The latent reservoir for HIV-1 in resting CD4+ T cells and other viral reservoirs during chronic infection: insights from treatment and treatment-interruption trials

Abstract

Purpose of review: Although treatment of HIV-1 infection with highly active antiretroviral therapy can decrease virus in the plasma to undetectable levels, it cannot eradicate the infection due to the existence of viral reservoirs. These reservoirs are cell types or anatomic sites in which replication-competent virus persists without significant decay over time. This article reviews several proposed reservoirs for HIV-1 and their clinical significance.

Recent findings: Recent advances allow formal genetic delineation of viral reservoirs and compartments. The best-understood reservoir is a small pool of resting memory CD4 T cells carrying a quiescent form of the HIV-1 genome integrated within active cellular genes. Turnover of these cells is extremely slow, consistent with their function in immunologic memory. Latently infected memory CD4 cells that become reactivated release replication-competent HIV-1 which can be detected in the plasma and which can restore high levels of viremia if treatment is stopped. This reservoir can store drug-resistant virus if it arises, thereby permanently limiting treatment options. Evidence for other cellular reservoirs, including monocytes and macrophages, and for anatomical reservoirs including the genital tract and the central nervous system, is also discussed.

Summary: Recent advances in characterizing cellular and anatomic reservoirs and compartments influence approaches to antiretroviral treatment, the management of antiretroviral resistance, and potential eradication strategies. The study of long-lived viral reservoirs is critical to the understanding of chronic HIV-1 infection and to the ongoing search for a cure.