title: Biological determinants of immune reconstitution in HIV-infected patients receiving antiretroviral therapy: the role of interleukin 7 and interleukin 7 receptor α and microbial translocation.
abstract: BACKGROUND
  Multiple host factors may influence CD4(+) T cell reconstitution in human immunodeficiency virus (HIV)-infected patients after suppressive antiretroviral therapy (ART). We hypothesized that residual immune activation and polymorphisms in the interleukin 7 (IL-7) receptor α (IL-7Rα) gene were important for immune recovery.
  
  
  METHODS
  We examined HIV-infected patients receiving suppressive ART (n = 96) for their IL-7Rα haplotypes and measured levels of lipopolysaccharide (LPS), soluble CD14, and IL-7 in plasma samples collected before and after ART initiation. Levels of soluble IL-7Rα were measured in HIV-infected patients with IL-7Rα haplotype 2 (n = 11) and those without IL-7Rα haplotype 2 (n = 22). Multivariate analysis was used to identify variables associated with faster recovery to CD4(+) T cell counts of >500 and >200 cells/μL.
  
  
  RESULTS
  Both LPS and soluble CD14 levels were significantly decreased with ART (P < .001, respectively) but remained elevated compared with uninfected controls. In a multivariate analysis, faster recovery to a CD4(+) T cell count of >500 cells/μL was significantly associated with higher baseline CD4(+) T cell count, younger age, lower pre-ART LPS level, higher pre-ART soluble CD14 level, lower pre-ART IL-7 level, and IL-7Rα haplotype 2 (hazard ratio, 1.50; 95% confidence interval, 1.03-2.19; P = .034). HIV-infected patients with haplotype 2 had significantly lower soluble IL-7Rα levels compared with those of patients without haplotype 2 (P < .001).
  
  
  CONCLUSIONS
  Both the extent of immune depletion prior to ART and IL-7Rα haplotype 2 are important determinants of time to CD4(+) T cell recovery to counts of >500 cells/μL.
authors.affiliation: Department of Medicine, Monash University, Burnet Institute, University of Melbourne, Melbourne, Australia.
authors.forename: Reena
authors.initials: R
authors.lastname: Rajasuriar
authors.forename: David
authors.initials: D
authors.lastname: Booth
authors.forename: Ajantha
authors.initials: A
authors.lastname: Solomon
authors.forename: Kyra
authors.initials: K
authors.lastname: Chua
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.forename: Maelenn
authors.initials: M
authors.lastname: Gouillou
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Schlub
authors.forename: Miles
authors.initials: M
authors.lastname: Davenport
authors.forename: Suzanne
authors.initials: S
authors.lastname: Crowe
authors.forename: Julian
authors.initials: J
authors.lastname: Elliott
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hoy
authors.forename: Christopher
authors.initials: C
authors.lastname: Fairley
authors.forename: Graeme
authors.initials: G
authors.lastname: Stewart
authors.forename: Paul
authors.initials: P
authors.lastname: Cameron
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D015851:Interleukin-7 / Q000097:blood / Q000276:immunology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000097:blood / Q000235:genetics / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D044966:Anti-Retroviral Agents; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides