Immune reconstitution under antiretroviral therapy: the new challenge in HIV-1 infection

Although highly active antiretroviral therapy has enabled constant progress in reducing HIV-1 replication, in some patients who are aviremic during treatment, the problem of insufficient immune restoration remains, and this exposes them to the risk of immune deficiency-associated pathologies. Various mechanisms may combine and account for this impaired immunologic response to treatment. A first possible mechanism is immune activation, which may be because of residual HIV production, microbial translocation, co-infections, immunosenescence, or lymphopenia per se. A second mechanism is ongoing HIV replication. Finally, deficient thymus output, sex, and genetic polymorphism influencing apoptosis may impair immune reconstitution. In this review we will discuss the tools at our disposal to identify the various mechanisms at work in a given patient and the specific therapeutic strategies we could propose based on this etiologic diagnosis. (Blood. 2011; 117(21): 5582-5590)