Experimental Approaches for Eliminating Latent HIV.

Abstract

Antiretroviral therapy (ART) can reduce HIV viral loads to undetectable levels and prevent disease progression. However, HIV persists in rare cellular reservoirs within ART-treated patients and rapidly reemerges if ART is stopped. Latently infected CD4+ T cells represent a major reservoir of HIV that persists during ART. Therefore, a cure for HIV must include methods that either permanently inactivate or eliminate latent virus. Experimental methods under investigation for eliminating latently infected cells include transplantation/gene therapy approaches intended to deplete the infected cells and replace them with HIV-resistant ones, and DNA editing strategies that are capable of damaging or excising non-expressing HIV proviruses. Alternatively, "activation-elimination," also known as "shock and kill," approaches aim to induce expression of latent virus, allowing the virus to be eliminated by viral cytopathic effects, immune effector mechanisms, or additional cells/antibodies that specifically target and kill cells expressing HIV proteins. Here, we describe these experimental approaches for eliminating latent HIV along with other recent advances in HIV cure research.