T-Cell Activation Independently Associates With Immune Senescence in HIV-Infected Recipients of Long-term Antiretroviral Treatment

• Published in: The Journal of infectious diseases Vol. 214; no. 2; pp. 216 - 225
• Main Authors: Jimenez, Viviana Cobos, Wit, Ferdinand W. N. M., Joerink, Maaike, Maurer, Irma, Harskamp, Agnes M., Schouten, Judith, Prins, Maria, van Leeuwen, Ester M. M., Booiman, Thijs, Deeks, Steven G., Reiss, Peter, Kootstra, Neeltje A.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.07.2016
• Subjects: Aged; Aging; Anti-Retroviral Agents - therapeutic use; Cohort Studies; Cytomegalovirus; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunophenotyping; Lipopolysaccharide Receptors - blood; Lymphocyte Activation; Major and Brief Reports; Male; Middle Aged; Programmed Cell Death 1 Receptor - analysis; T-Lymphocyte Subsets - chemistry; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology; Telomere - metabolism; Thymus Gland - immunology; senescence; thymic output; ART; HIV; immune activation; telomeres
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiw146

Background. Aging-associated noncommunicable comorbidities are more prevalent among human immunodeficiency virus type 1 (HIV)-infected individuals than among HIV-uninfected individuals. Residual HIV-related chronic immune activation and senescence may increase the risk of developing comorbidities. Methods. Immune phenotyping, thymic output, and telomere length were assessed in 94 HIV-infected individuals who were aged >45 years and receiving antiretroviral therapy (ART; cases) and 95 age-matched uninfected controls. Results. Cases had lower CD4⁺ T-cell counts, higher CD8⁺ T-cell counts, and increased levels of immune activation (ie, increased soluble CD 14 [sCD14] level and increased percentages of CD38⁺ HLA-DR⁺ cells among both CD4⁺ and CD8⁺ T cells), regulatory T cells, and percentage of programmed cell death 1 (PD-l)-expressing cells among CD4⁺ T cells. Immune senescence levels (ie, percentages of CD27⁻ CD28⁻ cells or CD57⁺ cells) were comparable between cases and controls. Peripheral blood mononuclear cells from cases had shorter telomeres but increased single-joint T-cell receptor excision circle content and CD31⁺ naive CD4⁺ T cells. Although cytomegalovirus (CMV) antibody titers were higher in cases, CMV-specific T-cell responses were comparable between cases and controls. T-cell senescence in cases was independently associated with T-cell activation but not with CMV-specific immune responses. Conclusions. Despite long-term receipt of ART, HIV-infected adults had higher levels of immune activation, regulatory T cells, and PD-1-expressing CD4⁺ cells and shorter telomeres. The increased soluble CD14 levels and percentage of CD38⁺ HLA-DR⁺ cells among CD4⁺ T cells correlated with shorter telomeres and increased regulatory T-cell levels. This suggests that HIV influences immune function irreversibly, with several pathways that are persistently abnormal during effective ART. Therapies aimed at improving immune health during ART are needed.