title: The effect of HIV infection and HAART on inflammatory biomarkers in a population-based cohort of women.
abstract: OBJECTIVE
  HIV causes inflammation that can be at least partially corrected by HAART. To determine the qualitative and quantitative nature of cytokine perturbation, we compared cytokine patterns in three HIV clinical groups, including HAART responders (HAART), untreated HIV noncontrollers, and HIV-uninfected (NEG).
  
  
  METHODS
  Multiplex assays were used to measure 32 cytokines in a cross-sectional study of participants in the Women's Interagency HIV Study. Participants from three groups were included: HAART (n = 17), noncontrollers (n = 14), and HIV NEG (n = 17).
  
  
  RESULTS
  Several cytokines and chemokines showed significant differences between noncontrollers and NEG participants, including elevated interferon gamma-induced 10 (IP-10) and tumor necrosis factor-α (TNF-α) and decreased interleukin-12(p40) [IL-12(p40)], IL-15, and fibroblast growth factor-2 (FGF-2) in noncontroller participants. Biomarker levels among HAART women more closely resembled the NEG, with the exception of TNF-α and FGF-2. Secondary analyses of the combined HAART and noncontroller groups revealed that IP-10 showed a strong, positive correlation with viral load and negative correlation with CD4(+) T-cell counts. The growth factors vascular endothelial growth factor, epidermal growth factor, and FGF-2 all showed a positive correlation with increased CD4(+) T-cell counts.
  
  
  CONCLUSIONS
  Untreated, progressive HIV infection was associated with decreased serum levels of cytokines important in T-cell homeostasis (IL-15) and T-cell phenotype determination (IL-12), and increased levels of innate inflammatory mediators such as IP-10 and TNF-α. HAART was associated with cytokine profiles that more closely resembled those of HIV-uninfected women. The distinctive pattern of cytokine levels in the three study groups may provide insights into HIV pathogenesis, and responses to therapy.
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, USA.
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Keating
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Golub
authors.forename: Marek
authors.initials: M
authors.lastname: Nowicki
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Howard
authors.initials: H
authors.lastname: Crystal
authors.forename: Mardge H
authors.initials: MH
authors.lastname: Cohen
authors.forename: Jinbing
authors.initials: J
authors.lastname: Zhang
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Greenblatt
authors.forename: Seema
authors.initials: S
authors.lastname: Desai
authors.forename: Shiquan
authors.initials: S
authors.lastname: Wu
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D054357:Chemokine CXCL10 / Q000097:blood / Q000187:drug effects; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007249:Inflammation / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood; D019409:Interleukin-15 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects; D019562:Viral Load / Q000187:drug effects
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; D016207:Cytokines; D019409:Interleukin-15; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D018664:Interleukin-12