title: Short-term antiretroviral therapy fails to reduce the expanded activated CCR5-expressing CD4+ T lymphocyte population or to restore the depleted naive population in chronically HIV-infected individuals with active pulmonary tuberculosis.
abstract: The effective role of antiretroviral (ARV) therapy in the regulation of CD4 T cell subset distribution, coreceptor expression, and activation status in individuals with chronic HIV also presenting with active pulmonary TB is not clearly understood. A cross-sectional analysis was performed on a total of 137 South African individuals. CCR5, CXCR4, and CD38 expression of CD4 T cell subsets in HIV-infected individuals with and without active pulmonary tuberculosis (TB) disease, pre- and post-ARV therapy, were determined by flow cytometry. In treatment-naive patients, CD4 T cells showed elevated surface expression of CCR5 and CD38 in TB/HIV coinfection as compared to HIV infection alone despite the overall percentage of CD4 T cells expressing CCR5 being reduced. Total CD38+ CD4 T cells were not significantly increased in either group; however, mean CD38 fluorescence was significantly higher in the context of TB infection. HIV/TB-coinfected individuals also displayed an increased percentage of activated (CD38+) CCR5+ CD4 T cells as compared to HIV patients alone. The naive CD4 T cell subset was depleted similarly in both HIV and HIV/TB groups. Only the HIV treatment group and not the TB-coinfected treatment group showed significantly decreased activated CCR5+ CD4 T cells, an increased percentage of naive T cells, and a decreased percentage of antigen-experienced T cells. This study highlighted an association of TB disease with immune activation, particularly of the CCR5+ CD4 T cell subset in HIV infection and the differential impact of ARV treatment. Further studies are needed to understand how TB coinfection confounds normal responses to ARV.
authors.affiliation: Medical Virology Division, Department of Pathology, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Kabue
authors.forename: Dalene
authors.initials: D
authors.lastname: de Swardt
authors.forename: Corena
authors.initials: C
authors.lastname: de Beer
authors.forename: Richard H
authors.initials: RH
authors.lastname: Glashoff
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000187:drug effects / Q000276:immunology; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D060085:Coinfection / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000187:drug effects / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000276:immunology; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; C527276:CXCR4 protein, human; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D051997:ADP-ribosyl Cyclase 1