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

Howard D. Strickler, Melissa Fazzari, Andrea Kovacs, Carmen 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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9 Scopus citations

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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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Strickler, H. D., Fazzari, M., Kovacs, A., Isasi, C., Napolitano, L. A., Minkoff, H., Gange, S., Young, M., Sharp, G. B., Kaplan, R. C., Cohen, M., Gunter, M. J., Harris, T. G., Yu, H., Schoenbaum, E., Landay, A. L., & 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, 197(2), 319-327. https://doi.org/10.1086/524848