Figure 4.

Innovative strategies against HAND. In the “Shock and Kill” approach, integrated pro-viral DNA is kicked into transcriptional activity by an LRA. The virally active cells will subsequently be eliminated with the continuation of antiretroviral therapy during the ‘kill’ phase. Several molecules, including epigenetic modifying agents such as HDACi, HMTi, and DNMTi, have been shown to reactivate the virus in vitro, ex vivo, and in vivo. The ‘Block and Lock’ strategy toward a functional cure aims to permanently silence the latent reservoir by utilizing latency-promoting agents (LPAs) to ‘block’ virus transcription and ‘lock’ virus promoters in a latent state via repressive epigenetic modifications. Stem cell transplantation involves a homozygous CCR5 delta32 stem-cell transplant into an HIV-1 infected patient with acute myeloid leukemia with the removal of antiretroviral treatment without subsequent viremic rebound. In the CRISPRCas9 system, dCas9-SAM minimally affects localized HIV-negative cells in latently infected microglial cells, promonocytes, and T cell lines. A Cas9/guide RNA system has been developed to eradicate the HIV-1 genome and immunize target cells against HIV-1 reactivation.