Immune recovery in HIV disease: Role of the thymus and T cell expansion in immune reconstitution strategies

While the progressive depletion of CD4⁺ T cells is the hallmark of the impact of HIV on the immune system, considerable data also point to the loss of T cell function. The question is: Can the immune system recover from this insult and what are the therapeutic strategies available to us to mediate this immune recovery? This review will focus on our current knowledge of immune recovery following treatment with highly active antiretroviral therapy (HAART). Enhancement of thymic function in generating de novo T cell synthesis post-HAART has also emerged as a viable immune recovery strategy. Advances in molecular (T cell receptor excision circle assay) and conventional (computed tomography scans of the thymus) approaches to evaluate the role of the thymus in immune recovery as well as potential agents that might enhance thymic output (interleukin-7, IL-7) will contribute greatly to the assessment of the success of these approaches as immune recovery strategies. In this review, we will integrate this new information in the context of the current strategies for HIV therapy leading to long-term immune reconstitution.