Background:  Liver toxicity has been observed in naive pts initiating a once-daily nevirapine (NVP) -containing HAART regimen. The objective of this study was to compare hepatotoxicity, other safety parameters and efficacy in stable patients tolerating a standard twice-daily NVP regimen who switched to once-daily NVP.

Methods:  This was a 12-month randomized, open, multicenter trial enrolling patients under NVP-twice-daily-containing HAART regimens for >12 weeks (>18 weeks in women with CD4 >250 cells/µL) with undetectable viral load and alanine aminotransferase (ALT) <2.5 times the upper limit of normality. Patients stratified by CD4 cell count and hepatitis C virus (HCV) status, were randomized to continue, or switch to NVP 400 mg once daily. Primary end-point was time to ALT or aspartate aminotransferase (AST) grade ³3 (modified ACTG criteria >5 times upper limit of normality if normal at baseline or >3.5 times above baseline if baseline values greater than upper limit of normality). Intent-to treat switch = toxicity (S=T) and observed data analyses were performed.

Results:  We randomized 302 patients and 289 were considered evaluable (143 once daily and 146 twice daily). No statistically significant differences were observed in baseline characteristics between arms:  71% were men, 97% Caucasian, 31% former drug users, 30% had AIDS, and 33% were HCV⁺ and CD4 620 cells/µL. Median previous time under twice-daily NVP was 43 (3 to 93) months; 82% (once-daily) vs 94% (twice-daily) patients had no events during follow-up by intent to treat S=T analysis (Log rank p = 0.002), while no differences were found in the observed data analysis (98% vs 99%, p = 0.27). Only 6 patients (5 once daily, 1 twice daily) had grade-3 and -4 ALT or AST increase during follow-up. Of the 5 once-daily patients, transaminase increase in 2 was related to well-documented acute hepatitis A virus (HAV) and HCV, and in other 2 patients, ALT/AST levels decreased despite continuation with NVP. Grade-2 to -4 ALT or AST increase was observed in 15% (once-daily) vs 11% (twice-daily) (p = 0.38). Virologic failure was observed in 4 once-daily and 3 twice-daily patients. Lost to follow-up, protocol violation, or switch for other reasons occurred in more once-daily patients (15% vs 5%).

Conclusions:  In patients under standard NVP-containing regimens for at least 12 to 18 weeks, switching to a once-daily NVP regimen is associated with a low frequency of hepatotoxicity while viral suppression is mantained.