Immunological Analysis of Treatment Interruption After Early Highly Active Antiretroviral Therapy

• Published in: Viral immunology Vol. 23; no. 6; pp. 69 - 618
• Main Authors: Schellens, Ingrid M.M., Pogany, Katalin, Westerlaken, Geertje H.A., Borghans, José A.M., Miedema, Frank, van Valkengoed, Irene G.M., Kroon, Frank P., Lange, Joep M.A., Brinkman, Kees, Prins, Jan M., van Baarle, Debbie
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.12.2010
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - immunology; Adaptive Immunity; Adolescent; Adult; Aged; Aged, 80 and over; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Drug therapy; Flow Cytometry; Health aspects; Highly active antiretroviral therapy; HIV infection; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immunity, Cellular; Longitudinal Studies; Lymphocyte Activation - immunology; Lymphocyte Count; Lymphokines - biosynthesis; Middle Aged; Physiological aspects; T cells; Viral Load; Withholding Treatment; Young Adult; Netherlands
• ISSN: 0882-8245; 1557-8976
• DOI: 10.1089/vim.2010.0062

We longitudinally evaluated HIV-specific T-cell immunity after discontinuation of highly active antiretroviral therapy (HAART). After treatment interruption (TI), some individuals could maintain a low plasma viral load (<15,000 copies/mL), whereas others could not (>50,000 copies/mL). Before HAART was initiated, plasma viral load was similar. After TI, the numbers of CD8 + T cells increased more in individuals without viral control, whereas individuals maintaining a low viral load showed a more pronounced increase in HIV-specific CD8 + T-cell numbers. No differences were seen in the number or percentage of cytokine-producing HIV-1-specific CD4 + T cells, or in proliferative capacity of T cells. Four weeks after TI, the magnitude of the total HIV-1-specific CD8 + T-cell response (IFN-γ + and/or IL-2 + and/or CD107a + ) was significantly higher in individuals maintaining viral control. Degranulation contributed more to the overall CD8 + T-cell response than cytokine production. Whether increased T-cell functionality is a cause or consequence of low viral load remains to be elucidated.