Restoration of the immune system with anti-retroviral therapy

Clinical benefits of highly active anti-retroviral treatments (HAART) are i ncreasingly evidenced by resolving opportunistic infections and malignancie s, as well as declining hospitalization and mortality rates [1]. This sugge sts that potent and sustained suppression of viral replication, at least to some extent, is associated with reconstitution of the immune system even i n adult patients treated at advanced stages of the disease. Increased susce ptibility to opportunistic infections and tumors mainly results from the lo ss of memory CD4+ T cell reactivity against recall antigens which is an ear ly event in HIV disease progression. Primary responses of naive CD4+ T cell s against new pathogens are suppressed even earlier in the course of HIV di sease, and the progressive depletion in naive CD4+ T cells reflects profoun d alterations in T cell regeneration capacities. Previous studies revealed that monotherapy with ritonavir, a protease inhibitor, resulted in a slight improvement in memory CD4+ T cell responses to recall Ags only when detect able prior to onset of therapy, suggesting that the loss of CD4+ T cell rea ctivity might be irreversible at advanced stages of the disease [2]. In con trast our group demonstrated more recently that restoration in CD4+ T cell reactivity to specific antigens was feasible when HAART was administered in progressors [3]. Here we address some of the questions raised by immune re storation with HAART when administered at advanced stages of the disease. ( C) 1999 Published by Elsevier Science B.V. All rights reserved.