New Data on HIV Reservoirs: Implications for Therapy

Abstract

For years now, AIDS researchers have suspected that most investigations have been focusing on the wrong site, i.e. blood. In fact, it has been well known for over a decade that lymphoid tissue is the key viral replication site from the start of infection, and also a major reservoir and source of virus at all stages of the disease. Lymphoid tissue studies in humans have been impeded by difficulties in obtaining material and, first and foremost, in reiterating sampling. Recent findings in the SIV-infected macaque model pinpoint the intestinal mucosal immune system as a key site of viral replication/persistence and CD4 depletion, even in subjects with undetectable blood virus during therapy. These studies demonstrate that acute SIV and HIV infections are coupled with a dramatic and selective loss of memory CD4 T cells in lymphoid tissue, due to direct virus-induced cytolysis or immune-mediated mechanisms (Mattapallil JJ et al, Nature 2005; 434: 1093-7). Treatment strategies based primarily on blood viral load and circulating CD4 cell counts are hence misguided. These findings plead for HAART initiation as early as possible, and will also have implications for vaccine development.