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Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV‐1 infection
Author(s) -
Hardy G,
Worrell S,
Hayes P,
Barnett CM,
Glass D,
PidoLopez J,
Imami N,
Aspinall R,
Dutton J,
Gazzard B,
Peters AM,
Gotch FM
Publication year - 2004
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2004.00187.x
Subject(s) - medicine , cd8 , flow cytometry , antiretroviral therapy , fluorodeoxyglucose , immunology , human immunodeficiency virus (hiv) , t cell , positron emission tomography , viral load , immune system , nuclear medicine
Objectives 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 initiatiated 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/μL 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.