title: Impact of treatment with raltegravir during primary or chronic HIV infection on RNA decay characteristics and the HIV viral reservoir.
abstract: BACKGROUND
  Eradication of HIV-1 is prevented by the formation of viral reservoirs in peripheral blood, lymphoid tissues and other sanctuary sites. In most patients, rebound upon treatment cessation is prompt. We assessed whether early treatment with raltegravir can impact on the formation of the viral reservoir.
  
  
  METHODS
  We conducted an open-label, nonrandomized study, and assessed in detail the decay characteristics of HIV-1 RNA in plasma, HIV DNA in CD4 T cells and colon tissue biopies (CTBs) in 16 treatment-naive patients during either primary (PHI, n = 8) or chronic (CHI, n = 8) HIV-1 infection after treatment with raltegravir and Truvada for 52 weeks.
  
  
  RESULTS
  HIV-1 RNA decreased rapidly with treatment in all patients; first and second phase levels were lower in PHI patients with no appreciable difference in residual viremia between the two groups at 52 weeks. Episomal HIV-1 DNA increased sharply in both groups with peak levels at 3-4 weeks. Total HIV-1 DNA levels were reduced in both groups with similar kinetics, but were markedly lower in PHI patients after 52 weeks. Integrated HIV-1 DNA levels were significantly lower at baseline in PHI patients and this difference widened on treatment. Finally, total HIV-1 DNA decayed substantially in both groups in CTB.
  
  
  CONCLUSIONS
  Treatment with raltegravir resulted in a large number of abrogated integration events, reflected by the increase of episomal HIV-1 DNA after treatment initiation. Levels of total and integrated HIV-1 DNA were lower in PHI patients at the end of the study period.
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia. k.koelsch@amr.org.au
authors.forename: Kersten K
authors.initials: KK
authors.lastname: Koelsch
authors.forename: Christoph
authors.initials: C
authors.lastname: Boesecke
authors.forename: Kristin
authors.initials: K
authors.lastname: McBride
authors.forename: Linda
authors.initials: L
authors.lastname: Gelgor
authors.forename: Paul
authors.initials: P
authors.lastname: Fahey
authors.forename: Ven
authors.initials: V
authors.lastname: Natarajan
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.forename: Mark
authors.initials: M
authors.lastname: Bloch
authors.forename: John M
authors.initials: JM
authors.lastname: Murray
authors.forename: John
authors.initials: J
authors.lastname: Zaunders
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001315:Australia / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011760:Pyrrolidinones / Q000494:pharmacology*; D012367:RNA, Viral / Q000032:analysis / Q000187:drug effects; D000068898:Raltegravir Potassium; D017423:Sequence Analysis, RNA; D019562:Viral Load / Q000187:drug effects; D017735:Virus Latency / Q000187:drug effects* / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium