title: Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy.
abstract: OBJECTIVE
  To evaluate the incidence, clinical features, and risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy.
  
  
  METHODS
  All cases of symptomatic mitochondrial toxicity reported in 416 patients participating in an open, randomized trial of peg-interferon alpha-2b plus ribavirin vs. interferon alpha-2b plus ribavirin for 48 weeks were reviewed. Associations with antiretroviral treatments and with clinical and laboratory findings were sought by univariate and multivariate analysis.
  
  
  RESULTS
  Eleven of the 383 patients who received at least 1 dose of anti-HCV treatment developed symptomatic mitochondrial toxicity (symptomatic hyperlactatemia and pancreatitis in 6 and 5 patients, respectively). All cases occurred in patients being treated for HIV infection, and the incidence of symptomatic mitochondrial toxicity was 47.5 per 1000 patient-years. In multivariate analysis, symptomatic mitochondrial toxicity was significantly associated with didanosine-containing antiretroviral regimens (odds ratio 46; 95% CI, 7.4 to infinity; P < 0.001), but not with stavudine or with nucleoside reverse transcriptase inhibitor regimens not containing didanosine. The incidence of symptomatic mitochondrial toxicity was 200.2 per 1000 patient-years in patients receiving didanosine. Demographic characteristics were not associated with symptomatic mitochondrial toxicity.
  
  
  CONCLUSIONS
  Coadministration of ribavirin with didanosine should be avoided. If unavoidable, patients should be monitored closely for mitochondrial toxicity. Didanosine should be suspended if clinical signs or symptoms of mitochondrial toxicity occur.
authors.affiliation: Groupe Hospitalier Universitaire Est, Université Paris 6, INSERM U444, France. firouze.bani-sadr@tnn.ap-hop-paris.fr
authors.forename: Firouzé
authors.initials: F
authors.lastname: Bani-Sadr
authors.forename: Fabrice
authors.initials: F
authors.lastname: Carrat
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: Ravy
authors.initials: R
authors.lastname: Hor
authors.forename: Eric
authors.initials: E
authors.lastname: Rosenthal
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.forename: Patrice
authors.initials: P
authors.lastname: Morand
authors.forename: Françoise
authors.initials: F
authors.lastname: Lunel-Fabiani
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon-Ceron
authors.forename: Lionel
authors.initials: L
authors.lastname: Piroth
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.forename: Michèle
authors.initials: M
authors.lastname: Bentata
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
authors.forename: Christian
authors.initials: C
authors.lastname: Perronne
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D015999:Multivariate Analysis; D010195:Pancreatitis / Q000139:chemically induced; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b