Early correction of cell cycle perturbations predicts the immunological response to therapy in HIV-infected patients

Objective: To determine whether changes in the indices of HIV-associated cell cycle dysregulation (i.e., increased expression of cyclin B1 and abnormal nucleolar structure) may predict the level of immunological reconstitution in HIV-infected patients treated with highly active antiretroviral therapy (HAART). Methods: Cross-sectional and longitudinal analysis of viral load, CD4 T cell counts, cyclin B1 expression, and AgNOR number and area of distribution in 30 HIV-infected patients who were studied before and up to 6 months after initiation of HAART. Results: In HIV-infected individuals, the level of cell cycle dysregulation correlated with the type of response to HAART. While low levels of dysregulation were present in patients with complete (both virological and immunological) response to HAART, high levels were present in HAART-treated patients with limited CD4 T cell increases despite persistent viral suppression (immunological non-responders). Importantly, the level of correction of cell cycle dysregulation after 60 days of therapy predicted the level of immune reconstitution after 6 months. Conclusion: These observations suggest that correction of cell cycle dysregulation predicts a good immunological response to HAARTand that sequential analysis of cell cycle dysregulation might help to identify patients that could benefit from alternative, immune-based interventions in addition to standard HAART.