Metformin: a cheap and well-tolerated drug that provides benefits for viral infections J Joven, 1 JA Menéndez, 2 L Fernandez-Sender, 1 E Espinel, 3 A Rull, 1 R Beltrán-Debón, 1 E Rodríguez-Gallego, 1 M Riera-Borrull, 1 J Pedro-Botet, 4 C Alonso-Villaverde, 5 J Camps 1 and G Aragonès 1 1 Unitat de Recerca Biomèdica (URB-CRB), IISPV, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain, 2 Catalan Institute of Oncology (ICO), Biomedical Research Institute (IdIBGi), Girona, Spain, 3 Hospital Universitari Vall d’Hebron, Barcelona, Spain, 4 Hospital Del Mar, Barcelona, Spain and 5 Hospital Son Llàtzer, Palma, Mallorca, Spain Objectives Insulin resistance in viral infections is common. We have explored the effectiveness of metformin for alleviating insulin resistance in HIV-infected patients and assessed the relevance of the ataxia-telangiectasia mutated (ATM) rs11212617 variant in the clinical response with the rationale that metformin modulates cellular bioenergetics in an ATM-dependent process. Methods HIV-infected patients (n = 385) were compared with controls recruited from the general population (n = 300) with respect to the genotype distribution of the ATM rs11212617 variant and its influence on selected metabolic and inflammatory variables. We also followed up a subset of male patients with HIV and hepatitis C virus (HCV) coinfection (n = 47) who were not receiving antiviral treatment and for whom metformin was prescribed for insulin resistance, which tends to have a higher incidence and severity in coinfected patients. Results Among the HIV-infected patients, human cytomegalovirus (91.9%) and HCV (62.3%) coinfections were frequent. Selected metabolic and/or inflammatory variables were significantly altered in infected patients. Treatment with metformin in HIV and HCV coinfected patients was well tolerated and significantly increased the sensitivity of peripheral tissues to insulin. The minor allele (C) of the rs11212617 variant was associated with treatment success and may affect the course of insulin resistance in response to metformin (odds ratio 1.21; 95% confidence interval 1.07–1.39; P = 0.005). There were no differences between treated and untreated patients in viral loads or variables measuring immune defence, indicating that toxicity is unlikely. Conclusions We provide novel data suggesting that identification of the ATM rs11212617 variant may be important in assessing the glycaemic response to metformin treatment for insulin resistance in HIV-infected patients. Keywords: AMP-activated protein kinase, HCV, HIV, insulin resistance, metabolism, rs11212617 ATM variant, viral hepatitis Accepted 7 October 2012 Introduction Viral nucleic acids integrate into the host genome via double-strand breaks (DSBs) in DNA and elicit an imme- diate DNA-damage response (DDR) through which accurate repair is achieved. This represents a genomic conflict Correspondence: Professor Jorge Joven, Unitat de Recerca Biomèdica (URB-CRB), IISPV, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain. Tel: 34 977 310 300; fax: 34 977 342 105; e-mail: jorge.joven@urv.cat DOI: 10.1111/hiv.12000 © 2012 British HIV Association HIV Medicine (2013), 14, 233–240 ORIGINAL RESEARCH 233