title: Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection.
abstract: BACKGROUND
  Lopinavir is a newly developed inhibitor of human immunodeficiency virus (HIV) protease that, when formulated with ritonavir, yields mean trough plasma lopinavir concentrations that are at least 75 times as high as that needed to inhibit replication of wild-type HIV by 50 percent.
  
  
  METHODS
  We conducted a double-blind trial in which 653 HIV-infected adults who had not received antiretroviral therapy for more than 14 days were randomly assigned to receive either lopinavir-ritonavir (400 mg of lopinavir plus 100 mg of ritonavir twice daily) with nelfinavir placebo or nelfinavir (750 mg three times daily) with lopinavir-ritonavir placebo. All patients also received open-label stavudine and lamivudine. The primary efficacy end points were the presence of fewer than 400 HIV RNA copies per milliliter of plasma at week 24 and the time to the loss of virologic response through week 48.
  
  
  RESULTS
  At week 48, greater proportions of patients treated with lopinavir-ritonavir than of patients treated with nelfinavir had fewer than 400 copies of HIV RNA per milliliter (75 percent vs. 63 percent, P<0.001) and fewer than 50 copies per milliliter (67 percent vs. 52 percent, P<0.001). The time to the loss of virologic response was greater in the lopinavir-ritonavir group than in the nelfinavir group (hazard ratio, 2.0; 95 percent confidence interval, 1.5 to 2.7; P<0.001). The estimated proportion of patients with a persistent virologic response through week 48 was 84 percent for patients receiving lopinavir-ritonavir and 66 percent for those receiving nelfinavir. Both regimens were well tolerated, with the rate of discontinuation related to the study drugs at 3.4 percent among patients receiving lopinavir-ritonavir and 3.7 percent among patients receiving nelfinavir. Among patients with more than 400 copies of HIV RNA per milliliter at some point from week 24 through week 48, resistance mutations in HIV protease were demonstrated in viral isolates from 25 of 76 nelfinavir-treated patients (33 percent) and none of 37 patients treated with lopinavir-ritonavir (P<0.001).
  
  
  CONCLUSIONS
  For the initial treatment of HIV-infected adults, a combination regimen that includes lopinavir-ritonavir is well tolerated and has antiviral activity superior to that of a nelfinavir-containing regimen.
authors.affiliation: Toronto Hospital, University Health Network, University of Toronto, Toronto, ON, Canada. sharon.walmsley@uhn.on.ca
authors.forename: Sharon
authors.initials: S
authors.lastname: Walmsley
authors.forename: Barry
authors.initials: B
authors.lastname: Bernstein
authors.forename: Martin
authors.initials: M
authors.lastname: King
authors.forename: José
authors.initials: J
authors.lastname: Arribas
authors.forename: Gildon
authors.initials: G
authors.lastname: Beall
authors.forename: Peter
authors.initials: P
authors.lastname: Ruane
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.forename: David
authors.initials: D
authors.lastname: Johnson
authors.forename: Richard
authors.initials: R
authors.lastname: Lalonde
authors.forename: Anthony
authors.initials: A
authors.lastname: Japour
authors.forename: Scott
authors.initials: S
authors.lastname: Brun
authors.forename: Eugene
authors.initials: E
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000008:administration & dosage / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011744:Pyrimidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D018119:Stavudine / Q000008:administration & dosage / Q000627:therapeutic use; D016019:Survival Analysis; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019259:Lamivudine; D018119:Stavudine; D019888:Nelfinavir; D019438:Ritonavir