Even with effective antiviral treatment, living with HIV can lead to a premature aging of the immune system and a persistent state of immune activation. Now, research from Linköping University in Sweden suggests a potential path toward improving the health of people living with HIV: repurposing an existing medication. A recent study, published in the journal PLOS Pathogens, reveals that an approved drug can restore key immune cell function in laboratory settings, offering a promising avenue for future investigation.
For decades, antiretroviral therapy (ART) has dramatically transformed HIV from a death sentence into a manageable chronic condition. ART works by suppressing the viral load – the amount of HIV in the blood – to undetectable levels. However, the virus can remain hidden in reservoirs within the body, and even with successful viral suppression, the immune system often remains dysregulated. This chronic immune activation contributes to a range of health problems, including cardiovascular disease, kidney disease, and certain cancers, increasing morbidity and reducing quality of life for those living with HIV. Understanding how HIV disrupts the immune system, even when controlled by medication, is crucial to finding new therapeutic strategies.
How HIV Hijacks the Immune System
The research team at Linköping University focused on the role of type I interferon, a protein central to the body’s initial response to viral infections. In a healthy individual, when a virus is detected, type I interferon is activated, triggering a cascade of immune responses to fight off the infection. Once the threat is neutralized, interferon levels return to baseline. However, the researchers discovered that HIV exploits this highly system, causing a chronic activation of type I interferon signaling even when the virus is suppressed by ART.
“In the case of an HIV infection, type I interferon provides protection in the first stage when the body gets infected,” explains Cecilia Svanberg, postdoctoral fellow at Linköping University and lead author of the study. “But if the interferon is chronically activated, an overactivation of the immune system will instead facilitate the spread of HIV in the body.” This persistent activation leads to immune exhaustion, diminishing the effectiveness of critical immune cells like dendritic cells and T cells.
Dendritic cells act as messengers, presenting viral antigens to T cells to initiate an immune response. T cells, in turn, directly kill infected cells and coordinate the immune system. When these cells turn into exhausted, the body’s ability to fight off infections and maintain overall health is compromised. The study pinpointed that the chronic interferon activation occurs specifically when dendritic cells and T cells interact, highlighting a potential target for intervention.
Restoring Immune Function with an Existing Drug
The breakthrough came when the researchers tested the effects of anifrolumab, a medication already approved for the treatment of systemic lupus erythematosus (SLE), an autoimmune disease. Anifrolumab works by blocking the type I interferon receptor, effectively dampening down the overactive immune response.
“When we treated the cells with a medication currently used to treat another disease, this perfectly restored the function of the immune cells. It looks just like when HIV is not present,”
Cecilia Svanberg, postdoctoral fellow, Linköping University
The results were striking. Treating the cells with anifrolumab reversed the effects of chronic interferon activation, restoring the function of both dendritic cells and T cells to levels comparable to those seen in the absence of HIV. Further supporting this approach, other research groups have conducted preclinical studies in animal models with HIV-like infections. These studies, using anifrolumab or similar interferon blockers, have shown a reduction in viral load and improvements in overall health. A 2023 review in Viruses details several such studies, highlighting the potential of interferon inhibition as an adjunct therapy for HIV.
What’s Next for HIV Treatment?
“Using this interferon blocker together with existing antiviral treatment could possibly improve the health of people living with HIV,” says Marie Larsson, professor of virology at Linköping University, who led the study. “We feel it would be worth investigating further.” The researchers emphasize that this is still early-stage research, conducted in cell cultures. Clinical trials are needed to determine whether anifrolumab, or similar drugs, can safely and effectively improve immune function and long-term health outcomes in people living with HIV.
The Swedish Research Council and Region östergötland provided funding for this study. Researchers are now planning further investigations to explore the optimal dosage and timing of anifrolumab in combination with ART, as well as identifying biomarkers that could predict which individuals might benefit most from this approach. The potential to repurpose an existing medication offers a faster and more cost-effective pathway to new therapies compared to developing entirely new drugs.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
The findings represent a significant step forward in understanding the complex interplay between HIV and the immune system, and offer a glimmer of hope for improving the long-term health and well-being of the millions of people living with HIV worldwide. The next step will be to translate these promising laboratory results into clinical trials, bringing us closer to a future where people with HIV can not only live longer, but too live healthier lives.
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