title: Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study.
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 log(10) 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: International Antiviral Therapy Evaluation Center, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: van Leth
authors.forename: P
authors.initials: P
authors.lastname: Phanuphak
authors.forename: K
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: E
authors.initials: E
authors.lastname: Baraldi
authors.forename: S
authors.initials: S
authors.lastname: Miller
authors.forename: B
authors.initials: B
authors.lastname: Gazzard
authors.forename: P
authors.initials: P
authors.lastname: Cahn
authors.forename: U G
authors.initials: UG
authors.lastname: Lalloo
authors.forename: I P
authors.initials: IP
authors.lastname: van der Westhuizen
authors.forename: D R
authors.initials: DR
authors.lastname: Malan
authors.forename: M A
authors.initials: MA
authors.lastname: Johnson
authors.forename: B R
authors.initials: BR
authors.lastname: Santos
authors.forename: F
authors.initials: F
authors.lastname: Mulcahy
authors.forename: R
authors.initials: R
authors.lastname: Wood
authors.forename: G C
authors.initials: GC
authors.lastname: Levi
authors.forename: G
authors.initials: G
authors.lastname: Reboredo
authors.forename: K
authors.initials: K
authors.lastname: Squires
authors.forename: I
authors.initials: I
authors.lastname: Cassetti
authors.forename: D
authors.initials: D
authors.lastname: Petit
authors.forename: F
authors.initials: F
authors.lastname: Raffi
authors.forename: C
authors.initials: C
authors.lastname: Katlama
authors.forename: R L
authors.initials: RL
authors.lastname: Murphy
authors.forename: A
authors.initials: A
authors.lastname: Horban
authors.forename: J P
authors.initials: JP
authors.lastname: Dam
authors.forename: E
authors.initials: E
authors.lastname: Hassink
authors.forename: R
authors.initials: R
authors.lastname: van Leeuwen
authors.forename: P
authors.initials: P
authors.lastname: Robinson
authors.forename: F W
authors.initials: FW
authors.lastname: Wit
authors.forename: J M A
authors.initials: JM
authors.lastname: Lange
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D048588:Benzoxazines; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage* / Q000009:adverse effects; D010078:Oxazines / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz