Relationship between T Cell Activation and CD4+ T Cell Count in HIV-Seropositive Individuals with Undetectable Plasma HIV RNA Levels in the Absence of Therapy

• Published in: The Journal of infectious diseases Vol. 197; no. 1; pp. 126 - 133
• Main Authors: Hunt, Peter W., Brenchley, Jason, Sinclair, Elizabeth, McCune, Joseph M., Roland, Michelle, Shafer, Kimberly Page, Hsue, Priscilla, Emu, Brinda, Krone, Melissa, Lampiris, Harry, Douek, Daniel, Martin, Jeffrey N., Deeks, Steven G.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-01-2008; University of Chicago Press
• Subjects: Adult; AIDS; Antiretrovirals; Biological and medical sciences; Blood plasma; CD4 Lymphocyte Count; Cohort Studies; Female; Fundamental and applied biological sciences. Psychology; HIV; HIV 1; HIV infections; HIV Infections - immunology; HIV Seropositivity - immunology; HIV-1 - immunology; HIV/AIDS; Humans; Infections; Lymphocyte Activation; Male; Microbiology; Middle Aged; Miscellaneous; RNA; RNA, Viral - blood; T lymphocytes; T-Lymphocytes - immunology; T-Lymphocytes - virology; Viremia; Viremia - immunology; Virology; Virus; Retroviridae; Treatment; Human immunodeficiency virus; Lentivirus; T-Lymphocyte
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/524143

Background. Although untreated human immunodeficiency virus (HIV)-infected patients maintaining undetectable plasma HIV RNA levels (elite controllers) have high HIV-specific immune responses, it is unclear whether they experience abnormal levels of T cell activation, potentially contributing to immunodeficiency. Methods. We compared percentages of activated (CD38+HLA-DR+) T cells between 30 elite controllers, 47 HIV-uninfected individuals, 187 HIV-infected individuals with undetectable viremia receiving antiretroviral therapy (antiretroviral therapy suppressed), and 66 untreated HIV-infected individuals with detectable viremia. Because mucosal translocation of bacterial products may contribute to T cell activation in HIV infection, we also measured plasma lipopolysaccharide (LPS) levels. Results. Although the median CD4+ cell count in controllers was 727 cells/mm3, 3 (10%) had CD4+ cell counts <350 cells/mm3 and 2 (7%) had acquired immunodeficiency syndrome. Controllers had higher CD4+ and CD8+ cell activation levels (P < .001 for both) than HIV-negative subjects and higher CD8+ cell activation levels than the antiretroviral therapy suppressed (P = .048). In controllers, higher CD4+ and CD8+ T cell activation was associated with lower CD4+ cell counts (P = .009 and P = .047). Controllers had higher LPS levels than HIV-negative subjects (P < .001), and in controllers higher LPS level was associated with higher CD8+ T cell activation (P = .039). Conclusions. HIV controllers have abnormally high T cell activation levels, which may contribute to progressive CD4+ T cell loss even without measurable viremia.