title: Safety of etravirine in HIV-1/hepatitis B and/or C virus co-infected patients: pooled 96 week results from the Phase III DUET trials.
abstract: OBJECTIVE
  Human immunodeficiency virus (HIV)-infected patients are frequently co-infected with hepatitis B and/or C virus (HBV/HCV). The safety of etravirine was investigated over 96 weeks in patients co-infected with HIV type-1 (HIV-1) and HBV and/or HCV in the Phase III DUET trials. DUET-1 and DUET-2 are registered with clinicaltrials.gov (NCT00254046 and NCT00255099, respectively).
  
  
  METHODS
  Treatment-experienced, HIV-1-infected patients with documented non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance were randomized to receive either etravirine 200 mg or placebo, both twice daily plus a background regimen of darunavir/ritonavir, investigator-selected nucleoside reverse transcriptase inhibitors and optional enfuvirtide. Hepatitis co-infection status was confirmed by hepatitis B surface antigen or HCV antibody and qualitative HCV RNA. Co-infected patients were eligible if they did not require anti-hepatitis treatment and were clinically stable, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations <5× the upper limit of normal. Adverse events (AEs) and laboratory parameters were analysed.
  
  
  RESULTS
  Data were available for 566 etravirine- and 564 placebo-treated patients, of whom 72 (13%) and 68 (12%), respectively, were co-infected with HBV/HCV. Irrespective of co-infection status, the etravirine and placebo groups were comparable for the incidence of grade 3/4 AEs [co-infected: 31 (43%) versus 31 (46%) patients, respectively; non-co-infected: 200 (40%) versus 176 (35%), respectively] and serious AEs [co-infected: 25 (35%) versus 25 (37%), respectively; non-co-infected: 123 (25%) versus 119 (24%), respectively]. Consistent with the underlying hepatitis, relative to non-co-infected patients the co-infected patients, had a higher incidence of hepatic AEs [co-infected: 13 (18%) etravirine-treated versus 10 (15%) placebo-treated patients; non-co-infected: 36 (7%) versus 32 (6%), respectively], and grade 3/4 elevation of AST [co-infected: 8 (11%) versus 5 (7%), respectively; non-co-infected: 14 (3%) versus 9 (2%), respectively] and ALT [co-infected: 10 (14%) versus 6 (9%), respectively; non-co-infected: 14 (3%) versus 8 (2%), respectively]. Discontinuation due to hepatic AEs was low and comparable between the treatment groups, regardless of co-infection status (two co-infected patients in each treatment group; five etravirine-treated versus two placebo-treated non-co-infected patients).
  
  
  CONCLUSIONS
  Etravirine demonstrated a similar safety profile to placebo in the subgroup of patients co-infected with HIV and HBV and/or HCV in the DUET trials. The incidence and severity of AEs with etravirine was generally comparable to placebo irrespective of co-infection status.
authors.affiliation: Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. bclotet@irsicaixa.es
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Nathan
authors.initials: N
authors.lastname: Clumeck
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Steven
authors.initials: S
authors.lastname: Nijs
authors.forename: James
authors.initials: J
authors.lastname: Witek
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006514:Hepatitis B Surface Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000150:complications*; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008297:Male; D009570:Nitriles; D010919:Placebos / Q000008:administration & dosage; D011724:Pyridazines / Q000008:administration & dosage / Q000009:adverse effects*; D011743:Pyrimidines
chemical_list: D019380:Anti-HIV Agents; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D009570:Nitriles; D010919:Placebos; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine