Longitudinal changes in HIV-specific IFN-? secretion in subjects who received Remune™ vaccination prior to treatment interruption

Abstract

BACKGROUND:Despite the benefits of highly active antitretroviral therapy (HAART) for suppressing viral replication in HIV infection, virus persists and rebounds during treatment interruption (TI). This study explored whether HAART intensification with Remune™ vaccination before TI can boost HIV-1-specific immunity, leading to improved control of viremia off HAART.METHODS:Ten chronically HIV-infected adults were enrolled in this proof of concept study. After a 6-month HAART intensification phase with didanosine, hydroxyurea, granulocyte-macrophage colony-stimulating factor, (GM-CSF), and a first dose of Remune™ (HIV-1 Immunogen), HAART was discontinued. Patients continued to receive Remune™ every 3 months until the end of study. HAART was restarted if viral load did not fall below 50,000 copies/ml of plasma within 3 months or if CD4+ counts decreased to <200 cells/mm3. HIV-specific immunity was monitored with the interferon-? (IFN-?) ELISPOT assay.RESULTS:All subjects experienced viral rebound during TIs. Although the magnitude and breadth of HIV-specific responses to HLA-restricted optimal peptide panels and Gag p55 peptide pools increased and viral load decreased by 0.44 log10 units from TI#1 to TI#2, no significant correlations between these parameters were observed. The patients spent 50.4% of their 36 months follow up off HAART.CONCLUSION:Stopping HAART in this vaccinated population induced immune responses that persisted after therapy was restarted. Induction of HIV-specific immunity beyond IFN-? secretion may be contributing to better control of viremia during subsequent TIs allowing for long periods off HAART.