HIV Latency: Novel insights into the viral reservoir and therapeutic strategies

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Background

The development of highly active antiretroviral therapy (cART) has significantly changed the perception of HIV/ AIDS from a fatal to a manageable chronic disease for those with access to treatment. Several studies have reported a strong positive association between cART and improved quality of life. Besides that, the development of new potent ARVs and their combinations maintain suppression of plasma viremia in levels undetectable in PLWH but does not cure HIV-1 infection, and plasma viremia rebounds in most HIV-1-infected individuals when cART is interrupted. HIV-1 can persist as a stably integrated and replication-competent provirus. The best-understood cellular reservoir in resting memory CD4+ T cells isolated mainly from blood. However, other subsets of memory and functional T cells have been described as potentially cellular reservoirs, but more studies are needed to understand these reservoirs.
Further, myeloid cells, including tissue macrophages, have been described as an essential cellular reservoir in different organs, but these cells' persistence mechanisms remain unclear. When and how the latent reservoir is established, have been described in the acute phase. However, the decay of intact DNA over time in cART-suppressed HIV patients is not fully known. Since the barrier to cure is the persistence of latent HIV, targeting this persistent and transcriptionally silent virus is critical. More than a decade ago, the first case of HIV remission was described in an individual called Berlin patient. He was submitted to a stem cell transplantation from a donor containing a mutation of 32 base pairs deletions in the CCR5 gene and stayed in HIV remission for 12 years until he died in 2020. In the same year, the London patient was presented as the second case of HIV remission, and he is almost three years without cART. In 2022 was described as the first HIV remission case in a woman. She received a transplant of umbilical cord blood stem cells with a deletion of 32 base pairs in the CCR5 gene and supplemented with donor's stem cells from the bone marrow of an adult relative, and she has been HIV in remission since then. HIV cure using stem cell transplants is possible. However, it is essential to highlight that this approach is an invasive, complex, and risky medical procedure and still cannot be used as a strategy to scale up to the millions of PLWH. These efforts have provided many technological breakthroughs in understanding the underlying mechanisms that regulate HIV latency. Despite progress in stem cell transplantation, developing an effective and scalable cure for HIV-1 is still not possible. For this reason, understanding this process in different cellular and tissues reservoir are crucial to developing new strategies for the HIV cure.
We welcome papers on but not limited to the following topics: HIV aging and latency, application of gene-editing technology in HIV therapy, and new candidates targets for ART.

Keywords: HIV, latent HIV, virus, viral reservoir, therapeautics

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