Application of RVX-208 used as HIV-1 latent infection reversal agent

Abstract

The invention discloses the application of RVX-208 as an HIV-1 latent infection reversing agent, belongs to the field of medicine, and relates to the application of RVX-208 (Apabetalone, RVX-000222) as an HIV-1 latent infection reversing agent. An important reason why HIV‑1 is difficult to be completely eliminated in the body is that HIV‑1 can lurk in the resting memory CD4 + in T cells. The RVX-208 of the present invention has good activity of activating HIV-1 latent cell pool in vitro, especially can efficiently activate the latent virus pool in HIV-infected patients, and can activate latent infection reversal agents such as protein kinase C with other mechanisms of action Drugs, histone deacetylase inhibitors and cytokines have a good synergistic effect. Compared with the known BET inhibitor JQ1, its in vitro cytotoxicity is greatly reduced, and the drug is safe and well tolerated. Therefore, RVX‑208 is expected to become a new and efficient HIV‑1 latent infection activator, so as to achieve the goal of completely eradicating the HIV‑1 latent infection pool and realizing the "functional" cure of HIV.

Description

technical field [0001] The present invention relates to a new application of compounds, in particular to the application of RVX-208 (Apabetalone, RVX-000222) as an HIV-1 latent infection reversing agent. technical background [0002] AIDS is caused by human immunodeficiency virus (human immunodeficiency virus, HIV), the most serious single-cause disease in humans, characterized by severe damage to the systemic immune system. As of 2014, the number of people infected with HIV worldwide has reached 36.9 million, which seriously threatens human health and survival. In 1996, the successful application of highly active antiretroviral therapy (HAART) or combination antiretroviral therapy (cART) transformed AIDS from a fatal disease to a chronic and manageable disease , greatly prolonging the survival time of AIDS patients. As of June 2015, 15.8 million people worldwide have received cART treatment. However, since the development of cART, it also has its insurmountable limitatio...

AI Technical Summary

Problems solved by technology

[0008] Unfortunately, the above-mentioned candidate LRAs for the treatment of HIV latent infection are still only in the clinical trial stage, and breakthrough progress has not yet been made. They have more or less certain defects, which limit their wide application in clinical practice.

The main issues are as follows: 1) Some epigenetic therapy drugs can also cause many side effects while activating the virus. For example, the mechanism of HDAC inhibitors is controversial, and nausea, vomiting, and blood system abnormalities have also been reported in clinical practice. and affect the normal function of genes, etc.; 2) PKC activators can affect the transcription factor signaling pathway of normal T cell activation, resulting in complex immune and chemical drug clearance leading to the latent virus reservoir; 3) Some drugs have poor specificity and Extensive, high toxicity and side effects, not suitable for long-term application, etc.

4) Many of the above-mentioned LRAs are still in the stage of clinical trials, and even some drugs have only been confirmed to activate latent viruses in in vitro cell experiments, and there is still a long way to go

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