title: Restoration of CMV-specific-CD4 T cells with ART occurs early and is greater in those with more advanced immunodeficiency.
abstract: OBJECTIVE
  Restoration of Cytomegalovirus-specific-CD4 T cell (CMV-Sp-CD4) responses partly accounts for the reduction of CMV-disease with antiretroviral-therapy (ART), but CMV-Sp-CD4 may also drive immune activation and immunosenescence. This study characterized the dynamics of CMV-Sp-CD4 after ART initiation and explored associations with CD4 T cell recovery as well as frequency of naïve CD4 T cells at week 96.
  
  
  METHODS
  Fifty HIV-infected, ART-naïve Thai adults with CD4 T cell count ≤ 350 cells/µL and starting ART were evaluated over 96 weeks (ClinicalTrials.gov identifier NCT01296373). CMV-Sp-CD4 was detected by co-expression of CD25/CD134 by flow cytometry after CMV-antigen stimulation.
  
  
  RESULTS
  All subjects were CMV sero-positive, 4 had quantifiable CMV-DNA (range 2.3-3.9 log10 copies/mL) at baseline but none had clinically apparent CMV-disease. Baseline CMV-Sp-CD4 response was positive in 40 subjects. Those with CD4 T cell count < 100 cells/µL were less likely to have positive baseline CMV-Sp-CD4 response (P=0.003). Positive baseline CMV-Sp-CD4 response was associated with reduced odds of quantifiable CMV-DNA (P=0.022). Mean CD4 T cell increase at week 96 was 213 cells/µL. This was associated positively with baseline HIV-VL (P=0.001) and negatively with age (P=0.003). The frequency of CMV-Sp-CD4 increased at week 4 (P=0.008), then declined. Those with lower baseline CMV-Sp-CD4 (P=0.009) or CDC category C (P<0.001) had greater increases in CMV-Sp-CD4 at week 4. At week 96, CD4 T cell count was positively (P<0.001) and the frequency of CMV-Sp-CD4 was negatively (P=0.001) associated with the percentage of naïve CD4 T cells.
  
  
  CONCLUSIONS
  Increases in CMV-Sp-CD4 with ART occurred early and were greater in those with more advanced immunodeficiency. The frequency of CMV-Sp-CD4 was associated with reduced naïve CD4 T cells, a marker associated with immunosenescence.
authors.affiliation: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia ; HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Hsu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.forename: Thatri
authors.initials: T
authors.lastname: Iampornsin
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Pett
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.forename: Parawee
authors.initials: P
authors.lastname: Thongpaeng
authors.forename: John J
authors.initials: JJ
authors.lastname: Zaunders
authors.forename: Sasiwimol
authors.initials: S
authors.lastname: Ubolyam
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003587:Cytomegalovirus / Q000187:drug effects / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D044966:Anti-Retroviral Agents