Others and we have documented a strong reduction in the ability of HIV-infected patients to sustain thymic production as a direct consequence of a drop in intrathymic precursor T-cell proliferation [23, 24, 25] . Similar thymic impact was also seen during early SIV-infection in the rhesus macaque model [26] . The capacity of the thymus to produce recent thymic emigrants (RTEs) is, in large part, dependent on thymocyte proliferation [27] . Indeed, extensive thymocyte proliferation occurs between T-cell receptor beta (TCRB) and alpha (TCRA) chain rearrangements. The extent of this proliferation directly correlates with thymic export [28] . The extent of cell proliferation in the thymus can be measured in patients through estimating, in peripheral blood cells, the ratio (sj/bTREC ratio) between the frequency of signal joint T-cell receptor excision circles (sjTREC), produced during the excision of the TCRd locus prior to TCRa chain rearrangement, and that of DbJbTREC T-cell receptor excision circles (TRECs) produced during TCRBD to TCRBJ rearrangement [29] . These by-products of TCR rearrangement processes are generated by the circularization of the chromosomal DNA excised during TCR rearrangements respectively occurring at the DN3 (DbJbTREC) and DP (sjTREC) stages of differentiation. Due to the fact that TRECs do not replicate during mitosis, increased proliferation between DN3 and DP leads to the reduction of DbJbTREC frequency in RTEs as compared to sjTREC frequency and consequently to an increase of the sj/bTREC ratio [23] . The correlation between initial plasma IFNa levels and the speed of thymic dysfunction observed during HIV primary infection suggested that IFNa, produced as part of the innate immune response to infection, participates in the impairment of thymopoiesis. However, no direct evidence of the relationship between IFNa production and thymic dysfunction was provided by these studies. In contrast, Arizcorreta and colleagues showed that IFNa and ribavirin therapy induces a substantial reduction of circulating sjTRECs, in HIV/HCV co-infected patients, accompanied by sustained naïve CD4 + T-cell defect, suggesting thymic dysfunction [10] . Similarly, in the SIV-infected rhesus macaque model, we showed that IFNa therapy induced a strong decrease of circulating RTE numbers as defined either by sjTREC frequency and numbers or by CD31 hi expression on naïve T-cells [30] . Interestingly, in these animals, recombinant interleukin (IL)-7 therapy more than abrogated the deleterious effects of IFNa therapy [30] . IL-7 is a key cytokine implicated at various levels of thymocytes differentiation. It allows cell survival during the rearrangement processes, and is implicated in the extensive thymocyte proliferation, in particular in intermediate single positive (ISP) and early DP cells [31, 32, 33, 34] . This proliferation participates in the development of naïve T-cell diversity [35] . While up regulated by IFNa [36, 37] , the cyclin-dependent kinase inhibitor P27/Kip1 is negatively regulated by IL-7 [38] , allowing ISP and early DP thymocytes to proliferate. Moreover, IFNa also inhibit IL-7 dependent proliferation through down modulation of the common c chain, that participates, together with CD127 to the IL-7 receptor [39] . We here investigated the early impact of IFNa therapy on thymic function and naïve T-cell homeostasis in both HCV-infected and HIV/HCV co-infected patients who started IFNa therapy.