Valtrex References

41: Antivir Ther. 2004 Jun;9(3):453-9.

Epstein-Barr virus load correlating with clinical manifestation and treatment response in a patient with angioimmunoblastic T-cell lymphoma.

Battegay M, Berger C, Rochlitz C, Hurwitz N, Hirsch HH, De Geyter C, Haque T, Nadal D.

Division of Infectious Diseases, Department of Internal Medicine & Research, University Hospital of Basel, Basel, Switzerland.

Epstein-Barr virus (EBV)-associated lymphoma may arise secondary to angioimmunoblastic T-cell lymphoma (AITL). The prognosis is poor despite chemotherapy and experimental therapies. We report on a 40-year-old woman with AITL without obvious immunodeficiency in which EBV-associated lymphoma developed. The occurrence and size of enlarged lymph nodes correlated strongly with the EBV load in serum (EBVL). Treatment with valacyclovir - Valtrex at the early stage resulted in a drastic more than 3 log10 decrease of EBVL and complete remission. However, valacyclovir - Valtrex had to be stopped after 6 months due to side effects, and the lymphoma reoccurred 3 months later associated with increasing EBVL. Eventually started cytotoxic chemo- and anti-CD20 therapy resulted only in partial remission. The lymphoma progressed and 33 months after it was diagnosed the patient died. This case report demonstrates the close association of EBVL and AITL and a beneficial effect of antiviral therapy at an initial stage of disease manifestation.

42: Clin Transplant. 2004 Jun;18(3):312-20.

A decision-analytic economic evaluation of valaciclovir prophylaxis for the prevention of cytomegalovirus infection and disease in renal transplantation.

Tilden DP, Chapman J, Davey PJ, Solly ML, Crowley S.

M-TAG, London, UK.

OBJECTIVE: This analysis evaluates the cost-effectiveness of valaciclovir prophylaxis using clinically and economically important health outcomes including graft failure, life-years, and quality-adjusted life-years (QALYs). METHODS: A Markov model was developed using a randomized, placebo-controlled trial of valaciclovir prophylaxis, together with a published epidemiological study and national renal transplant registry data. The model's population was stratified into two risk groups by donor/recipient cytomegalovirus (CMV) serostatus at transplantation: donor-positive/recipient-negative (D+R-) and recipient-positive (R+) patients. The model estimated costs and health outcomes over a 30-yr period from the perspective of Australian health care providers. RESULTS: The total health care cost was $3619 lower for D+R- patients receiving valaciclovir prophylaxis compared with those not receiving prophylaxis. D+R- patients receiving valaciclovir gained an extra 0.33 yr of life and 0.27 QALYs. R+ patients receiving valaciclovir prophylaxis gained an extra 0.07 yr of life and 0.05 QALYs, with an incremental cost of $914. This equates to $17 127 per QALY gained, which is highly cost-effective compared with other drugs and health interventions. CONCLUSIONS: Valaciclovir for the prophylaxis of CMV disease in renal transplant recipients is a cost-effective intervention, significantly reducing the burden of CMV disease to patients and health care providers.

43: Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):562-71.

Enhanced systemic T-cell activation after in situ gene therapy with radiotherapy in prostate cancer patients.

Satoh T, Teh BS, Timme TL, Mai WY, Gdor Y, Kusaka N, Fujita T, Pramudji CK, Vlachaki MT, Ayala G, Wheeler T, Amato R, Miles BJ, Kadmon D, Butler EB, Thompson TC.

Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA.

PURPOSE: In situ cytotoxic gene therapy can potentially trigger a systemic immune response, which could impact occult metastatic disease. We are currently conducting three clinical trials using in situ adenoviral vector mediated herpes simplex virus-thymidine kinase (HSV-tk) gene delivery followed by the HSV-tk prodrug ganciclovir (GCV) or valacyclovir - Valtrex (VCV). This study evaluates the systemic T-cell response after gene therapy in each trial. METHODS AND MATERIALS: The study protocol included three separate clinical trials in the Baylor Prostate Cancer SPORE Program: Trial A gene therapy in prostate cancer patients failing radiotherapy (36 patients), Trial B neoadjuvant gene therapy in pre-radical prostatectomy patients (22 patients), and Trial C gene therapy in combination with radiotherapy for prostate cancer (27 patients). Heparinized blood was collected at the time of vector injection and at selected intervals afterward. A complete blood count was performed, and peripheral blood lymphocytes were analyzed by fluorescent antibody cell sorting after labeling with dual color-labeled antibody pairs. RESULTS: The pretreatment mean percentage of activated CD8+ T cells (DR+CD8+ T cells) was 12.23%, 16.72%, and 14.09% (Trials A, B, and C, respectively). Two weeks posttreatment, this increased to 22.87%, 26.15%, and 39.04% (Trials A, B, and C, respectively), and these increases were statistically significant (p = 0.0188, p = 0.0010, p < 0.0001, respectively). The increase of DR+CD8+ T cells was significantly larger in Trial C than in Trial A (p = 0.0044) or Trial B (p = 0.0288). Total CD8+ T cells significantly increased at 2 weeks posttreatment in Trial B and C (p = 0.0013, p = 0.0004, respectively). Interestingly, only in Trial C were significant increases in activated CD4+ T cells seen at 2 weeks (p = 0.0035). CONCLUSIONS: This is the first report of systemic T-cell responses after HSV-tk+GCV/VCV gene therapy under three clinical trial conditions. There was an increase in activated CD8+ T cells in the peripheral blood after vector injection, suggesting the potential for activation of components of cell-mediated immune response in all trial conditions. The addition of radiotherapy to in situ gene therapy seems to further increase the total CD8+ T cells and activated CD4+ T cells.

44: J Antimicrob Chemother. 2004 Jun;53(6):899-901. Epub 2004 May 12.

Pharmacokinetics of valaciclovir.

MacDougall C, Guglielmo BJ.

Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA, USA.

While active against Herpesviridae, oral aciclovir is limited by low and inconsistent bioavailability. Modification of aciclovir by valine esterification, producing valaciclovir, results in significant increases in systemic aciclovir plasma levels. The exact mechanism of increased absorption with valaciclovir is not fully determined but probably involves intestinal dipeptide transporters, followed by rapid ester hydrolysis in the small intestine and liver. The enhanced pharmacokinetics of valaciclovir have translated into improvements in clinical efficacy and patient convenience.