Immune modulators and treatment interruption

This article reviews the relevance of sudden immune activation in HIV pathogenesis and summarizes the strategies that could prevent the high peaks of viral replication after antiretroviral therapy interruption.

Systemic immune activation could have both beneficial and harmful effects in chronic infection. Recent findings suggest that in addition to viral replication other factors could drive immune activation. The changes in natural regulatory T cell number or function and microbial translocation have been hypothesized as potential causes. Immune activation after antiretroviral therapy interruption could play a critical role in the increase in the rates of AIDS-defining and non-AIDS-defining malignancies or cardiovascular events between patients on a CD4 T-cell-guided intermittent antiretroviral therapy strategy in the SMART study.

The use of a cytostatic drug would help T lymphocytes to remain quiescent, becoming refractory to productive HIV-1-infection and thus avoiding high peaks of viral replication after antiretroviral interruption without blunting HIV-1 specific immune responses. This has been the rationale for the use of immunomodulators (such as corticosteroids, hydroxyurea, mycophenolate mofetil, thalidomide, and cyclosporin A) as adjuvant to antiretroviral therapy in structured treatment interruption strategies.