Future approaches to clearing the latent human immunodeficiency virus reservoir: Beyond latency reversal

While combined antiretroviral therapy (cART) allows near-normal life expectancy for people living with human immunodeficiency virus (HIV), it is unable to cure the infection and so life long treatment is required.

The main barrier to curing HIV is the latent reservoir of cells, which is stable and resistant to cART.

Current approaches under investigation for clearing this reservoir propose a 'Shock and Kill' mechanism, in which active replication is induced in latent cells by latency reversal agents, theoretically allowing killing of the newly active cells.

However, previous studies have failed to achieve depletion of the T central memory cell reservoir, are unable to target other latent reservoirs and may be causing neurological damage to participants.

Future approaches to clearing the latent reservoir may bypass latency reversal through the use of drugs that selectively induce apoptosis in infected cells. Several classes of these pro-apoptotic drugs have shown promise in in vitro and ex vivo studies, and may represent the basis of a future functional cure for HIV.