title: Immunological and virological failure after antiretroviral therapy is associated with enhanced peripheral and thymic pathogenicity.
abstract: T cell dynamics and viral genotype were studied in human immunodeficiency virus 1-infected individuals receiving antiretroviral therapy who were viremic and had either increasing (discordant immunological responders) or decreasing (nonresponders) CD4(+) T cell counts. A comparison was made with treated individuals who were not viremic and had increasing CD4(+) T cell counts (complete responders). Nonresponders had higher CD4(+) T cell proliferation (as assessed by Ki67 expression) and immune activation (as assessed by CD38 and human leukocyte antigen-DR expression), together with a reduction in T cell receptor excision circles, compared with discordant immunological responders and complete responders, which suggests that there is enhanced viral pathogenicity in both peripheral T cells and the thymus. Although there was a high prevalence of mutations in the protease and reverse transcriptase genes in discordant immunological responders, these changes were also observed in nonresponders.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, and Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Australia.
authors.forename: Ajantha
authors.initials: A
authors.lastname: Solomon
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Dunne
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Crowe
authors.forename: Jenny F
authors.initials: JF
authors.lastname: Hoy
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013950:Thymus Gland / Q000276:immunology*; D019562:Viral Load; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents