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

Abstract

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. MethodsPositron 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/mL 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. ResultsIn 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. ConclusionsThe 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.

Thymopoietic and Bone Marrow Response to Murine Pneumocystis Pneumonia

“…Clinical investigations have shown that the thymic output of naïve CD4 ϩ T cells is activated in HIV-infected patients following highly active antiretroviral therapy (HAART) treatment (11,38). This thymic activation is correlated with the increase in the number of naïve CD4 ϩ T cells and restoration of total CD4 ϩ T cell counts in the peripheral circulation (10,16). Accumulated evidence suggests that the thymic output of naïve CD4 ϩ T cells may play an important role in maintaining or restoring immune function in immunocompromised hosts.…”

PET/CT in the Evaluation of Lymphoma in Patients With HIV-1 With Suppressed Viral Loads

“…PET studies have suggested 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. 7 This cause of thymic uptake is reminiscent of the well-recognized phenomenon seen particularly in young lymphoma patients, namely "rebound" thymic activity, as a hyperplastic reaction to chemotherapy. 8 Although no increased thymic activity was noted in our group, the finding may present a pitfall in scan interpretation and is therefore a point noted here to prevent other potential misinterpretations of scan findings in the future.…”

PET/CT scanning with a high HIV/AIDS prevalence

“…HAART may also induce what appears to be a thymic reactivation in adults [26]. This must also be interpreted in the light of evidence that thymic uptake is often also seen well into adulthood on PET in HIV negative patients [27].…”