Associations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 with HIV disease progression in women

Howard Strickler, Melissa Fazzari, Andrea Kovacs, Carmen R. Isasi, Laura A. Napolitano, Howard Minkoff, Stephen Gange, Mary Young, Gerald B. Sharp, Robert C. Kaplan, Mardge Cohen, Marc J. Gunter, Tiffany G. Harris, Herbert Yu, Ellie Schoenbaum, Alan L. Landay, Kathryn Anastos

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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 (P trend = .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]; P trend = .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.

Original languageEnglish (US)
Pages (from-to)319-327
Number of pages9
JournalJournal of Infectious Diseases
Volume197
Issue number2
DOIs
StatePublished - Jan 15 2008

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Insulin-Like Growth Factor Binding Protein 3
Virus Diseases
Insulin-Like Growth Factor I
Disease Progression
HIV
Somatomedins
Highly Active Antiretroviral Therapy
CD4 Lymphocyte Count
Acquired Immunodeficiency Syndrome
T-Lymphocytes
Lymphocyte Count
Hematopoietic Stem Cells
Serum
human IGFBP3 protein
Confidence Intervals
Incidence
Growth

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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Associations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 with HIV disease progression in women. / Strickler, Howard; Fazzari, Melissa; Kovacs, Andrea; Isasi, Carmen R.; Napolitano, Laura A.; Minkoff, Howard; Gange, Stephen; Young, Mary; Sharp, Gerald B.; Kaplan, Robert C.; Cohen, Mardge; Gunter, Marc J.; Harris, Tiffany G.; Yu, Herbert; Schoenbaum, Ellie; Landay, Alan L.; Anastos, Kathryn.

In: Journal of Infectious Diseases, Vol. 197, No. 2, 15.01.2008, p. 319-327.

Research output: Contribution to journalArticle

Strickler, H, Fazzari, M, Kovacs, A, Isasi, CR, Napolitano, LA, Minkoff, H, Gange, S, Young, M, Sharp, GB, Kaplan, RC, Cohen, M, Gunter, MJ, Harris, TG, Yu, H, Schoenbaum, E, Landay, AL & Anastos, K 2008, 'Associations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 with HIV disease progression in women', Journal of Infectious Diseases, vol. 197, no. 2, pp. 319-327. https://doi.org/10.1086/524848
Strickler, Howard ; Fazzari, Melissa ; Kovacs, Andrea ; Isasi, Carmen R. ; Napolitano, Laura A. ; Minkoff, Howard ; Gange, Stephen ; Young, Mary ; Sharp, Gerald B. ; Kaplan, Robert C. ; Cohen, Mardge ; Gunter, Marc J. ; Harris, Tiffany G. ; Yu, Herbert ; Schoenbaum, Ellie ; Landay, Alan L. ; Anastos, Kathryn. / Associations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 with HIV disease progression in women. In: Journal of Infectious Diseases. 2008 ; Vol. 197, No. 2. pp. 319-327.
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AU - Fazzari, Melissa

AU - Kovacs, Andrea

AU - Isasi, Carmen R.

AU - Napolitano, Laura A.

AU - Minkoff, Howard

AU - Gange, Stephen

AU - Young, Mary

AU - Sharp, Gerald B.

AU - Kaplan, Robert C.

AU - Cohen, Mardge

AU - Gunter, Marc J.

AU - Harris, Tiffany G.

AU - Yu, Herbert

AU - Schoenbaum, Ellie

AU - Landay, Alan L.

AU - Anastos, Kathryn

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N2 - 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 (P trend = .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]; P trend = .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.

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