title: Immune resilience in HIV-infected individuals seronegative for cytomegalovirus.
abstract: OBJECTIVE
  Low CD4/CD8 T-cell ratios occur in conditions associated with reduced immune resilience, including older age and HIV infection. Effective antiretroviral therapy increases CD4/CD8 T-cell ratios, but often not to preinfection levels. The reasons for this deficit remain unclear. As cytomegalovirus (CMV) infection exacerbates falling CD4/CD8 T-cell ratios and immune senescence in the old elderly population, we investigated whether CMV infection is associated with refractory inversion of CD4/CD8 T-cell ratios and increased phenotypic evidence of immune senescence in HIV infection.
  
  
  METHODS
  An observational cohort study of HIV-infected individuals attending the Newfoundland and Labrador Provincial HIV Clinic in St. John's.
  
  
  METHODS
  CMV infection status was determined by ELISA with infected cell lysate. Expression of CD28 and CD57 on CD8 T cells and cellular immune responses against CMV were measured by flow cytometry. We compared CD4/CD8 T-cell ratios, percentage of CD8 T cells expressing CD28 and percentage of CD8 T cells expressing CD57 between groups of HIV-infected persons discordant for CMV infection.
  
  
  RESULTS
  The CMV-seronegative group had significantly higher CD4/CD8 T-cell ratios, more frequent normalization of the ratio to at least 1, and lesser phenotypic evidence of immune senescence.
  
  
  CONCLUSIONS
  CMV infection is associated with reduced immune reconstitution in HIV infection, even with suppression of HIV replication below detectable levels. This suggests that CMV infection, or some related factor, influences immune resilience in the setting of HIV infection.
authors.affiliation: aLaboratory of Immunoregulation, National Institute of Allergy and Infectious Disease, NIH, Bethesda, Maryland, USA bDivision of Infectious Diseases, Department of Medicine, Dalhousie University, Halifax, Nova Scotia cDivision of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Barrett
authors.forename: Staci N
authors.initials: SN
authors.lastname: Stapleton
authors.forename: Neva J
authors.initials: NJ
authors.lastname: Fudge
authors.forename: Michael D
authors.initials: MD
authors.lastname: Grant
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology*; D000328:Adult; D000375:Aging / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D016516:CD4-CD8 Ratio; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D010641:Phenotype