Important long-COVID lessons from AIDS researchers

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  • COVID-19
November 23, 2025
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Many of the researchers who are now working to find treatments and a cure for long COVID spent many years working on treatments for HIV/AIDS. And while the viruses are very different from one another, there are a number of similarities that experts hope may lead to new diagnostic tests and treatments for long COVID.

Those new research efforts have already yielded some promising advances. For instance, much of scientists’ understanding of long COVID — specifically in researching biomarkers, viral persistence, chronic inflammation, and antiviral treatments — came from years of prior research into HIV. However, it took many years to get from HIV being a death sentence four decades ago to the chronic but manageable condition that it has become today.

“Our hope is that it won’t take as long as it did with long COVID because of what we learned from HIV, but these things don’t just happen instantly, it takes a lot of work,” said Igho Ofotokun, MD, a professor of medicine at Emory University School of Medicine, Atlanta, and a researcher in both HIV and long COVID.

Finding a Biomarker for Long COVID

Five years after long COVID was first identified, the single biggest roadblock in treating patients with the condition remains uncovering a biomarker that can be used to diagnose it. Without a clear tool for confirming positive diagnoses in patients, pharmaceutical companies are hesitant to fund clinical trials.

Still, finding a diagnostic blood test and then treatments for HIV also took time. The first blood test for HIV was approved by the FDA on March 2, 1985, nearly 5 years after the CDC reported the earliest deaths from AIDS. Reliable and safe treatments for HIV took much longer, with the first major antiviral breakthrough treatments developed in 1996.

Findings from 2023 found that certain biomarkers may identify long COVID with 80% accuracy. Researchers revealed that long COVID was associated with inflammation of the immune system in proteins such as C3, C4, and C5. But since then, a definite biomarker has not been identified.

Identifying Viral Reservoirs in HIV and Long COVID

At this point, we know that HIV spreads to organs and tissues in the deepest recesses of the body, called viral reservoirs, said Ofotokun. Researchers can also see that, similar to HIV, long-COVID symptoms result from multiple system organ damage. For example, people may have brain fog because there’s damage to the brain or shortness of breath because of damage to the heart and lungs.

“Long COVID seems to persist in the tissue of certain patients, meaning that some of us aren’t able to clear the virus,” said Grace McComsey, MD, an HIV researcher who leads one of the 15 nationwide long-COVID centers funded by the federal Researching COVID to Enhance Recovery Initiative in Cleveland. “HIV seems to hang out in the brain and gut, and we’re seeing the same patterns with long COVID.”

A study published last May in The Lancet Infectious Diseases points to treatments that target viral reservoirs in patients with long COVID.

“Recommendations are informed by knowledge gained from trials targeting the HIV reservoir,” which shared many of the same hurdles facing today’s long-COVID trials, wrote the study authors.

Using Antivirals as Treatments for HIV and Long COVID

Powerful antivirals reduce the viral load in the body enough to make HIV nontransmittable. But because the virus integrates into host DNA, it can’t be eliminated completely. That’s why researchers are yet to find a cure. Still, understanding HIV viral persistence has led to effective antiviral treatments, and researchers and experts hope this will also be true for long COVID.

“A lot of the lessons from HIV are that antivirals need to be a combination of the right dose to penetrate the affected tissue and also to prevent viral replication,” said W. Michael Brode, MD, an internal medicine specialist and assistant professor at Dell Medical School at The University of Texas at Austin.

He contended that these lessons are proving really important for how to design long-COVID clinical trials. For example, patients with HIV often take three antivirals each day at the same time to suppress the virus. Something similar may also be true for long COVID.

Researchers initially found that Paxlovid was an ineffective medication for the treatment of long COVID. Then, another study found that it was effective when it was used for longer periods. It’s about finding the right dose, interval, and drug combination.

“It could take higher doses and antiviral combinations to target viral reservoirs in patients with long COVID,” said David Putrino, PhD, director of rehabilitation innovation at the Mount Sinai Health System in New York City and a national leader in the treatment of long COVID.

Reducing Inflammation That Leads to Disease in Patients With Long COVID

HIV researchers know that the virus remains in a viral reservoir in the body, and they think this may be true for long COVID. In the case of HIV, low-level replication causes continuous stimulation of the immune system, which leads to chronic inflammation in patients with HIV, said Ofotokun.

What’s more, one result of chronic inflammation may be the early onset of disease. Patients with HIV may have shorter lifespans as a result of diseases related to chronic inflammation, including cardiovascular disease, diabetes, liver disease, and cancer.

This understanding of inflammatory-related disease in patients with HIV can also help researchers address similar conditions in patients with long COVID. For example, diabetes often occurs in patients with HIV, and research has shown that this is also true of patients with long COVID.

A recent study found that COVID-related inflammation may induce diabetes in some patients. Other research also found that the risk for type 2 diabetes went up based on the severity of an acute COVID.

Treatments for long COVID-related inflammation may include new trials for the use of GLP-1 receptor agonists, used to combat obesity.

“RECOVER TLC is looking at GLP-1 receptor agonists like Ozempic and others to walk back some of this vascular inflammation,” said Brode.

Another class of drugs, called JAK inhibitors, may also help block the activity of enzymes called JAKs and reduce long COVID-related inflammation in some patients, according to research published recently in BMC Neurology.

But in the end, without a long-COVID biomarker, it’s difficult to know how effective antivirals and anti-inflammatory medications are beyond what physicians hear from patient-reported outcomes, which don’t tell the whole story. To make progress like researchers did for HIV, they need to be able to test for the virus.

“If you want to measure the underlying activity of the disease and see what treatments are working, you have to have biomarkers,” said Brode.

By Sara Novak

 

Source : Medscape

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