Scientific rationale for antiretroviral therapy in 2005: viral reservoirs and resistance evolution

Abstract

Hope for a cure for HIV-1 infection was dampened by the discovery of a latent form of the virus that persists in resting CD4+ cells. This reservoir of latently HIV-infected resting memory T cells represents an archive of viral genotypes produced in an individual from the onset of infection. Entry into the reservoir is stopped with suppressive antiretroviral therapy, but the archived viruses are capable of re-initiating active infections, are released continuously from this reservoir, and can cause viral rebound if antiretroviral therapy is stopped. Studies of residual low-level viremia (<50 HIV RNA copies/mL of plasma) in the setting of effective antiretroviral therapy indicate that such viremia is largely caused by activation of the latently infected cells and the release of virus from this and other stable reservoirs. These studies support the notion that the stability of the latent reservoir is consistent with the long life span of resting memory T cells, rather than reflecting rounds of active replication under suppressive antiretroviral therapy that replenish the reservoir. There may be other stable reservoirs in addition to the resting T-cells pool, further complicating the problem of eradication. This article summarizes a presentation on viral reservoirs and viral evolution by Robert F. Siliciano, MD, PhD, at the International AIDS Society-USA course in New York in March 2005.