Immunological and virological failure after antiretroviral therapy is associated with enhanced peripheral and thymic pathogenicity.
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.
Solomon
Ajantha
A
Department of Microbiology and Immunology, University of Melbourne, and Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Australia.
Cameron
Paul U
PU
Bailey
Michael
M
Dunne
Amanda L
AL
Crowe
Suzanne M
SM
Hoy
Jenny F
JF
Lewin
Sharon R
SR
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
D019380:Anti-HIV Agents