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Open AccessArticle

Clinical Infections by Herpesviruses in Patients Treated with Valproic Acid: A Nested Case-Control Study in the Spanish Primary Care Database, BIFAP

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BIFAP, Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Agency for Medicines and Medical Devices (AEMPS), 28022 Madrid, Spain
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Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Nicolás Cabrera 1, 28049 Madrid, Spain
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Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INA), 28040 Madrid, Spain
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Universidad Autónoma de Madrid, Departamento de Biología Molecular, Edificio de. Biología, Darwin 2, Cantoblanco, 28049 Madrid, Spain
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Universidad Autónoma de Madrid, Facultad de Medicina, Arzobispo Morcillo 4, 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(9), 1442; https://doi.org/10.3390/jcm8091442
Received: 6 August 2019 / Revised: 5 September 2019 / Accepted: 9 September 2019 / Published: 11 September 2019
(This article belongs to the Section Pharmacology)
The objective of this study is to evaluate the risk of clinical infections by herpesviruses in patients exposed to valproic acid (VPA). We performed a case-control study nested in a primary cohort selected from the Spanish primary care population-based research database BIFAP (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria) over the period 2001–2015. The events of interest were those diseases caused by any herpesviruses known to infect humans. For each case, up to 10 controls per case matched by age, gender, and calendar date were randomly selected. A conditional logistic regression was used to compute adjusted odds ratios (OR) and their 95% confidence intervals (95% CI). Current use of VPA was associated with a trend towards a reduced risk of clinical infections by herpesviruses as compared with non-users (OR 0.84; CI 95% 0.7–1.0; p = 0.057). Among current users, a trend to a decreased risk with treatment durations longer than 90 days was also observed. The results show a trend to a reduced risk of clinical infection by herpesviruses in patients exposed to VPA. These results are consistent with those in vitro studies showing that, in cultured cells, VPA can inhibit the production of the infectious progeny of herpesviruses. This study also shows the efficient use of electronic healthcare records for clinical exploratory research studies. View Full-Text
Keywords: BIFAP; valproic acid; herpesvirus infections; case-control study; electronic health care database BIFAP; valproic acid; herpesvirus infections; case-control study; electronic health care database
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Gil, M.; González-González, R.; Vázquez-Calvo, A.; Álvarez-Gutiérrez, A.; Martín-Acebes, M.A.; Praena, B.; Bello-Morales, R.; Saiz, J.-C.; López-Guerrero, J.A.; Tabarés, E.; Sobrino, F. Clinical Infections by Herpesviruses in Patients Treated with Valproic Acid: A Nested Case-Control Study in the Spanish Primary Care Database, BIFAP. J. Clin. Med. 2019, 8, 1442.

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