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Study Shows that Premature Aging in People with HIV is Caused by the Infection Itself, Not Just Antiretroviral Treatment

People with HIV have altered levels of a specific RNA molecule related to both aging and inflammation. This molecule remains altered even with antiretroviral treatment, indicating that their immune system remains affected despite receiving antiretroviral treatment and controlling the infection.

The authors of the study, published in the Journal of Microbiology, Immunology, and Infection, suggest that the origin of this alteration is chronic inflammation caused by the infection, regardless of the treatment received by patients.

Having this marker can be helpful in monitoring the evolution of patients and the effectiveness of the drugs they take to restore the normal functioning of their immune system.

People infected with HIV, nearly forty million worldwide, experience premature aging associated with various pathologies such as neurocognitive disorders, cardiovascular health issues, and diseases affecting the liver and bones. A recent study by the Hospital del Mar Research Institute has validated a biomarker for this process, making it clear that the origin of this impairment is the infection itself, regardless of the treatment to stop it. The work, involving researchers from the CIBER in Frailty and Healthy Aging (CIBERFES) and the CIBER in Infectious Diseases (CIBERINFEC), is published in the Journal of Microbiology, Immunology and Infection.

Authors of the study. From left to right: Juan Du, Robert Güerri, Natàlia Garcia-Giralt, and Xavier Nogués

The study's results could provide a valuable tool for monitoring patients' progress, their inflammatory state, and the effects of the drugs administered on their immune system. To do this, researchers analyzed the levels of microRNA molecules, small RNA molecules that modulate the expression of other genes, in the blood of people with HIV. They found that one molecule, miR-21-5p, was significantly elevated. This molecule is associated with inflammation as well as oxidative stress, leading to accelerated aging.

A Viable Marker in Elite Patients as Well

To confirm the hypothesis, the study compared the levels of this marker with a group of healthy individuals and another of 'Elite' patients. These patients are a minority group of people infected with HIV who spontaneously control the infection. In their case, they also have altered miR-21-5p, suggesting they have chronic inflammation despite controlling the infection. The fact that this group also has elevated levels of this biomarker confirms that the origin of this alteration lies in the infection itself and not in the antiretroviral treatment received by people with HIV.

All of this leads Dr. Natàlia Garcia-Giralt, a researcher at the Musculoskeletal Research Group of the Hospital del Mar Research Institute and CIBERFES, to state that with this work, "we demonstrate that there is a biomarker related to inflammation that shows us that patients with HIV infection will always have an altered immune system, despite antiretroviral treatment." At the same time, she points out that now "we have a tool that shows that these people, whether they are administered antiretroviral treatment or control the infection themselves, continue to have chronic inflammation that causes premature aging."

The researchers believe that the marker's alteration is due to the changes that HIV infection induces in the immune system of those living with it. In this regard, Dr. Robert Güerri, head of the Infectious Diseases Service at the Hospital del Mar, researcher at the Hospital del Mar Research Institute and CIBERINFEC, and associate professor at Pompeu Fabra University, explains that "this biomarker is one of the factors contributing to the chronic, continuous, and persistent inflammation in patients infected with HIV. Also, antiretroviral treatment is incapable of reversing this pathway, contributing to maintaining chronic inflammation, which may explain their premature aging."

"This study shows us that despite controlling the infection with antiretroviral treatments, HIV leaves a persistent mark on people living with it," notes Dr. Güerri. For this reason, monitoring the evolution of this biomarker can be a valuable tool for assessing the success of treatments in these individuals, as a return to normal levels would indicate the normalization of their immune system and the inflammation caused by its activation in response to HIV infection.

The work has received support from an FIS project of the Carlos III Health Institute, Ministry of Science and Innovation (grant number PI19/00019), CIBERFES (CB16/10/00245), and CIBERINFEC (CB21/13/00002).

Reference Article:

Meseguer-Donlo J, Soldado-Folgado J, Du J, González-Mena A, Blasco-Hernando F, Cañas-Ruano E, Nogués X, Knobel H, Garcia-Giralt N, Güerri-Fernández R. HIV infection is associated with upregulated circulating levels of the inflammaging miR-21-5p. J Microbiol Immunol Infect. 2023 Jul 31:S1684-1182(23)00130-5. doi: 10.1016/j.jmii.2023.07.011. Epub ahead of print. PMID: 37562995.

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