Protection Versus Pathology in Aviremic and High Viral Load HIV-2 Infection—The Pivotal Role of Immune Activation and T-cell Kinetics

• Published in: The Journal of infectious diseases Vol. 210; no. 5; pp. 752 - 761
• Main Authors: Hegedus, Andrea, Nyamweya, Samuel, Zhang, Yan, Govind, Sheila, Aspinall, Richard, Mashanova, Alla, Jansen, Vincent A. A., Whittle, Hilton, Jaye, Assan, Flanagan, Katie L., Macallan, Derek
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2014
• Subjects: Adult; AIDS; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Gambia; HIV; HIV 1; HIV 2; HIV infections; HIV Infections - immunology; HIV Infections - virology; HIV Long-Term Survivors; HIV-2 - immunology; HIV/AIDS; Human immunodeficiency virus 1; Human immunodeficiency virus 2; Human viral diseases; Humans; Infectious diseases; Lymphocytes; Major and Brief Reports; Male; Medical sciences; Memory; Microbiology; Middle Aged; Miscellaneous; T lymphocytes; T-Lymphocytes - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Viremia; Virology; Young Adult; Gambia; Immunopathology; Retroviridae; AIDS; Immune deficiency; Lentivirus; HIV-2 virus; Virus; Infection; Viral disease; T-Lymphocyte; Human immunodeficiency virus; Kinetics; Viral load; HIV-1; CD4; HIV pathogenesis; HIV-2; T-cell; immune memory; CD8; immune activation
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiu165

Background. Many human immunodeficiency virus (HIV)-2-infected individuals remain aviremic and behave as long-term non-progressors but some progress to AIDS. We hypothesized that immune activation and T-cell turnover would be critical determinants of non-progressor/progressor status. Methods. We studied 37 subjects in The Gambia, West Africa: 10 HIV-negative controls, 10 HIV-2-infected subjects with low viral loads (HIV-2-LV), 7 HIV-2-infected subjects with high viral loads (HIV-2-HV), and 10 with HIV-1 infection. We measured in vivo T-cell turnover using deuterium-glucose labeling, and correlated results with T-cell phenotype (by flow cytometry) and T-cell receptor excision circle (TREC) abundance. Results. Immune activation (HLA-DR/CD38 coexpression) differed between groups with a significant trend: controls <HIV-2-LV <HIV-1 <HIV-2-HV (P < .01 for all cell types). A similar trend was observed in the pattern of in vivo turnover of memory CD4⁺ and CD8⁺ T-cells and TREC depletion in naive CD4⁺ T-cells, although naive T-cell turnover was relatively unaffected by either infection. T-cell turnover, immune activation, and progressor status were closely associated. Conclusions. HIV-2 non-progressors have low rates of T-cell turnover (both CD4⁺ and CDS⁺) and minimal immune activation; high viral load HIV-2 progressors had high values, similar to or exceeding those in HIV-1 infection.