title: Metformin: a cheap and well-tolerated drug that provides benefits for viral infections.
abstract: OBJECTIVE
  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.
authors.affiliation: Unitat de Recerca Biomèdica (URB-CRB), IISPV, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain. jorge.joven@urv.cat
authors.forename: J
authors.initials: J
authors.lastname: Joven
authors.forename: J A
authors.initials: JA
authors.lastname: Menéndez
authors.forename: L
authors.initials: L
authors.lastname: Fernandez-Sender
authors.forename: E
authors.initials: E
authors.lastname: Espinel
authors.forename: A
authors.initials: A
authors.lastname: Rull
authors.forename: R
authors.initials: R
authors.lastname: Beltrán-Debón
authors.forename: E
authors.initials: E
authors.lastname: Rodríguez-Gallego
authors.forename: M
authors.initials: M
authors.lastname: Riera-Borrull
authors.forename: J
authors.initials: J
authors.lastname: Pedro-Botet
authors.forename: C
authors.initials: C
authors.lastname: Alonso-Villaverde
authors.forename: J
authors.initials: J
authors.lastname: Camps
authors.forename: G
authors.initials: G
authors.lastname: Aragonès
mesh_terms: D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D060085:Coinfection / Q000378:metabolism*; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007004:Hypoglycemic Agents; D025521:Tumor Suppressor Proteins; D008687:Metformin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases