title: Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection.
abstract: BACKGROUND
  Regimens containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimens containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection, but data from direct comparisons are limited.
  
  
  METHODS
  This randomized, double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1: zidovudine-lamivudine-abacavir, zidovudine-lamivudine plus efavirenz, and zidovudine-lamivudine-abacavir plus efavirenz.
  
  
  RESULTS
  We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log10 (71,434) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled. A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups. After a median follow-up of 32 weeks, 82 of 382 subjects in the triple-nucleoside group (21 percent) and 85 of 765 of those in the combined efavirenz groups (11 percent) had virologic failure; the time to virologic failure was significantly shorter in the triple-nucleoside group (P<0.001). This difference was observed regardless of the pretreatment HIV-1 RNA stratum (at least 100,000 copies per milliliter or below this level; P< or =0.001 for both comparisons). Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups.
  
  
  CONCLUSIONS
  In this trial of the initial treatment of HIV-1 infection, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides.
authors.affiliation: Weill Medical College of Cornell University, New York, USA. rgulick@med.cornell.edu
authors.forename: Roy M
authors.initials: RM
authors.lastname: Gulick
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Shikuma
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lustgarten
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Squires
authors.forename: William A
authors.initials: WA
authors.lastname: Meyer
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Schackman
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pilcher
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.forename: William E
authors.initials: WE
authors.lastname: Maher
authors.forename: Mallory D
authors.initials: MD
authors.lastname: Witt
authors.forename: Richard C
authors.initials: RC
authors.lastname: Reichman
authors.forename: Sally
authors.initials: S
authors.lastname: Snyder
authors.forename: Karin L
authors.initials: KL
authors.lastname: Klingman
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
mesh_terms: D000328:Adult; D000368:Aged; D000480:Alkynes; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000627:therapeutic use*; D010078:Oxazines / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D019259:Lamivudine; D009705:Nucleosides; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz