Interestingly, both sjTREC quantification (sjTREC/mL) and intrathymic precursor T-cell proliferation (sj/bTREC ratio) were affected very early on after initiation of therapy ( Figures 2B and  3B ). While sjTREC frequency and concentration in peripheral blood can be affected by modifications of parameters that impact on peripheral T-cell homeostasis (cycling, survival/apoptosis, homing), the sj/bTREC ratio is a marker of the intrathymic proliferation history of RTEs. Indeed, this parameter is generated by cell proliferation that occurs between TCRb chain rearrangement and the excision of TCRd locus. Further cell cycling after TCRa chain rearrangement does not modify the sj/bTREC ratio as both type of TRECs are similarly diluted upon cell proliferation. Accordingly, while exported to the periphery, the sj/bTREC ratio of mature T-cells cannot be modified. Therefore, while the observed decrease in sjTREC concentration (figure 2) can be a consequence of modifications of circulating T-cell homeostasis, the decline of the sj/bTREC ratio observed during the first months of IFNa therapy (figure 3) defines changes in thymocyte proliferation, thus in thymic output [28] . Acutely infected patients demonstrated a higher sj/bTREC ratio at baseline than patients in the chronic phase. However, this group was younger (Median = 31.5 (26-47)) versus Median = 53.5 (37-61)) than the chronic group (p,0.01; data not shown) and demonstrated normal sj/bTREC ratio for their age. Similar evolution of thymic function and circulating T-cell subsets were observed in both groups of HCV-infected patients, irrespective of the development stage of HCV pathology. The lack of effect of IFNa therapy in HIV/HCV co-infected patients might be due to the fact that, as expected for chronically HIV-infected individuals, these patients already had a low thymic function at study entry. The impairment of thymopoiesis in HCV-infected patients under IFNa therapy is reminiscent of that observed during the acute phase of HIV-1 infection [23] which suggested that long term production of IFNa, as part of the anti-HIV innate immune response, may play a role in the observed thymic defect. The correlation between decline in IL-7 plasma levels under IFNa therapy and both thymic dysfunction and reduced T-cell counts, in particular in the naïve and RTE compartments ( Figures 5A and  5B) , confirms this hypothesis. Finally, in a recent study, we showed that IFNa treatment leads to decreased sjTREC frequency as well as reduced naïve T-cell and RTE counts in SIV-infected rhesus macaques [30] . Such an effect was accompanied by a 30-40% decrease in IL-7 plasma levels in these animals and could be counteracted by injection of recombinant simian IL-7 [30] . One could expect that such an effect of type I IFNs is not restricted to HIV-infection as many viral infections induce IFNa responses and cause transient lymphocytopenia in the infected hosts [3, 4, 5, 6] .