“Flush and replace”: a new approach to HIV treatment is proposed

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You can use the natural mechanism for updating protective cells – CD4 + T-lymphocytes – which the virus infects. Article published In the magazine Trends in Immunology. Research supported by a grant Russian Science Foundation (RSF).

HIV affects cells of the immune system that have CD4 receptors on their surface. The virus attaches to these proteins, and as a result, the work of the immune system is inhibited and the acquired immune deficiency syndrome develops (AIDS), when the patient’s body loses its ability to defend itself against infections and tumors. Without medical intervention, patients die on average 9–11 years after infection. When conducting antiretroviral therapy, which includes taking several drugs, the patient’s lifespan can be extended to 70–80 years. At the same time, the concentration of free viruses decreases, but HIV-infected cells remain.

One of the mechanisms of resistance to HIV antiretroviral drugs in the form of a chronic infection is associated with the formation of hidden viral reservoirs, that is, the ability of viruses to be inactive (latent) form in infected cells for many months and even years. In this case, the virus does not multiply, it is hidden, does not enter the bloodstream, and therefore the medicine does not work. This reduces the effectiveness of the use of antiretroviral drugs, and the infected cell is not recognized by the immune system for subsequent destruction.

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As a possible approach focused on the elimination of latently infected cells, the so-called “activate and kill” strategy is considered. It is based on the use of drugs that activate viral development in latently infected cells. This makes the latter available for the destruction of CD8 + T cells of the immune system and increases the effectiveness of antiretroviral therapy. There are drawbacks to this approach: the toxicity of drugs, the unpredictable reaction of infected cells, which can lead to their additional reproduction, as well as the effect of suppressing T-cell activity.

The authors of the new article suggest a different approach – “rinse and replace”. Scientists conducted a systematic analysis of a wide variety of data on the development and structure of the HIV population in the human body before and during antiretroviral therapy. This approach was formulated through studies on changes in the characteristics of HIV infection in humans and monkeys.

The proposed approach is based on the use of the natural mechanism for maintaining T-cell homeostasis (constancy). It is associated with leaching of a portion of activated subpopulations of more mature lymphocytes, including latently infected CD4 T cells. This occurs due to the entry of less differentiated cells into the organs where immune cells (lymphoid) are born and their competition for survival factors.

“Through the use of additional polyclonal activation of T cells in combination with standard antiretroviral therapy, the process of updating the T cell population can be accelerated. This is our working hypothesis, which postulates the possibility of implementing a new approach to the removal of all latently infected cells, ”- tells Gennady Bocharov, one of the authors of the article, project leader on a grant from the Russian Science Foundation, leading researcher, doctor of physical and mathematical sciences, employee of the G.I. Marchuk Institute of Computational Mathematics, Russian Academy of Sciences.

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