Distinct mechanisms of T cell reconstitution can be identified by estimating thymic volume in adult HIV-1 disease.
BACKGROUND
We have attempted to identify factors associated with T cell reconstitution in response to highly active antiretroviral therapy.


METHODS
In a prospective, multicenter cohort study, we compared clinical, immune, and viral responses to an initial antiretroviral regimen in older (>or=45 years old) versus younger (18-30 years old) human immunodeficiency virus type 1-infected subjects. Multivariable linear-regression models identified independent factors associated with changes in T cell counts.


RESULTS
Older subjects had smaller increases in naive T cells but greater T cell receptor-excision circle DNA content after 48 weeks, despite similar virologic responses and comparable reductions in immune activation. Changes in T cell counts were associated with plasma interleukin (IL)-7 levels in subjects with low thymic scores, whereas first-phase T cell increases (perhaps mediated by redistribution to the circulation of tissue-associated lymphocytes) were associated with reductions in immune activation in subjects with high thymic scores. Reductions in immune activation were associated with reductions in spontaneous lymphocyte apoptosis.


CONCLUSIONS
Distinct processes may underlie T cell restoration, according to estimated thymic volumes. IL-7-mediated peripheral expansion may drive T cell restoration in persons with low thymic volume, whereas therapy-associated reversal of immune reactivation may drive T cell losses and their restoration in persons with larger thymic volume.
Kalayjian
Robert C
RC
Division of Infectious Diseases, MetroHealth Medical Center and Case Western Reserve University, Cleveland, Ohio 44109-1998, USA. rkalayjian@metrohealth.org
Spritzler
John
J
Pu
Minya
M
Landay
Alan
A
Pollard
Richard B
RB
Stocker
Vicki
V
Harthi
Lena-Al
LA
Gross
Barry H
BH
Francis
Isaac R
IR
Fiscus
Susan A
SA
Tebas
Pablo
P
Bosch
Ronald J
RJ
Valcour
Victor
V
Lederman
Michael M
MM
D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D018655:Lymphocyte Count; D008875:Middle Aged; D009929:Organ Size; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000473:pathology*; D016896:Treatment Outcome; D014481:United States
D044966:Anti-Retroviral Agents; D015851:Interleukin-7