title: T-cell receptor excisional circles, telomere length, proliferation and apoptosis in peripheral blood mononuclear cells of human immunodeficiency virus-infected individuals after 18 months of treatment induced viral suppression.
abstract: This study evaluated the effect of highly active antiretroviral therapy (HAART)-induced viral suppression on T-cell receptor excisional circles (TRECs), telomere length, proliferative responses and spontaneous as well as phytohaemagglutinin (PHA)-stimulated lymphocyte apoptosis in 27 human immunodeficiency virus (HIV)-infected individuals followed for 18 months during HAART. Our results show that HAART significantly increased the level of TRECs in CD4+ cells (P = 0.003) after 18 months of almost continuously suppressed HIV-RNA levels. Lymphocyte proliferative responses and apoptosis levels in patients were significantly lower and significantly higher, respectively, compared with healthy controls. The proliferative response and apoptosis levels did not change during follow up. Changes in telomere length were observed in CD4+ and in CD8+ T cells. The study demonstrated that HAART induces normal TREC levels in the CD4+ T-cell pool. However, the other perturbed functions in T cells indicate that immune reconstitution is incomplete and may need longer viral suppression.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. hssa@novonordisk.com
authors.forename: H
authors.initials: H
authors.lastname: Aladdin
authors.forename: T
authors.initials: T
authors.lastname: Katzenstein
authors.forename: A-M
authors.initials: AM
authors.lastname: Dreves
authors.forename: L
authors.initials: L
authors.lastname: Ryder
authors.forename: J
authors.initials: J
authors.lastname: Gerstoft
authors.forename: P
authors.initials: P
authors.lastname: Skinhøj
authors.forename: B K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: H
authors.initials: H
authors.lastname: Ullum
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000187:drug effects; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry; D016615:Telomere / Q000648:ultrastructure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA