JAC Advance Access originally published online on July 16, 2009
Journal of Antimicrobial Chemotherapy 2009 64(3):579-588; doi:10.1093/jac/dkp248
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Original research |
Premature immunosenescence in HIV-infected patients on highly active antiretroviral therapy with low-level CD4 T cell repopulation
1 Laboratory of Inmunovirology, Service of Infectious Diseases, University Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain 2 Laboratory of Molecular Virology, Service of Infectious Diseases, University Hospital Virgen del Rocío, Sevilla, Spain 3 Laboratory of Molecular Immunobiology, Gregorio Marañon University General Hospital, Madrid, Spain 4 Unit of Investigation, Instituto de Salud Carlos III, Madrid, Spain
Received 8 January 2009; returned 5 April 2009; revised 2 June 2009; accepted 21 June 2009
* Corresponding author. Laboratorio de Inmunovirología, Servicio de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocío, Manuel Siurot s/n, 41013 Seville, Spain. Tel: +34-955-012-391; Fax: +34-955-013-292; E-mail: mleal{at}telefonica.net
Objectives: To analyse the role of thymic function and its association with cellular immunosenescence markers in patients with low-level CD4 T cell repopulation, despite complete HIV RNA replication control on highly active antiretroviral therapy (HAART).
Methods: Cellular immunosenescence markers comparing patients with CD4 T cell counts 
250 cells/mm3 for 
48 weeks (n = 11) and patients with a CD4 T cell count 500 cells/mm3 (n = 11) were investigated. Both groups were also compared with 11 healthy volunteers of similar age. Naive CD4 T cell counts, β- and 
-T cell rearrangement excision circles, recent thymic emigrants, replicative senescence marker, cell activation, and rate of apoptosis were analysed. The Mann–Whitney U-test was used to compare parameters between both low-level and high-level CD4 T cell repopulation groups, and healthy volunteers.
Results: Our results showed a lower thymic activity in patients with low-level CD4 T cell repopulation, leading to a decline in CD4 T cell production. On the other hand, a higher activation along with a higher replicative senescence of CD4 T cells contributed to a higher rate of apoptotic CD4 T cells in this group of patients.
Conclusions: We propose a model with several different related mechanisms involved in premature immune senescence in HIV-infected patients with low-level CD4 repopulation on HAART. The understanding of such different mechanisms could help find effective strategies to prevent immune decay.
Keywords: CD4 T cells , HIV , activation , apoptosis , thymic function , senescence , HAART
These authors contributed equally to this work.