title: A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response.
abstract: BACKGROUND
  Some human immunodeficiency virus (HIV)-infected individuals are not able to achieve a normal CD4(+) T cell count despite prolonged, treatment-mediated viral suppression. We conducted an intensification study to assess whether residual viral replication contributes to replenishment of the latent reservoir and whether mucosal HIV-specific T cell responses limit the reservoir size.
  
  
  METHODS
  Thirty treated subjects with CD4(+) T cell counts of <350 cells/mm(3) despite viral suppression for ≥ 1 year were randomized to add raltegravir (400 mg twice daily) or matching placebo for 24 weeks. The primary end points were the proportion of subjects with undetectable plasma viremia (determined using an ultrasensitive assay with a lower limit of detection of <.3 copy/mL) and a change in the percentage of CD38(+)HLA-DR(+)CD8(+) T cells in peripheral blood mononuclear cells (PBMCs).
  
  
  RESULTS
  The proportion of subjects with undetectable plasma viremia did not differ between the 2 groups (P = .42). Raltegravir intensification did not have a significant effect on immune activation or HIV-specific responses in PBMCs or gut-associated lymphoid tissue.
  
  
  CONCLUSIONS
  Low-level viremia is not likely to be a significant cause of suboptimal CD4(+) T cell gains during HIV treatment.
  
  
  BACKGROUND
  NCT00631449.
authors.affiliation: University of California, San Francisco, USA. hhatano@php.ucsf.edu
authors.forename: Hiroyu
authors.initials: H
authors.lastname: Hatano
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Hayes
authors.forename: Viktor
authors.initials: V
authors.lastname: Dahl
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hoh
authors.forename: Harry
authors.initials: H
authors.lastname: Lampiris
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Sarah
authors.initials: S
authors.lastname: Palmer
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Shacklett
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis; D010919:Placebos / Q000008:administration & dosage; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000009:adverse effects; D000068898:Raltegravir Potassium; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D010919:Placebos; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1