[15] IMMUNOLOGICAL IMPROVEMENT FOLLOWING HAART COINCIDES WITH RESTORED THYMIC FUNCTION

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] IMMUNOLOGICAL IMPROVEMENT FOLLOWING HAART COINCIDES WITH RESTORED THYMIC FUNCTION

[AUTHOR(S):] R Cheynier¹, R Bordi², ML Dion², R Woods³, J Montaner³, F Harris⁴, M Lederman⁵ and RP Sékaly²
¹Unité des Virus Lents, Institut Pasteur, Paris, France; ²Centre de recherche du CHUM, Montréal, QC, Canada; ³British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital, Vancouver, BC, Canada; ⁴Boehringer Ingelheim, Burlington, ON, Canada; and ⁵ Case Western Reserve University Cleveland, OH, USA

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 15
Antiviral Therapy 2003; 8(Suppl. 1):S189

[ABSTRACT:] Involvement of thymic function in the natural history of HIV pathogenesis and its importance in immune reconstitution following initiation of HAART is yet to be confirmed. We have developed a novel assay that relies on measuring T cell receptor excision circles (TRECS) generated early (βTRECs) and late (sjTREC) during thymopoiesis. The sj/βTREC ratio, measured in peripheral blood provides a quantitative assessment of intrathymic precursor T cell proliferation. It follows the sjTREC frequency, declines with age and is independent from any peripheral proliferative event. The sj/βTREC ratio thus represents a good surrogate marker for thymic output even in the presence of important peripheral homeostatic perturbations. The sjTREC and βTRECs frequencies were assessed by real time quantitative PCR in a group of 44 chronically infected patients with variable viral loads and CD4 counts. In each case, the sj/βTREC ratio was calculated and analyzed in regards to the clinical status of the patient. Four major observations can be made from our results. 1) Thymopoiesis is severely impaired during chronic HIV infection as a consequence of limited intrathymic T cell proliferation demonstrated by the increased βTRECs frequencies. 2) This defect is partly restored under efficient antiretroviral therapy. However, thymic response to treatment, as demonstrated by an increase of the sj/βTREC ratio, is significantly delayed in patients treated during chronic infection, as compared to patients treated during primary infection. 3) Poor responders to therapy (i.e. patients who do not restore CD4 counts despite viral suppression) are never able to reconstitute the sj/βTREC ratio. 4) In patients with virologic failure viral load rebound is concordant with a drop of thymic function and precedes CD4 counts decline. The positive correlation between CD4 counts and intrathymic proliferation in HAART treated patients suggests the important role of thymic function in immune reconstitution following HAART.

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