• Research indicates that metformin could help reduce the viral reservoir in HIV patients.
• Metformin is currently used in the treatment of type 2 diabetes.
• It appears to reduce inflammation, which could reduce metabolic disease risk.
• It may also make it more difficult for HIV to evade the immune system.
• In the future, metformin might be used to make antiretrovirals more effective.

Canadian researchers say the type 2 diabetes drug metformin could help to reduce the viral reservoir — or even clear it out completely — in people living with human immunodeficiency virus (HIV) who also are undergoing antiretroviral therapy.

The authors of the September 2024 study, which was published in the journal iScience, state that in previous studies, when people took the drug for three months, there were improvements in immunity and reductions in inflammation.

In the current study, they found that metformin increased the number of cells with the HIV virus while preventing the virus from leaving the cells.

They note that these effects could be used to boost the effects of antiretrovirals.

This is significant because antiretroviral therapy can reduce the virus’s replication to undetectable levels, but it does not completely eradicate it.

Although these drugs can improve people’s quality of life, the remaining viral reservoir can lead to chronic inflammation and associated diseases such as cardiovascular disease, cancer, and metabolic disorders.

How metformin might work to reduce HIV viral reservoirs

The authors explain that metformin is capable of inhibiting the activity of the mechanistic target of rapamycin (mTOR) molecule.

In their study, this inhibition helped slow down HIV replication in the CD4+ T lymphocytes that harbored them, indicating that metformin could help to reduce a person’s viral load.

The researchers explain that metformin also causes the overexpression of the BST2 protein, which helps to tether virions (the infectious form of the virus) to the surface of infected cells.

This allows the immune system to locate them and send antibodies to attack them.

Edwin Bosa-Osorio, MD, a primary care physician and a faculty member in the Family Medicine Program at The Brodes H. Hartley, Jr. Teaching Health Center at Community Health of South Florida, Inc. (CHI), commented on the study, explaining how metformin could exert its effects.

“Metformin does this by helping boost the number of HIV-infected cells so as to help expose them to the HIV medication,” he explained. “So, metformin seems to be helping the HIV medication work more efficiently.”

However, Bosa-Osorio, who was not involved in the study, cautioned that these studies have only been done in a laboratory.

“So, in reality, the proof must be in the pudding,” he said, “which is to say that clinicians need to move to clinical trials that can tell us more about whether what they are seeing in vitro is applicable to actual patients.”

John Lowe, MD, a Physician at Restore Care who was not involved in the study, said that while metformin is primarily used to lower blood sugar in people with type 2 diabetes, it is also effective as an anti-inflammatory.

“In HIV, inflammation matters since it is instrumental in viral persistence, and metformin may help dampen this inflammation assisting the virus to escape,” he said.

Lowe added that this reduction in immune activity could make it harder for the viral reservoirs to persist.

“Apart from that, metformin may be beneficial in HIV treatment since it decreases insulin resistance, thereby decreasing the chance of adequate conditions for HIV reproduction,” he stated.

What this might mean for the future of HIV treatment

If future investigations bear fruit, this could alter the way that HIV therapy is managed, according to Lowe.

“Present-day therapies are effective in viral replication suppression, but there is no eradication of the virus. Hence, the patient requires medication for the rest of his life,” he said.

Lowe further commented that metformin has a positive safety record and could make HIV treatment cheaper.

It would also widen the range of possible treatments for the disease, he added, and it could decrease the number of drugs used in some people, for example, those with diabetes.

“If the results of antiretroviral therapy were positive, it would not be surprising if Metformin went further still,” he said.

“This study suggests the possibility of using metformin to get a faster response to the medications we currently use for controlling HIV,” added Bosa-Osorio.

He explained that it’s not going to replace those medications, however, since it doesn’t appear to directly affect the virus, although it could make antiretrovirals more efficient.

“And because metformin also has an anti-inflammatory effect, it can also help reduce cardiovascular conditions that HIV patients are prone to have because HIV is a pro-inflammatory disease,” Bosa-Osorio concluded.

Takeaway

A new study reports that the type 2 diabetes drug metformin could help people living with HIV who are using antiretroviral drugs.

In a previous study, after three months of using metformin, people had reduced inflammation and improved immunity.

This is important since the chronic inflammation associated with HIV puts patients at greater risk for cardiovascular disease, diabetes, and metabolic disorders.

Metformin also appears to create immune system changes that make antiretrovirals more efficient at reducing the viral reservoir.

While this has only been demonstrated in a lab so far, experts say metformin could someday become a valuable adjunct to antiretroviral therapy.