title: Impact of suppression of viral replication by highly active antiretroviral therapy on immune function and phenotype in chronic HIV-1 infection.
abstract: We compared immune phenotypes, lymphocyte proliferation (LP), and delayed type hypersensitivity (DTH) responses in 28 male antiretroviral treatment-naive and experienced HIV-1-infected patients, matched pair-wise according to age and CD4+ T-lymphocyte count. Median CD4+ T-lymphocyte counts were 441 cells/microL and 483 cells/microL and median CD4+ T-lymphocyte nadirs were 435 cells/microL and 150 cells/microL in both groups, respectively. Absolute numbers of circulating T-lymphocyte subpopulations and proportions of naive and memory T-lymphocytes were comparable in the two groups. Untreated patients had greater proportions of activated CD4+ (p <.05) and CD8+ (p <.01) T-cells expressing human leukocyte antigen (HLA)DR and CD38 and fewer CD8+ cells expressing CD28 (p <.05). DTH and LP responses were comparable in both groups except for HIVp24, LP responses, and mumps DTH responses, which were of greater magnitude in the group treated with highly active antiretroviral therapy (HAART) (p <.05). Thus, HIV-1-infected patients who experienced substantial increases in CD4+ T-lymphocyte counts after suppression of viral replication on HAART had fewer activated lymphocytes and similar immune function when compared with findings in untreated patients with similar CD4+ T-cell counts. HIV replication has minimal real-time effect on CD4+ T-cell function in response to non-HIV antigens but helper T-cell responses to HIV-gag antigen are impaired during ongoing viral replication and may be restored by antiretroviral therapy.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Center for AIDS Research, Case Western Reserve University and University Hospitals of Cleveland, Ohio 44106, USA.
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Lange
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Juan Sierra
authors.initials: JS
authors.lastname: Madero
authors.forename: Kathy
authors.initials: K
authors.lastname: Medvik
authors.forename: Robert
authors.initials: R
authors.lastname: Asaad
authors.forename: Christina
authors.initials: C
authors.lastname: Pacheko
authors.forename: Claudia
authors.initials: C
authors.lastname: Carranza
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D023241:Antiretroviral Therapy, Highly Active; D018106:CD28 Antigens / Q000032:analysis; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1