title: Prospective, open-label comparative study of liver toxicity in an unselected population of HIV-infected patients treated for the first time with efavirenz or nevirapine.
abstract: OBJECTIVE
  To compare the two nonnucleoside reverse transcriptase inhibitors (NNRTIs) when first introduced in an antiretroviral regimen, a prospective open-label assessment of the frequency, severity, risk factors, and outcome of hepatotoxicity was performed.
  
  
  METHODS
  Liver enzymes were followed-up during 18 months in patients who received efavirenz (EFV; 324 patients) or nevirapine (NVP; 299).
  
  
  RESULTS
  The two study groups were comparable, except for the lower baseline CD4+ count found in the EFV group. No differences were found when considering the type and duration of eventual prior anti-HIV therapy; frequency and length of protease inhibitors, methadone, or anti-tubercular drug use; HCV-HBV co-infection; other hepatobiliary disorders; and alcohol-drug abuse. The frequency of overall and first-month drug interruption proved similar in the two study groups. A hepatotoxicity characterized by at least a 2-fold increase of transaminases versus baseline was significantly linked with NVP, and the number of patients showing hepatotoxicity tended to a reduction in the EFV group. Also the time to peak transaminase alterations was shorter in the NVP group. All significant differences regarding liver-pancreatic toxicities were controlled per eventual baseline hepatobiliary-pancreatic diseases, HIV stage, and concurrent drug therapies.
  
  
  CONCLUSIONS
  Hepatotoxicity is a significant concern in the setting of antiretroviral-treated HIV disease. NVP-based HAART may be more hepatotoxic than EFV-based HAART, and a role is played by chronic liver disorders. Although concurrent hepatobiliary disorders and the possible hepatotoxicity of antiretrovirals do not represent contraindications to nonnucleoside inhibitor use, strict monitoring is recommended.
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Infectious Diseases, University of Bologna Alma Mater Studiorum, S. Orsola Hospital, Bologna, Italy. manfredi@med.unibo.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Manfredi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Calza
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiodo
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury; D002802:Cholinesterases / Q000097:blood; D015331:Cohort Studies; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology; D008297:Male; D019829:Nevirapine / Q000009:adverse effects* / Q000627:therapeutic use; D010078:Oxazines / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012709:Serum Albumin / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D012709:Serum Albumin; D019829:Nevirapine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002802:Cholinesterases; D000469:Alkaline Phosphatase; C098320:efavirenz