title: Cell-based measures of viral persistence are associated with immune activation and programmed cell death protein 1 (PD-1)-expressing CD4+ T cells.
abstract: BACKGROUND
  Studies aimed at defining the association between host immune responses and human immunodeficiency virus (HIV) persistence during therapy are necessary to develop new strategies for cure.
  
  
  METHODS
  We performed a comprehensive assessment of ultrasensitive plasma HIV RNA levels, cell-associated HIV RNA levels, proviral HIV DNA levels, and T cell immunophenotyping in a cohort of 190 subjects in whom HIV levels were suppressed by highly active antiretroviral therapy.
  
  
  RESULTS
  The median CD4(+) T cell count was 523 cells/mm(3), and the median duration of viral suppression was 31 months. Cell-associated RNA and proviral DNA levels (but not ultrasensitive plasma HIV RNA levels) were positively correlated with frequencies of CD4(+) and CD8(+) T cells expressing markers of T-cell activation/dysfunction (CD38, HLA-DR, CCR5, and/or programmed cell death protein 1 [PD-1]) (P < .05). Having a low CD4(+) T-cell count despite receipt of virologically suppressive therapy was associated with high cell-associated RNA and proviral DNA levels (P < .01) and higher frequencies of CD4(+) T cells expressing CD38, HLA-DR, CCR5, and/or PD-1 (P < .0001).
  
  
  CONCLUSIONS
  Cell-based measurements of viral persistence were consistently associated with markers of immune activation and the frequency of PD-1-expressing CD4(+) T cells. Treated patients with a low CD4(+) T-cell count had higher frequencies of PD-1-expressing CD4(+) T cells and cell-based measures of viral persistence, suggesting that HIV infection in these individuals may be more difficult to cure and may require unique interventions.
authors.affiliation: Department of Medicine, San Francisco General Hospital, 995 Potrero Ave, San Francisco, CA 94110, USA. hhatano@php.ucsf.edu
authors.forename: Hiroyu
authors.initials: H
authors.lastname: Hatano
authors.forename: Vivek
authors.initials: V
authors.lastname: Jain
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Tri D
authors.initials: TD
authors.lastname: Do
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hoh
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.forename: Frederick
authors.initials: F
authors.lastname: Hecht
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000187:drug effects; D005260:Female; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000097:blood*; D011533:Proviruses / Q000187:drug effects; D012367:RNA, Viral / Q000097:blood
chemical_list: D004279:DNA, Viral; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012367:RNA, Viral
keywords: 2-LTR circles; D-dimer; HIV; ongoing viral replication; raltegravir intensification