Targeting persistent HIV infection: where and how, if possible?

Abstract

Sanctuaries of persistent human immunodeficiency virus (HIV) infection, which are diverse and stillincompletely resolved, account for the incomplete clearance of HIV among infected persons with a long-standing history of highly active antiretroviral therapy-HAART use. Specifically, sanctuaries of both actively replicating, and latent-virus make-up a source of rebound-viremia in persons living with HIV/AIDS (PLWHA) who, either stop or default-from HAART, even when there was prior demonstrable effective viral suppression and attainment of undetectable viral loads (<50 copies HIVRNA/mlby ultrasensitive single copy assays). To sustain viral suppression, persons infected with HIV must hence indefinitely stay on HAART. Targeting sites of persistent HIV-infection therefore becomes a pivotal strategy towards achieving HIV therapeutic cure by way of HAART. In order to devise means to counter persistent HIV infection-we note that, one must understand where and how this occurs. A review of persistent HIV niches is presented here within a holistic frame work that recognizes HIV to hide both at the cellular (latent-infection) and anatomic (active-infection) levels. Accordingly, the potential models for anti-HIV persistence should consist of (a) mechanisms to exorcise or flush out non-expressed or repressed host genome integrated proviral DNA, and (b) drug delivery strategies to intensify HAART access to unreachable anatomic hide-outs. Novel approaches to, either prevent the primary integration of HIV DNA into host genomes or kill-off those cell types chronically infected with HIV, are sought.