학술논문

Subclinical Cytomegalovirus DNA Is Associated with CD4 T Cell Activation and Impaired CD8 T Cell CD107a Expression in People Living with HIV despite Early Antiretroviral Therapy.
Document Type
article
Source
Journal of Virology. 93(13)
Subject
Medical Microbiology
Biomedical and Clinical Sciences
Immunology
HIV/AIDS
Clinical Research
Infectious Diseases
Aetiology
2.1 Biological and endogenous factors
Infection
Good Health and Well Being
Adult
Anti-HIV Agents
Anti-Retroviral Agents
CD4-CD8 Ratio
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Coinfection
Cytomegalovirus
DNA Viruses
HIV Infections
HIV-1
Herpesvirus 4
Human
Humans
Lymphocyte Activation
Male
Programmed Cell Death 1 Receptor
Sexual and Gender Minorities
Virus Replication
Virus Shedding
CMV
HIV
T cells
immune dysfunction
Biological Sciences
Agricultural and Veterinary Sciences
Medical and Health Sciences
Virology
Agricultural
veterinary and food sciences
Biological sciences
Biomedical and clinical sciences
Language
Abstract
Most people living with HIV (PLWH) are coinfected with cytomegalovirus (CMV). Subclinical CMV replication is associated with immune dysfunction and with increased HIV DNA in antiretroviral therapy (ART)-naive and -suppressed PLWH. To identify immunological mechanisms by which CMV could favor HIV persistence, we analyzed 181 peripheral blood mononuclear cell (PBMC) samples from 64 PLWH starting ART during early HIV infection with subsequent virologic suppression up to 58 months. In each sample, we measured levels of CMV and Epstein-Barr virus (EBV) DNA by droplet digital PCR (ddPCR). We also measured expression of immunological markers for activation (HLA-DR+ CD38+), cycling (Ki-67+), degranulation (CD107a+), and the immune checkpoint protein PD-1 on CD4+ and CD8+ T cell memory subsets. Significant differences in percentages of lymphocyte markers by CMV/EBV shedding were identified using generalized linear mixed-effects models. Overall, CMV DNA was detected at 60/181 time points. At the time of ART initiation, the presence of detectable CMV DNA was associated with increased CD4+ T cell activation and CD107a expression and with increased CD8+ T cellular cycling and reduced CD107a expression on CD8+ T cells. While some effects disappeared during ART, greater CD4+ T cell activation and reduced CD107a expression on CD8+ T cells persisted when CMV was present (P