title: Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE): a randomised, open-label, non-inferiority study.
abstract: BACKGROUND
  Uncertainty exists about the best treatment for people with HIV-1 who have virological failure with first-line combination antiretroviral therapy of a non-nucleoside analogue (NNRTI) plus two nucleoside or nucleotide analogue reverse transcriptase inhibitors (NtRTI). We compared a second-line regimen combining two new classes of drug with a WHO-recommended regimen.
  
  
  METHODS
  We did this 96-week, phase 3b/4, randomised, open-label non-inferiority trial at 37 sites worldwide. Adults with HIV-1 who had confirmed virological failure (plasma viral load >500 copies per mL) after 24 weeks or more of first-line treatment were randomly assigned (1:1) to receive ritonavir-boosted lopinavir plus two or three NtRTIs (control group) or ritonavir-boosted lopinavir plus raltegravir (raltegravir group). The randomisation sequence was computer generated with block randomisation (block size four). Neither participants nor investigators were masked to allocation. The primary endpoint was the proportion of participants with plasma viral load less than 200 copies per mL at 48 weeks in the modified intention-to-treat population, with a non-inferiority margin of 12%. This study is registered with ClinicalTrials.gov, number NCT00931463.
  
  
  RESULTS
  We enrolled 558 patients, of whom 541 (271 in the control group, 270 in the raltegravir group) were included in the primary analysis. At 48 weeks, 219 (81%) patients in the control group compared with 223 (83%) in the raltegravir group met the primary endpoint (difference 1·8%, 95% CI -4·7 to 8·3), fulfilling the criterion for non-inferiority. 993 adverse events occurred in 271 participants in the control group versus 895 in 270 participants in the raltegravir group, the most common being gastrointestinal.
  
  
  CONCLUSIONS
  The raltegravir regimen was no less efficacious than the standard of care and was safe and well tolerated. This simple NtRTI-free treatment strategy might extend the successful public health approach to management of HIV by providing simple, easy to administer, effective, safe, and tolerable second-line combination antiretroviral therapy.
  
  
  BACKGROUND
  University of New South Wales, Merck, AbbVie, the Foundation for AIDS Research.
authors.forename: M A
authors.initials: MA
authors.lastname: Boyd
authors.forename: N
authors.initials: N
authors.lastname: Kumarasamy
authors.forename: C L
authors.initials: CL
authors.lastname: Moore
authors.forename: C
authors.initials: C
authors.lastname: Nwizu
authors.forename: M H
authors.initials: MH
authors.lastname: Losso
authors.forename: L
authors.initials: L
authors.lastname: Mohapi
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Kerr
authors.forename: A H
authors.initials: AH
authors.lastname: Sohn
authors.forename: H
authors.initials: H
authors.lastname: Teppler
authors.forename: O
authors.initials: O
authors.lastname: Van de Steen
authors.forename: J-M
authors.initials: JM
authors.lastname: Molina
authors.forename: S
authors.initials: S
authors.lastname: Emery
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage*; D008297:Male; D009705:Nucleosides / Q000008:administration & dosage; D009711:Nucleotides / Q000008:administration & dosage; D011760:Pyrrolidinones / Q000008:administration & dosage*; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009705:Nucleosides; D009711:Nucleotides; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D000068898:Raltegravir Potassium; D019438:Ritonavir