The latent reservoir for HIV-1 in resting CD4+ T cells: a barrier to cure

Abstract

Purpose of review: Despite remarkable progress in the development of drugs that inhibit HIV-1 replication, eradication of the infection has not been achieved. The principal reason is that the virus can persist in stable cellular reservoirs, the best characterized of which is a small pool of latently infected resting memory CD4 T cells that carry a stably integrated viral genome. This review covers recent discoveries on the biology of this reservoir, particularly as related to efforts to eliminate it.

Recent findings: New studies suggest how the reservoir may be established during acute infection and define where the virus integrates in the human genome. In addition, the relationship between the latent reservoir and the residual low-level virus production that continues even in patients on optimal therapy is becoming clear. Several recent studies have described approaches for eliminating the latent reservoir. New insights into the biology of the reservoir are providing a context for understanding the enormous obstacles that must be overcome before the reservoir can be eliminated.

Summary: The latent reservoir presents a formidable therapeutic challenge because it allows the virus to persist as genetic information in the form of a stably integrated provirus in an inherently stable cellular compartment. Eradication is complicated by the fact that the virus can undergo exponential expansion once drug pressure is released. Thus eradication must be complete to be effective.