title: Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV infection: a randomized, placebo-controlled trial.
abstract: BACKGROUND
  The degree to which human immunodeficiency virus (HIV) continues to replicate during antiretroviral therapy (ART) is controversial. We conducted a randomized, double-blind, placebo-controlled study to assess whether raltegravir intensification reduces low-level viral replication, as defined by an increase in the level of 2-long terminal repeat (2-LTR) circles.
  
  
  METHODS
  Thirty-one subjects with an ART-suppressed plasma HIV RNA level of <40 copies/mL and a CD4(+) T-cell count of ≥350 cells/mm(3) for ≥1 year were randomly assigned to receive raltegravir 400 mg twice daily or placebo for 24 weeks. 2-LTR circles were analyzed by droplet digital polymerase chain reaction at weeks 0, 1, 2, and 8.
  
  
  RESULTS
  The median duration of ART suppression was 3.8 years. The raltegravir group had a significant increase in the level of 2-LTR circles, compared to the placebo group. The week 1 to 0 ratio was 8.8-fold higher (P = .0025) and the week 2 to 0 ratio was 5.7-fold higher (P = .023) in the raltegravir vs. placebo group. Intensification also led to a statistically significant decrease in the D-dimer level, compared to placebo (P = .045).
  
  
  CONCLUSIONS
  Raltegravir intensification resulted in a rapid increase in the level of 2-LTR circles in a proportion of subjects, indicating that low-level viral replication persists in some individuals even after long-term ART. Intensification also reduced the D-dimer level, a coagulation biomarker that is predictive of morbidity and mortality among patients receiving treatment for HIV infection.
authors: Department of Medicine.
authors: Hiroyu
authors: H
authors: Hatano
authors: Matthew C
authors: MC
authors: Strain
authors: Rebecca
authors: R
authors: Scherzer
authors: Peter
authors: P
authors: Bacchetti
authors: Deborah
authors: D
authors: Wentworth
authors: Rebecca
authors: R
authors: Hoh
authors: Jeffrey N
authors: JN
authors: Martin
authors: Joseph M
authors: JM
authors: McCune
authors: James D
authors: JD
authors: Neaton
authors: Russell P
authors: RP
authors: Tracy
authors: Priscilla Y
authors: PY
authors: Hsue
authors: Douglas D
authors: DD
authors: Richman
authors: Steven G
authors: SG
authors: Deeks
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage*; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; C036309:fibrin fragment D; D000068898:Raltegravir Potassium
keywords: 2-LTR circles; D-dimer; HIV; ongoing viral replication; raltegravir intensification
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