Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV-1 infection.
OBJECTIVE
We aimed to provide evidence of thymic reconstitution after highly active antiretroviral therapy (HAART) in HIV-1 infected patients and to correlate this with the restoration of peripheral naïve T cells.


METHODS
Positron emission tomography (PET) enables definitive evidence of thymic activity, indicating functional potential. In this case study, a single patient who initiated HAART demonstrated reconstitution of the naïve T-cell pool and underwent thymic PET scans at baseline and 2 and 6 months following initiation of therapy. Two patients who failed to demonstrate such reconstitution acted as controls. These patients (mean age 27 years) had chronic HIV infection with low CD4 T-cell counts (mean 82, range 9-160 cells/microL blood). Increased function of the thymus visualized by PET was correlated with phenotypic changes in CD4 and CD8 T cells in the periphery measured by flow cytometry, and with numbers of recent thymic emigrants measured by quantification of the numbers of T-cell receptor excision circles (TRECs) in peripheral cells.


RESULTS
In one patient, clear correlations could be drawn between visible activity within the thymus, as measured by increased [F18]fluorodeoxyglucose (FDG) uptake, and regeneration of naïve CD4 (CD45RA/CD62L) T cells, increased numbers of CD4 T cells, controlled viraemia and increased numbers of recent thymic emigrants. A second patient displayed no increase in peripheral CD4 count and no increase in thymic activity. The third patient elected to stop therapy following the 2-month time point.


CONCLUSIONS
The use of PET suggests that thymic activity may increase after HAART, indicating that the thymus has the potential to be functional even in HIV-1 infected persons with low CD4 T-cell counts.
Hardy
G
G
Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, London, UK. g.hardy@medsch.ucl.ac.uk
Worrell
S
S
Hayes
P
P
Barnett
C M
CM
Glass
D
D
Pido-Lopez
J
J
Imami
N
N
Aspinall
R
R
Dutton
J
J
Gazzard
B
B
Peters
A M
AM
Gotch
F M
FM
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015658:HIV Infections / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D010349:Patient Compliance; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000000981:diagnostic imaging / Q000276:immunology*; D014055:Tomography, Emission-Computed / Q000379:methods; D016896:Treatment Outcome; D019562:Viral Load