neuralgia was completely eliminated, and thereby need for hospitalization was significantly reduced (21% vs. 71%, P = 0.0034). Fifteen of the 57 patients who discontinued Acyclovir developed VZV reactivation, with a cumulative incidence of 32.1%. VZV reactivation following discontinuation tended to occur in patients who were receiving immunosuppressive therapy at the cessation of Acyclovir. These findings suggested that long-term prophylaxis of ultra-low-dose Acyclovir resulted in a successful prevention of severe VZV-related symptoms and death, with a significantly decreased overall incidence of VZV reactivation. Prolongation of prophylactic Acyclovir on profound immunosuppression might be important for thorough suppression of VZV reactivation. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc.
-
long term ultra low dose Acyclovir against varicella zoster virus reactivation after allogeneic hematopoietic stem cell transplantation
Blood, 2007Co-Authors: Yuki Asanomori, Yoshinobu Kanda, Kumi Oshima, Shinichi Kako, Akihito Shinohara, Hideki Nakasone, Hiroyuki Sato, Takuro Watanabe, Noriko Hosoya, Koji IzutsuAbstract:Varicella-zoster virus (VZV) infection remains a common complication after hematopoietic stem cell transplantation (HSCT). The introduction of long-term prophylaxis with low-dose Acyclovir against VZV reactivation has been investigated, because VZV-related complications including post-herpetic neuralgia and secondary infection significantly affect the patient’s quality of life. We started long-term oral Acyclovir at 200 mg/day in July 2001. Acyclovir was continued until the end of immunosuppressive therapy and at least one year after transplantation. To evaluate the efficacy of this long-term prophylaxis with ultra low-dose Acyclovir against VZV reactivation, we analyzed the records of 242 Japanese adult patients who underwent allogeneic HSCT for the first time from June, 1995 to November, 2006 at University of Tokyo Hospital. Sixty-six patients developed VZV reactivation at a median of 248 days after HSCT, with a cumulative incidence of 34.7%. There was no VZV-related death. Only one breakthrough reactivation occurred during long-term Acyclovir, responding well to the therapeutic dose of valAcyclovir. The use of long-term Acyclovir was the only independent determinant that significantly decreased the overall incidence of VZV reactivation (20.4% vs 50.5%, P
-
long term low dose Acyclovir against varicella zoster virus reactivation after allogeneic hematopoietic stem cell transplantation
Bone Marrow Transplantation, 2001Co-Authors: Yoshinobu Kanda, Shin Mineishi, Toshiki Saito, Akiko Saito, S Yamada, M Ohnishi, A Chizuka, H Niiya, K Suenaga, K NakaiAbstract:To evaluate the efficacy of long-term administration of Acyclovir as prophylaxis against varicella-zoster virus (VZV) reactivation, we analyzed the medical records of 86 consecutive adult patients who obtained engraftment after allogeneic hematopoietic stem cell transplantation from January 1996 to March 2000. We started long-term low-dose (400 mg/day) oral administration of Acyclovir in June 1999, and this was continued until the end of immunosuppressive therapy after transplantation. There was no breakthrough reactivation of VZV in patients receiving Acyclovir. Five patients who were receiving cyclosporine or prednisolone developed VZV reactivation after discontinuing Acyclovir. With this prophylaxis, the cumulative incidence of VZV reactivation at 1 year after transplantation decreased from 33% to 10% (P = 0.025). On multivariate analysis, the use of long-term Acyclovir was identified as a significant independent parameter for the development of VZV reactivation. These findings suggest the efficacy of long-term prophylaxis with low-dose Acyclovir. Resumption of Acyclovir upon restarting immunosuppressive therapy might be important for the further prevention of VZV reactivation. The benefit of long-term low-dose Acyclovir should be confirmed prospectively. Bone Marrow Transplantation (2001) 28, 689–692.
