title: Safety of Switching Nevirapine Twice Daily to Nevirapine Once Daily in Virologically Suppressed Patients.
abstract: BACKGROUND
  The strategy of switching nevirapine (NVP) twice daily to once daily was evaluated.
  
  
  METHODS
  Forty-eight-week randomized, open, multicenter trial. Stable HIV-infected patients on NVP twice daily for >12-18 weeks with alanine aminotransferase (ALT) <2.5, the upper normal limit were randomized to continue their regimen or switch to NVP 400 mg once daily. Primary end point was the proportion of ALT/aspartate transaminase (AST) > or =grade 3.
  
  
  RESULTS
  Two hundred eighty-nine patients were included, mean CD4 620 cells per microliter. Noninferiority was demonstrated in the per protocol analysis, with 97.9% (once daily) and 99.3% (twice daily) of patients event free (difference, 1.4%; 95% confidence interval, -1.95% to 5.4%), whereas 81.8% vs. 93.8% were event free by intent-to-treat switch = toxicity analysis (difference, 12%; 95% confidence interval, 4.6% to 19.4%). Only 4 patients (3 once daily, 1 twice daily) had NVP-related grade 3/4 ALT/AST increases, but in 2 of them (once daily), transaminases decreased despite continuation with NVP. Two other once daily patients presented grade 3/4 ALT/AST increase due to well-documented acute hepatitis A virus or hepatitis C virus infection. Grade 2 ALT/AST increases occurred in 11.2% (once daily) vs. 10.3% (twice daily) of patients (P = 0.80). A larger number of once daily patients were lost to follow-up/violated protocol (15% vs. 5%).
  
  
  CONCLUSIONS
  In patients on standard twice daily NVP-containing regimens for at least 12-18 weeks, per protocol analysis showed that switching to once daily NVP was not inferior to continued twice daily NVP in terms of the predefined noninferiority margin of 10% for hepatotoxicity.
authors.affiliation: Hospital Universitari de Bellvitge, L'Hospitalet, Barcelona, Spain. dpodzamczer@csub.scs.es
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.forename: Montserrat
authors.initials: M
authors.lastname: Olmo
authors.forename: Jose
authors.initials: J
authors.lastname: Sanz
authors.forename: Vicente
authors.initials: V
authors.lastname: Boix
authors.forename: Eugenia
authors.initials: E
authors.lastname: Negredo
authors.forename: Hernando
authors.initials: H
authors.lastname: Knobel
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
authors.forename: Consuelo
authors.initials: C
authors.lastname: Vilades
authors.forename: Jose Hernandez
authors.initials: JH
authors.lastname: Quero
authors.forename: Lluis
authors.initials: L
authors.lastname: Force
authors.forename: Juan Gonzalez
authors.initials: JG
authors.lastname: Lahoz
authors.forename: Pepa
authors.initials: P
authors.lastname: Muñoz
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
authors.forename: Ana
authors.initials: A
authors.lastname: Mariño
authors.forename: Enrique
authors.initials: E
authors.lastname: Ortega
authors.forename: David
authors.initials: D
authors.lastname: Dalmau
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Esperanza
authors.initials: E
authors.lastname: Antón
authors.forename: Julio
authors.initials: J
authors.lastname: Sola
authors.forename: María J
authors.initials: MJ
authors.lastname: Galindo
authors.forename: Enric
authors.initials: E
authors.lastname: Pedrol
authors.forename: Jesus
authors.initials: J
authors.lastname: Sanz
authors.forename: Javier Torre de
authors.initials: JT
authors.lastname: Lima
authors.forename: Juan
authors.initials: J
authors.lastname: Flores
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001219:Aspartate Aminotransferases / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D015497:HIV-1; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase