Why the current drug therapy cannot restore the immune system function of some HIV patients?

Why the current drug therapy cannot restore the immune system function of some HIV patients?

Why the current drug therapy cannot restore the immune system function of some HIV patients?   A research report published in the international journal Journal of Virology, scientists from the University of Helsinki in Finland and other institutions have discovered through research that a kind of “The protein kinases involved in the body’s immune process may significantly promote immune deficiencies in HIV patients. Drugs that block these protein kinases may provide a strategy to treat HIV patients whose immunity cannot be restored through antiretroviral therapy. 

Antiviral drugs are usually used to treat HIV infection, and these drugs can inhibit the continuous progression of the disease. Although scientists have made great progress in HIV pharmacological treatment, the available drugs still cannot completely eliminate the virus in patients; however; About one-fifth of the HIV patients’ immune system does not recover as expected, that is, the number of CD4 T cells that reflect the state of the body’s immune system is still very low, even if the amount of HIV virus in the patient’s blood is suppressed to a very low level. Low levels or below the measured threshold; in such patients, researchers can detect indications of chronic immune activation that “erodes” the body’s immune system.

Image source: NIAID

Through joint research, scientists have now discovered that even if the proliferation of the HIV virus is successfully inhibited, the protein named Nef will be produced at a low level in the patient’s tissues for a long time. This protein is a central factor related to the HIV virus; The important significance of this immune erosion activity is the extracellular vesicle structure produced by Nef, which circulates in the blood and promotes the body’s chronic immune activation. In the article, the researchers discovered this special extracellular mechanism, which opens the chain of events related to the body’s immune activation.

The researcher Saksela explained that the study in this article shows that the Nef protein can initiate this harmful chain of events through special cellular signals (which can activate the Src protein kinase family), which leads to the activation of Raf and MAPK protein kinases. The protein kinase is activated, and the production of extracellular vesicles mediated by it will also begin. Pharmacological agents that inhibit Src, Raf, and MAPK protein kinases are currently in clinical use. In this study, researchers investigated their specific effects.

By studying this drug in tissue culture, the researchers observed that using the same drug level as the protein kinase inhibitor currently used in clinical practice, it may be possible to completely inhibit the production of inflammatory extracellular vesicles induced by Nef protein. .

Researcher Professor Saksela pointed out that relevant research findings may make it possible for scientists to explore new treatment methods, and it will not delay the current use of antiretroviral therapy to patients who cannot reverse the disease to a certain degree. Redirecting kinase inhibitors for the treatment of HIV infection seems to be a very promising way to solve this major medical challenge.

In recent years, Finland has about 150 new HIV infections each year. In the early 21st century, the number of new HIV infections per year remained below 200. In 2018, there were approximately 38 million HIV-positive people in the world, most of whom were infected. Africa region.

(source:internet, reference only)

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