Safety of Switching Nevirapine Twice Daily to Nevirapine Once Daily in Virologically Suppressed Patients.
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.
Podzamczer
Daniel
D
Hospital Universitari de Bellvitge, L'Hospitalet, Barcelona, Spain. dpodzamczer@csub.scs.es
Olmo
Montserrat
M
Sanz
Jose
J
Boix
Vicente
V
Negredo
Eugenia
E
Knobel
Hernando
H
Domingo
Pere
P
Pineda
Juan A
JA
Vilades
Consuelo
C
Quero
Jose Hernandez
JH
Force
Lluis
L
Lahoz
Juan Gonzalez
JG
Muñoz
Pepa
P
Llibre
Josep M
JM
Mariño
Ana
A
Ortega
Enrique
E
Dalmau
David
D
Gatell
Josep M
JM
Antón
Esperanza
E
Sola
Julio
J
Galindo
María J
MJ
Pedrol
Enric
E
Sanz
Jesus
J
Lima
Javier Torre de
JT
Flores
Juan
J
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
D019380:Anti-HIV Agents; D019829:Nevirapine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase