title: Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV.
abstract: BACKGROUND
  Durable suppression of replication of the human immunodeficiency virus (HIV) depends on the use of potent, well-tolerated antiretroviral regimens to which patients can easily adhere.
  
  
  METHODS
  We conducted an open-label, noninferiority study involving 517 patients with HIV infection who had not previously received antiretroviral therapy and who were randomly assigned to receive either a regimen of tenofovir disoproxil fumarate (DF), emtricitabine, and efavirenz once daily (tenofovir-emtricitabine group) or a regimen of fixed-dose zidovudine and lamivudine twice daily plus efavirenz once daily (zidovudine-lamivudine group). The primary end point was the proportion of patients without baseline resistance to efavirenz in whom the HIV RNA level was less than 400 copies per milliliter at week 48 of the study.
  
  
  RESULTS
  Through week 48, significantly more patients in the tenofovir-emtricitabine group reached and maintained the primary end point of less than 400 copies of HIV RNA per milliliter than did those in the zidovudine-lamivudine group (84 percent vs. 73 percent, respectively; 95 percent confidence interval for the difference, 4 to 19 percent; P=0.002). This difference excludes the inferiority of the tenofovir DF, emtricitabine, and efavirenz regimen, indicating a significantly greater response with this regimen. Significant differences were also seen in the proportion of patients with HIV RNA levels of less than 50 copies per milliliter (80 percent in the tenofovir-emtricitabine group vs. 70 percent in the zidovudine-lamivudine group; 95 percent confidence interval for the difference, 2 to 17 percent; P=0.02) and in increases in CD4 cell counts (190 vs. 158 cells per cubic millimeter, respectively; 95 percent confidence interval for the difference, 9 to 55; P=0.002). More patients in the zidovudine-lamivudine group than in the tenofovir-emtricitabine group had adverse events resulting in discontinuation of the study drugs (9 percent vs. 4 percent, respectively; P=0.02). In none of the patients did the K65R mutation develop.
  
  
  CONCLUSIONS
  Through week 48, the combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efavirenz and proved superior in terms of virologic suppression, CD4 response, and adverse events resulting in discontinuation of the study drugs. (ClinicalTrials.gov number, NCT00112047.)
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. jgallant@jhmi.edu
authors.forename: Joel E
authors.initials: JE
authors.lastname: Gallant
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: José R
authors.initials: JR
authors.lastname: Arribas
authors.forename: Anton L
authors.initials: AL
authors.lastname: Pozniak
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Campo
authors.forename: Biao
authors.initials: B
authors.lastname: Lu
authors.forename: Damian
authors.initials: D
authors.lastname: McColl
authors.forename: Steven
authors.initials: S
authors.lastname: Chuck
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Enejosa
authors.forename: John J
authors.initials: JJ
authors.lastname: Toole
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Cheng
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D048588:Benzoxazines; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068679:Emtricitabine; D005260:Female; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use; D010078:Oxazines / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D000068698:Tenofovir; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D010078:Oxazines; D012367:RNA, Viral; D003841:Deoxycytidine; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C098320:efavirenz