Safety of Switching Nevirapine Twice Daily to Nevirapine Once Daily in Virologically Suppressed Patients
Por:
Podzamczer, D, Olmo, M, Sanz, J, Boix, V, Negredo, E, Knobel, H, Domingo, P, Pineda, JA, Vilades, C, Quero, JH, Force, L, Lahoz, JG, Munoz, P, Llibre, JM, Marino, A, Ortega, E, Dalmau, D, Gatell, JM, Anton, E, Sola, J, Galindo, MJ, Pedrol, E, Sanz, J, de Lima, JT, Flores, J
Publicada:
1 abr 2009
Resumen:
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) 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.
Filiaciones:
Podzamczer, D:
Hosp Univ Bellvitge, Infect Dis Serv, Barcelona 08907, Spain
Olmo, M:
Hosp Univ Bellvitge, Infect Dis Serv, Barcelona 08907, Spain
Sanz, J:
Hosp Principe Asturias, Madrid, Spain
Hosp La Princesa, Madrid, Spain
Boix, V:
Gen Hosp, Alicante, Spain
Negredo, E:
Hosp Germans Trias, Badalona, Spain
Knobel, H:
Hosp del Mar, Barcelona, Spain
Domingo, P:
Hos St Pau, Barcelona, Spain
Pineda, JA:
Hosp Valme, Seville, Spain
Vilades, C:
Hosp Joan 23, Tarragona, Spain
Quero, JH:
Hosp San Cecilio, Granada, Spain
Force, L:
Hosp Mataro, Mataro, Spain
Lahoz, JG:
Hosp Carlos 3, Madrid, Spain
Munoz, P:
Hosp Basurta, Basurta, Spain
Llibre, JM:
Hosp Calcella, Calcella, Spain
Marino, A:
Hosp Arquitecto Marcide, Ferrol, Spain
Ortega, E:
Hosp Gral Univ, Valencia, Spain
Dalmau, D:
Hosp Mutua, Terrassa, Spain
Gatell, JM:
Hosp Clin Barcelona, Barcelona, Spain
Sola, J:
Hosp Navarra, Navarra, Spain
Galindo, MJ:
Hosp Clin, Valencia, Spain
Pedrol, E:
Hosp Granollers, Granollers, Spain
Sanz, J:
Hosp Principe Asturias, Madrid, Spain
Hosp La Princesa, Madrid, Spain
de Lima, JT:
Hosp Costa del Sol, Marbella, Spain
Flores, J:
Hosp Arnau Vilanova, Valencia, Spain
|