Reservoirs of human immunodeficiency virus type 1: The main obstacles to viral eradication

Highly active antiretroviral therapy (HAART) has led to profound decreases in morbidity and mortality rates in human immunodeficiency virus type 1 (HIV-1)-infected persons, at least in the developed world. Many infected persons have plasma levels of HIV-1 RNA that are less than the limits of detection of most clinical assays as a result of combination antiretroviral therapy. Nonetheless, HIV-1 has not been eradicated by HAART. This has been shown to be because of latent HIV-1 replication-competent provirus in resting CD4(+) T lymphocytes, cryptic viral replication below the limits of detection of most clinical assays, and, possibly, the presence of viral sanctuary sites. An understanding of these reservoirs for HIV-1 in the setting of virally suppressive HAART will be critical for the development of new approaches to induce HIV-1 remissions and for the exploration of the possibility of viral eradication in the future.