Associations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 with HIV disease progression in women.
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.
Strickler
Howard D
HD
Albert Einstein College of Medicine, Bronx, New York 10461, USA. strickle@aecom.yu.edu
Fazzari
Melissa
M
Kovacs
Andrea
A
Isasi
Carmen
C
Napolitano
Laura A
LA
Minkoff
Howard
H
Gange
Stephen
S
Young
Mary
M
Sharp
Gerald B
GB
Kaplan
Robert C
RC
Cohen
Mardge
M
Gunter
Marc J
MJ
Harris
Tiffany G
TG
Yu
Herbert
H
Schoenbaum
Ellie
E
Landay
Alan L
AL
Anastos
Kathryn
K
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
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I