title: Early HIV RNA decay during raltegravir-containing regimens exhibits two distinct subphases (1a and 1b).
abstract: BACKGROUND
  We analyzed the early kinetics with integrase inhibitor treatment to gain new insights into viral dynamics.
  
  
  METHODS
  We analyzed data from 39 HIV-1 infected, treatment-naive, participants: 28 treated with raltegravir (RAL; multiple doses) monotherapy for 9 days, and 11 with RAL 400 mg twice daily and emtricitabine (200 mg daily)/tenofovir disoproxil fumarate (300 mg daily). Plasma HIV-1 RNA was measured frequently; the data was fitted using a mathematical model of viral dynamics distinguishing between infected cells with unintegrated HIV DNA and productively infected cells. Parameters were estimated using mixed-effect models.
  
  
  RESULTS
  RAL treatment led to a biphasic viral decline with a rapid first phase (1a) lasting approximately 5 days followed by a slower phase (1b). Phase 1a is attributed to the rapid elimination of productively infected cells. Phase 1b reflects the loss of infected cells with nonintegrated provirus due to cell loss and integration of HIV DNA. The half-lives of productively infected cells and of infected cells that had completed reverse transcription but had not yet integrated HIV DNA were approximately 19 h and between 3.6 and 5.8 days, respectively. The effectiveness of RAL in preventing proviral integration was 94% and 99.7%, for the combination therapy and monotherapy groups, respectively.
  
  
  CONCLUSIONS
  We found that the first phase of viral decay with RAL therapy was composed of two subphases corresponding to the half-lives of infected cells with integrated proviruses and with unintegrated HIV-DNA.
authors.affiliation: aThe Johns Hopkins University, Baltimore, Maryland, USA bINSERM, IAME, UMR 1137, and Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France cCenter for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts dUniversity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania eBrigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts fTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Andrade
authors.forename: Jeremie
authors.initials: J
authors.lastname: Guedj
authors.forename: Susan L
authors.initials: SL
authors.lastname: Rosenkranz
authors.forename: Darlene
authors.initials: D
authors.lastname: Lu
authors.forename: John
authors.initials: J
authors.lastname: Mellors
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.forename: Ruy M
authors.initials: RM
authors.lastname: Ribeiro
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D004279:DNA, Viral / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D010949:Plasma / Q000821:virology*; D012367:RNA, Viral / Q000097:blood*; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D000068898:Raltegravir Potassium