Changes in thymic function in HIV-positive patients treated with highly active antiretroviral therapy and interleukin-2

Despite its potent antiviral activity, highly active antiretroviral therapy (HAART) only exerts a marginal effect on CD4(+) T-cell regeneration in HIV -infected subjects. Combination therapies aimed at boosting T-cell activity and maturation may provide an important contribution to the restoration of immune function. Here, we report the results obtained by a two-year follow -up of a cohort of HIV-infected patients treated with a combination of HAAR T and interleukin-2 (IL-2). In these patients, in addition to a series of q uantitative virological and immunological parameters, we investigated T-cel l regeneration by an immunophenotypic assay monitoring CD4(+) naive T cells , and by analysis of thymic function, through the quantification of the exc ision DNA products of T-cell receptor rearrangement (TRECs) in lymphocytes. Compared with HAART alone, we found that the IL-2 combination therapy was equally effective in reducing the levels of viremia and marginally more eff ective in decreasing proviral DNA load. Strikingly, the IL-2 combination pr oduced a marked increase in the number of CD4(+) T cells bearing a naive ph enotype (CD45RA(+), CD62L(+)), which was apparent for over 96 weeks after t herapy. To assess whether these cells were the product of improved T-cell g eneration, we exploited a competitive quantitative molecular assay to quant ify TRECs in peripheral blood lymphocytes. Surprisingly, we found that the levels of these molecules were unchanged in these patients. These findings indicate that improved thymic function does not account for the early rise of CD4 naive cells in HIV-positive patients treated with IL-2, and suggest that alternative mechanisms of T-cell maturation and differentiation are re sponsible for this event.