Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV-1 infection

Gareth Hardy, S. Worrell, P. Hayes, C. M. Barnett, D. Glass, J. Pido-Lopez, N. Imami, R. Aspinall, J. Dutton, B. Gazzard, A. M. Peters, F. M. Gotch

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28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)67-73
Number of pages7
JournalHIV Medicine
Volume5
Issue number2
Early online date10 Mar 2004
DOIs
Publication statusPublished - Mar 2004
Externally publishedYes

Keywords

  • HAART
  • HIV
  • PET
  • Reconstitution
  • Thymus

ASJC Scopus subject areas

  • Health Policy
  • Infectious Diseases
  • Pharmacology (medical)

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    Hardy, G., Worrell, S., Hayes, P., Barnett, C. M., Glass, D., Pido-Lopez, J., ... Gotch, F. M. (2004). Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV-1 infection. HIV Medicine, 5(2), 67-73. https://doi.org/10.1111/j.1468-1293.2004.00187.x