Associations of Insulin-Like Growth Factor (IGF)–I and IGF-Binding Protein–3 with HIV Disease Progression in Women
1Albert Einstein College of Medicine, Bronx, and 2Maimonides Medical Center, Brooklyn, New York; 3University of Southern California, Los Angeles, and 4Gladstone Institute of Virology and Immunology, University of California, San Francisco; 5Johns Hopkins University, Baltimore, and 6Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 7Georgetown University, Washington, DC; 8John H. Stroger Hospital of Cook County and Rush University Medical Center, Chicago, Illinois; 9Yale University, New Haven, Connecticut
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 (
) and high IGFBP-3 levels (
) 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]; 
) 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.
Received 2 May 2007; accepted 6 August 2007; electronically published 4 January 2008.
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Potential conflicts of interest: none reported.
Financial support: Center for AIDS Research at the Albert Einstein College of Medicine and the Montefiore Medical Center, funded by the National Institutes of Health (grant AI-51519). Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (principal investigators) at the New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); the Washington, DC, Metropolitan Consortium (Mary Young); the Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); the Los Angeles County/Southern California Consortium (Alexandra Levine); the Chicago Consortium (Mardge Cohen); and the Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases, with supplemental funding from the National Cancer Institute and the National Institute on Drug Abuse (grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590). Funding was also provided by the National Institute of Child Health and Human Development (grant UO1-HD-32632) and the National Center for Research Resources (grants MO1-RR-00071, MO1-RR-00079, and MO1-RR-00083).