Abstract
Background The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz. Methods In this multicentre, open-label, randomised trial, 1216 antiretroviral-therapy- naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log10 decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression [new Centers for Disease Control and Prevention grade C event or death], or change of allocated treatment). Analyses were by intention to treat. Findings Treatment failure occurred in 96 (43·6%) of 220 patients assigned nevirapine once daily, 169 (43·7%) of 387 assigned nevirapine twice daily, 151 (37·8%) of 400 assigned efavirenz, and 111 (53·1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5·9% (95% CI -0·9 to 12·8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0·193) or the increases in CD4-positive cells (p=0·800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine. Interpretation Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1253-1263 |
| Number of pages | 11 |
| Journal | Lancet |
| Volume | 363 |
| Issue number | 9417 |
| DOIs | |
| State | Published - Apr 17 2004 |
Funding
F van Leth has received travel grants and honoraria for presentations at symposia from Boehringer-Ingelheim. P Phanuphak has received honoraria from Bristol-Myers-Squibb as a scientific consultant and research grants from Bristol-Myers-Squibb, Hoffmann-LaRoche, GlaxoSmithKline, and Merck, Sharp and Dohme. K Ruxrungtham has received travel grants, grants, consultancy fees, and honoraria from various pharmaceutical companies including Hoffmann-LaRoche, Merck, Sharp and Dohme, Bristol-Myers-Squibb, and Abbott. S Miller has received consultancy fees from Bristol-Myers-Squibb and honoraria for presentations from Abbott and Boehringer-Ingelheim. B Gazzard has received travel grants, research grants, honoraria, and consultancy fees from various pharmaceutical companies including Boehringer-Ingelheim, Bristol-Myers-Squibb, GlaxoSmithKline, and Abbott Pharmaceuticals. P Cahn has received travel grants, grants, consultancy fees, and honoraria from various pharmaceutical companies including Shire, GlaxoSmithKline, Abbott, and Serono; he also has served as a consultant for Abbott and GlaxoSmithKline. I P van der Westhuizen has received consultancy fees from pharmaceutical companies. M A Johnson has received consultancy fees and lecture fees for presentations from Abbott, Bristol-Myers-Squibb, Hoffmann-LaRoche, and GlaxoSmithKline, and consultancy fees from Tibotec. F Mulcahy has received travel grants from GlaxoSmithKline and travel grants and honoraria for presentations at workshops from Bristol-Myers-Squibb, and he has also served as a consultant on the Advisory Board of Boehringer-Ingelheim. G C Levi has received lecture fees for presentations from Bristol-Myers-Squibb. G Reboredo has received travel grants and consultancy fees from various pharmaceutical companies including Bristol-Myers-Squibb, GlaxoSmithKline, and Hoffmann-LaRoche. K Squires has received consultancy fees and lecture fees for presentations from Gilead Science, Boehringer-Ingelheim, GlaxoSmithKline, and Abbott, and consultancy fees from Merck, Sharp and Dohme and Tibotec. F Raffi has received travel grants, grants, consultancy fees, and honoraria from various pharmaceutical companies including Abbott, Boehringer-Ingelheim, Bristol-Myers-Squibb, GlaxoSmithKline, and Hoffmann-LaRoche. C Katlama has received travel grants, grants, consultancy fees, and honoraria for presentations from Bristol-Myers-Squibb, GlaxoSmithKline, Boehringer-Ingelheim, Bayer, and Hoffmann-LaRoche. R Murphy has received consultancy fees from Boehringer-Ingelheim and Bristol-Myers-Squibb Pharmaceuticals. R van Leeuwen has received honoraria from various pharmaceutical companies including Boehringer-Ingelheim and Hoffmann-LaRoche. P Robinson is an employee of Boehringer-Ingelheim Pharmaceuticals company. F W Wit has received travel grants from Boehringer-Ingelheim, Abbott, Hoffmann-LaRoche, and GlaxoSmithKline, and honoraria for symposia from Boehringer-Ingelheim. J M A Lange has received consultancy fees and honoraria from GlaxoSmithKline, Boehringer-Ingelheim, Bristol-Myers-Squibb, Hoffmann-LaRoche, Merck, Sharp and Dohme, Schering-Plough, Bayer, Shire Pharmaceuticals, Agouron/Pfizer, and Virco/Tibotec.
ASJC Scopus subject areas
- General Medicine
