Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function
- 1 September 2001
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in AIDS
- Vol. 15 (14), 1749-1756
- https://doi.org/10.1097/00002030-200109280-00002
Abstract
To characterize immune phenotype and thymic function in HIV-1-infected adults with excellent virologic and poor immunologic responses to highly active antiretroviral therapy (HAART). Cross-sectional study of patients with CD4 T cell rises of > or = 200 x 10(6) cells/l (CD4 responders; n = 10) or < 100 x 10(6) cells/l (poor responders; n = 12) in the first year of therapy. Poor responders were older than CD4 responders (46 versus 38 years; P < 0.01) and, before HAART, had higher CD4 cell counts (170 versus 35 x 106 cells/l; P = 0.11) and CD8 cell counts (780 versus 536 x 10(6) cells/l; P = 0.02). After a median of 160 weeks of therapy, CD4 responders had more circulating naive phenotype (CD45+CD62L+) CD4 cells (227 versus 44 x 10(6) cells/l; P = 0.001) and naive phenotype CD8 cells (487 versus 174 x 10(6) cells/l; P = 0.004) than did poor responders (after 130 weeks). Computed tomographic scans showed minimal thymic tissue in 11/12 poor responders and abundant tissue in 7/10 responders (P = 0.006). Poor responders had fewer CD4 cells containing T cell receptor excision circles (TREC) compared with CD4 responders (2.12 versus 27.5 x 10(6) cells/l; P = 0.004) and had shorter telomeres in CD4 cells (3.8 versus 5.3 kb; P = 0.05). Metabolic labeling studies with deuterated glucose indicated that the lower frequency of TREC-containing lymphocytes in poor responders was not caused by accelerated proliferation kinetics. Poor CD4 T cell increases observed in some patients with good virologic response to HAART may be caused by failure of thymic T cell production.Keywords
This publication has 44 references indexed in Scilit:
- Changing Spectrum of Mortality Due to Human Immunodeficiency Virus: Analysis of 260 Deaths during 1995-1999Clinical Infectious Diseases, 2001
- Immune Reconstitution in the First Year of Potent Antiretroviral Therapy and Its Relationship to Virologic ResponseThe Journal of Infectious Diseases, 2000
- Immune Reconstitution after 2 Years of Successful Potent Antiretroviral Therapy in Previously Untreated Human Immunodeficiency Virus Type 1–Infected AdultsThe Journal of Infectious Diseases, 1999
- Combination Antiretroviral Therapy and Recent Declines in AIDS Incidence and MortalityThe Journal of Infectious Diseases, 1999
- Immunologic Responses Associated with 12 Weeks of Combination Antiretroviral Therapy Consisting of Zidovudine, Lamivudine, and Ritonavir: Results of AIDS Clinical Trials Group Protocol 315The Journal of Infectious Diseases, 1998
- Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus InfectionNew England Journal of Medicine, 1998
- Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: A composite of redistribution and proliferationNature Medicine, 1998
- Treatment with Indinavir, Zidovudine, and Lamivudine in Adults with Human Immunodeficiency Virus Infection and Prior Antiretroviral TherapyNew England Journal of Medicine, 1997
- A Controlled Trial of Two Nucleoside Analogues plus Indinavir in Persons with Human Immunodeficiency Virus Infection and CD4 Cell Counts of 200 per Cubic Millimeter or LessNew England Journal of Medicine, 1997
- Positive Effects of Combined Antiretroviral Therapy on CD4 + T Cell Homeostasis and Function in Advanced HIV DiseaseScience, 1997