Despite outstanding improvements in morbidity and mortality following treatment with combination antiretroviral therapy (cART), currently available treatments do not cure HIV-1 and treatment is life-long. The major goal of research towards a cure for HIV-1 is to identify strategies that will lead to either a sterilising cure (elimination of all infected cells) or a functional cure (long-term control of HIV-1 in the absence of cART). The principal reason why cART cannot cure HIV-1 is latent infection in resting memory T-cell reservoirs. However, other long-lived cells such as brain astrocytes and cells of the macrophage lineage can also harbor latent HIV-1 infection. Understanding how HIV-1 infects and persists in cells of the central nervous system is therefore critical for development of strategies to achieve a cure for HIV-1.
Strategies currently being trialed to eradicate HIV-1 from latently-infected reservoirs include the use of transcriptional ‘activators’ that aim to activation latent viral transcription from integrated HIV-1, thus exposing infected cells for clearance by the immune system and/or cART. The CNS presents unique challenges when designing eradication strategies. It is an immune privileged site with altered penetration effectiveness of cART drugs. Importantly, we have shown that HIV-1 strains isolated from the CNS have unique transcriptional regulatory mechanisms that are likely to impact the effectiveness of current cure strategies. The potential impact of these unique regulatory mechanisms on cure strategies, in particular in relation to strategies concerning the CNS will be discussed.