title: Associations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 with HIV disease progression in women.
abstract: BACKGROUND
  The insulin-like growth factor (IGF) axis has been hypothesized to influence the rate of human immunodeficiency virus (HIV) disease progression. This premise is based largely on laboratory models showing that IGF-I stimulates thymic growth and increases lymphocyte numbers and that IGF-binding protein (IGFBP)-3 has an opposing effect, inhibiting hematopoietic stem cell development.
  
  
  METHODS
  We studied 1422 HIV-infected women enrolled in a large cohort that entailed semiannual follow-up (initiated in 1994). Baseline serum samples were tested for IGF-I and IGFBP-3 to determine their associations with incident clinical acquired immunodeficiency syndrome (AIDS) and CD4+ T cell count decline prior to April 1996 (before the era of highly active antiretroviral therapy [HAART]).
  
  
  RESULTS
  Low IGF-I levels (Ptrend= .02) and high IGFBP-3 levels (Ptrend= .02) were associated with rapid CD4+ T cell count decline. Only IGFBP-3, however, was significantly associated with AIDS incidence (hazard ratio for highest vs. lowest quartile, 2.65 [95% confidence interval, 1.30-5.42]; Ptrend= .02) in multivariable models.
  
  
  CONCLUSIONS
  These findings suggest that serum levels of IGFBP-3 (and possibly IGF-I) are associated with the rate of HIV disease progression in women and, more broadly, that interindividual heterogeneity in the IGF axis may influence HIV pathogenesis. If correct, the IGF axis could be a target for interventions to slow HIV disease progression and extend the time before use of HAART becomes necessary.
authors.affiliation: Albert Einstein College of Medicine, Bronx, New York 10461, USA. strickle@aecom.yu.edu
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
authors.forename: Melissa
authors.initials: M
authors.lastname: Fazzari
authors.forename: Andrea
authors.initials: A
authors.lastname: Kovacs
authors.forename: Carmen
authors.initials: C
authors.lastname: Isasi
authors.forename: Laura A
authors.initials: LA
authors.lastname: Napolitano
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.forename: Stephen
authors.initials: S
authors.lastname: Gange
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Sharp
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
authors.forename: Mardge
authors.initials: M
authors.lastname: Cohen
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.forename: Tiffany G
authors.initials: TG
authors.lastname: Harris
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.forename: Ellie
authors.initials: E
authors.lastname: Schoenbaum
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
mesh_terms: D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D015994:Incidence; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016015:Logistic Models; D008875:Middle Aged; D016016:Proportional Hazards Models; D016387:Women's Health
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I