Journal
AIDS
Volume 24, Issue 6, Pages 819-831Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0b013e3283367836
Keywords
acute infection; cytokines; disease progression; HIV-1; viral load
Categories
Funding
- Comprehensive International Program of Research on AIDS (CIPRA) of the Division of AIDS (DAIDS)
- National Institute of Allergy and infectious Disease (NIAID)
- National Institutes of Health (NIH) [D43TW00231]
- US Department of Health and Human Services (DHHS) [U19 AI51794]
- Center for HIV-AIDS Vaccine Immunology (CHAVI)
- Wellcome Trust
- Poliomyelitis Research Foundation (PRF) of South Africa
- Columbia University-Southern African Fogarty AIDS International Training and Research Programme (AITRP)
- Fogarty International Center
- South African Medical Research Council (MRC)
- PRF, KW Johnstone Research and Benfara
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Background: Both T-cell activation during early HIV-1 infection and soluble markers of immune activation during chronic infection are predictive of HIV disease progression. Although the acute phase of HIV infection is associated with increased pro-inflammatory cytokine production, the relationship between cytokine concentrations and HIV pathogenesis is unknown. Objectives: To identify cytokine biomarkers measurable in plasma during acute HIV-1 infection that predict HIV disease progression. Design: Study including 40 South African women who became infected with HIV-1 and were followed longitudinally from the time of infection. Methods: The concentrations of 30 cytokines in plasma from women with acute HIV-1 infection were measured and associations between cytokine levels and both viral load set point 12 months postinfection and time taken for CD4 cell counts to fall below 350 cells/mu l were determined using multivariate and Cox proportional hazards regression. Results: We found that the concentrations of five plasma cytokines, IL-12p40, IL-12p70, IFN-gamma, IL-7 and IL-15 in women with acute infection predicted 66% of the variation in viral load set point 12 months postinfection. IL-12p40, IL-12p70 and IFN-gamma were significantly associated with lower viral load, whereas IL-7 and IL-15 were associated with higher viral load. Plasma concentrations of IL-12p40 and granulocyte-macrophage colony-stimulating factor during acute infection were associated with maintenance of CD4 cell counts above 350 cells/mu l, whereas IL-1 alpha, eotaxin and IL-7 were associated with more rapid CD4 loss. Conclusion: A small panel of plasma cytokines during acute HIV-1 infection was predictive of long-term HIV disease prognosis in this group of South African women. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
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