title: Randomized trial of time-limited interruptions of protease inhibitor-based antiretroviral therapy (ART) vs. continuous therapy for HIV-1 infection.
abstract: BACKGROUND
  The clinical outcomes of short interruptions of PI-based ART regimens remains undefined.
  
  
  METHODS
  A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load <50 copies/ml and CD4 T cell count >450 cells/µl on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count >350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints.
  
  
  RESULTS
  The proportions of CD4 counts >350 cells/µl were 82.12% for the intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2-sided CI: -0.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm.
  
  
  CONCLUSIONS
  We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00100646.
authors: Clinical HIV Research Unit, Faculty of Health Sciences, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
authors: Cynthia
authors: C
authors: Firnhaber
authors: Livio
authors: L
authors: Azzoni
authors: Andrea S
authors: AS
authors: Foulkes
authors: Robert
authors: R
authors: Gross
authors: Xiangfan
authors: X
authors: Yin
authors: Desiree
authors: D
authors: Van Amsterdam
authors: Doreen
authors: D
authors: Schulze
authors: Deborah K
authors: DK
authors: Glencross
authors: Wendy
authors: W
authors: Stevens
authors: Gillian
authors: G
authors: Hunt
authors: Lynn
authors: L
authors: Morris
authors: Lawrence
authors: L
authors: Fox
authors: Ian
authors: I
authors: Sanne
authors: Luis J
authors: LJ
authors: Montaner
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D019259:Lamivudine / Q000627:therapeutic use; D061466:Lopinavir / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D018119:Stavudine; D019438:Ritonavir