Reduced thymic function predicts low immunologic response to antiretroviral therapy

  • Daniela Ovadia — Agenzia Zoe
  • Medical News
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Key messages

  • Higher levels of thymic function during antiretroviral therapy (ART) were observed in adequate immunological responders (AIR) than poor immunological responders (PIR).
  • Early alterations in immune recoveries were identified as predictors of PIR status after 36 months of therapy.
  • This study may help to identify patients that will benefit from closer follow-up or, in the future, administration of strategies to boost thymic function.

In HIV-positive severely lymphopenic patients, the production of new T cells by thymus is particularly relevant for immune recovery during antiretroviral therapy (ART). In adequate immunological responders (AIR), CD4+ T cell counts attained the range observed in healthy adult individuals (i.e., 500-1500 cells/μL), but these counts remain persistently low in poor immunological responders (PIR), which have higher morbidity and mortality rates.

Authors enrolled 33 patients older than 18 years, chronically infected with HIV-1, with

Two clusters were formed through a posteriori analysis of the CD4+ T cell counts trajectories: the cluster AIR (n=14) included patients with at least one CD4+ T cell count above 500 cells/μL during the first 36 months of ART, and the cluster PIR (n=19) all other patients.

AIR exhibited:

  • Significant increases in thymic volume between baseline during 12 months of ART, while PIR did not (variations of 6.47 ±4.59 cm3 vs. 1.43 ±4.89 cm3, respectively).
  • Significantly higher numbers of signal joint T-cell receptor excision circles (sj-TRECs) /mL of blood and sj/β TREC ratios at 24 months.
  • Higher absolute numbers and percentage of recent thymic emigrants (CD31+CD45RA+CD4+ T cells, a subset of naïve CD4+ T cells with high TREC content) at 12, 24, and 36 months.

Authors focused on parameters at baseline, 2 or 6 months of ART to identify PIR as early as possible. The 4 mathematical multivariate models developed had high sensitivity and specificity and were able to correctly predict PIR/AIR outcome after 36 months of therapy in 77–87% of the cases.

Limitations: results were obtained using a relatively small number of patients from a single hospital.

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