Browsing by Subject "Valacyclovir"

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    39. Viruses and Schizophrenia: Implications for Pathophysiology and Treatment
    (Oxford University Press, 2018-04) Breier, Alan; Psychiatry, School of Medicine
    Overall Abstract: The viral hypothesis of schizophrenia posits that viral infections disrupts cortical circuits that give rise to schizophrenia psychopathology. Prenatal viral exposure during key neurodevelopmental periods, either through direct effects on fetal brain or exposure to excessive maternal cytokines and other chemokines, have been implicated. In addition, abnormal activation of dormant neuro-viruses have been linked to the pathophysiology of schizophrenia. Activation of dormant viruses has potentially important treatment implication for therapies, such as valacyclovir, that suppress viral activity. Among the viruses that have been mostly frequently associated with schizophrenia include herpes simplex virus type 1 (HSV1) and Epstein-Barr virus (EBV). The purpose of this symposium is to focus on the role of viruses in the pathophysiology of schizophrenia and results of antiviral treatment trials in this illness.
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    A Double-Blind Trial of Adjunctive Valacyclovir to Improve Cognition in Early Phase Schizophrenia
    (Office of the Vice Chancellor for Research, 2015-04-17) Walters, Kamilah; Mehdiyoun, Nicole; Francis, Michael; Breier, Alan
    Schizophrenia is a chronic and debilitating neuropsychiatric disease that occurs in approximately one percent of the population and is characterized by cognitive deficits, including difficulties with abstract thinking, discerning reality from fiction, and communication. Cognitive deficits are a prominent feature of the illness and contribute to significant occupational and social disabilities. Additionally, there are no clinically effective treatments for cognitive deficits in schizophrenia. Although the etiology of these symptoms is unknown, recent studies have shown an association between Herpes Simplex Virus 1 (HSV-1) exposure and the severity of cognitive deficits in the schizophrenic population. Valacyclovir is an oral antiviral medication approved by the United States Food and Drug Administration for treatment of herpes virus infections, including HSV-1. Results from a pilot study at the University of Pittsburgh show that treatment with adjunctive valacyclovir improved working and visual memory in comparison to placebo in a population of older adults with chronic phase schizophrenia. The primary goal of the main study is to determine the efficacy of adjunctive valacyclovir to improve cognition by studying visual and working memory in HSV-1 positive early phase schizophrenia patients in a multi-site clinical trial coordinated by the Indiana University Psychotic Disorders Program. The aim of this research is to present a comprehensive review of recent findings regarding the importance of HSV-1 exposure and inflammatory markers in schizophrenia, and to discuss the methods and expected outcomes of our ongoing study.
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    Effect of Pritelivir Compared With Valacyclovir on Genital HSV-2 Shedding in Patients With Frequent Recurrences A Randomized Clinical Trial
    (AMA, 2016-12) Wald, Anna; Timmler, Burkhard; Magaret, Amalia; Warren, Terri; Tyring, Stephen; Johnston, Christine; Fife, Kenneth; Selke, Stacy; Huang, Meei-Li; Stobernack, Hans-Peter; Zimmerman, Holger; Corey, Lawrence; Birkmann, Alexander; Ruebsamen-Schaeff, Helga; Department of Medicine, School of Medicine
    Importance Current therapy of herpes infections relies on nucleoside analogues. Pritelivir is a well-tolerated novel herpes simplex virus (HSV) helicase-primase inhibitor that reduced genital shedding and lesions. Objective To compare the efficacy of pritelivir with valacyclovir for suppression of genital HSV-2 infection. Design, Setting, and Participants A phase 2, randomized, double-blind, crossover clinical trial at clinical research centers in 4 US cities (October 2012-July 2013) compared daily oral doses of 100 mg of pritelivir with 500 mg of valacyclovir. The planned sample size was 98 adults, allowing for detection of a 50% reduction in viral shedding between the study treatments. Healthy adults with 4 to 9 annual genital HSV-2 recurrences were eligible. Ninety-one participants were randomized: 45 to receive pritelivir and 46 to receive valacyclovir first when the US Food and Drug Administration placed the trial on clinical hold based on findings in a concurrent nonclinical toxicity study, and the sponsor terminated the study. Interventions Participants took the first drug for 28 days followed by 28 days of washout before taking the second drug for 28 days. Throughout treatment, the participants collected genital swabs 4 times daily for testing by HSV polymerase chain reaction assays. Main Outcomes and Measures The primary end point was within-participant genital HSV shedding while receiving pritelivir compared with valacyclovir. Secondary end points included the quantity of HSV in positive swabs and the frequency of genital lesions and shedding episodes. Results Of the 91 randomized participants (median age, 48 years; 57 women [63%]), 56 had completed both treatment periods at the time of the study’s termination. In intent-to-treat analyses, HSV shedding was detected in 2.4% (173 of 7276 ) of swabs during pritelivir treatment compared with 5.3% (392 of 7453) during valacyclovir treatment (relative risk [RR], 0.42; 95% CI, 0.21 to 0.82; P = .01). In swabs with HSV, the mean quantity of HSV was 3.2 log10 copies/mL during pritelivir treatment vs 3.7 log10 copies/mL during valacyclovir treatment (difference, −0.1; 95% CI, −0.6 to 0.5; P = .83). Genital lesions were present on 1.9% of days in the pritelivir group vs 3.9% in the valacyclovir group (RR, 0.40; 95% CI, 0.17-0.96; P = .04). The frequency of shedding episodes did not differ by group, with 1.3 per person-month for pritelivir and 1.6 per person-month for valacyclovir (RR, 0.80; 95% CI, 0.52 to 1.22; P = .29). Treatment-emergent adverse events occurred in 62.3% of participants in the pritelivir group and 69.2% of participants in the valacyclovir group. Conclusions and Relevance Among adults with frequently recurring genital HSV-2, the use of pritelivir compared with valacyclovir resulted in a lower percentage of swabs with HSV detection over 28 days. Further research is needed to assess longer-term efficacy and safety.