Initiation of c-ART in HIV-1 infected patients is associated with a decrease of the metabolic activity of the thymus evaluated using FDG-PET/computed tomography.
BACKGROUND
The role of the thymus in the depletion or restoration of T-cell pool in HIV infection is still debatable. Studies are hampered by the lack of valuable tools to investigate thymic activity.


METHODS
We have evaluated thymic activity using (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography and molecular and phenotypic analyses of thymic precursors. Longitudinal analyses were performed in HIV-infected patients either treatment naive with indication to initiate combination antiretroviral therapy (c-ART) (n = 11) or stable under c-ART (n = 9).


RESULTS
Thymic standardized uptake value was significantly lower in c-ART-treated patients as compared with historical age-matched HIV-negative controls. In c-ART-naive patients, baseline thymic standardized uptake value correlated with T-cell repector excision circle levels and naive CD4+ T cells. These patients exhibited a high metabolic lymph node activity positively correlated to the percentage of activated HLA-DR+CD38+ T cells. Basal metabolic thymic activity predicts the gain in CD4+ T cells after c-ART initiation. A decrease of thymic activity, which paralleled circulating plasma IL-7 levels, was noted after c-ART initiation.


CONCLUSIONS
A metabolic thymic activity is detectable in c-ART naive and correlates with indirect phenotypic and molecular markers of thymic output. This activity may participate to the pool of peripheral naive CD4+ T cells and predicts the magnitude of T-cell reconstitution under treatment.
INSERM, Unite U955, Creteil, France. jean-daniel.lelievre@hmn.aphp.fr
Jean-Daniel
JD
Lelièvre
Giovanna
G
Melica
Emmanuel
E
Itti
Christine
C
Lacabaratz
Sandra
S
Rozlan
Aurélie
A
Wiedemann
Rémi
R
Cheynier
Michel
M
Meignan
Rodolphe
R
Thiebaut
Yves
Y
Levy
D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
D044966:Anti-Retroviral Agents