Fat Tissue

In an era of highly effective drugs for HIV, patients have been living longer with their infection under control.

But in spite of the success of this type of antiretroviral therapy, the virus is never fully eliminated, and patients often experience ongoing inflammation in their body.

Recent research in both monkeys and people suggests that adipose tissue — best known as a storage place for fat — may have a hand in both of these.

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Overlap Between HIV and Obesity

Weight gain in parts of the body is a common problem among people undergoing therapy for HIV.

“It’s been known for a while that when patients start antiretroviral therapy, they tend to gain visceral adipose tissue,” Dr. Peter Hunt, associate professor of medicine at the University of California, San Francisco, Division of HIV/AIDS at San Francisco General Hospital, said in an interview with Healthline.

This extra fat can show up in the abdomen, neck, breasts, and face. The effects of the fat also go beyond physical appearance.

“Even in HIV-uninfected individuals, obesity has long been known to be associated with inflammation,” said Hunt.

That led researchers to wonder whether the visceral fat gain seen during HIV treatment might contribute to the persistence of inflammation.

Obesity researchers have discovered that adipose tissue does more than just store energy as fat.

“If the adipose tissue isn’t functioning properly, then you begin to have a lot of metabolic problems,” Dr. John Koethe, an assistant professor of medicine in the Division of Infectious Diseases at Vanderbilt University School of Medicine, told Healthline.

What this paper is really looking at is whether or not the same changes that we see in obesity … might also be occurring in HIV infection.
Dr. John Koethe, Vanderbilt University School of Medicine

These problems include diabetes, cardiovascular disease and lipid problems — conditions that can affect people being treated for HIV.

But while obesity researchers have been studying adipose tissue for decades, this tissue has only recently caught the attention of HIV researchers.

One paper by French researchers, published online today in PLOS Pathogens, is helping the HIV field catch up. The study looks at adipose tissue as a potential place for HIV to hide and also as a source of inflammation in patients.

“What this paper is really looking at is whether or not the same changes that we see in obesity — in terms of immune cells in the adipose tissue — might also be occurring in HIV infection,” said Koethe.

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Immune Activity in Adipose Tissue

How inflammation develops — or continues — in HIV patients on antiretroviral therapy is not well understood. It’s likely driven by many factors and possibly the drugs themselves.

To rule out the effects of the HIV medication, the French researchers looked at macaque monkeys infected with simian immunodeficiency virus (SIV), a virus similar to HIV that causes AIDS-like disease in certain nonhuman primates.

In SIV-infected monkeys “we observed features commonly associated with obesity-related inflammation,” wrote the authors of the paper.

This included greater activation of immune cells — such as T cells — in the adipose tissue. Similar changes were also seen in adipose tissue samples collected from HIV patients who had undergone elective abdominal surgery.

HIV Body Fat

“In SIV and HIV infection, there appears to be a change in the makeup of the adipose tissue, and the [immune] cells that infiltrate the adipose tend to be more inflammatory,” said Hunt, who was not involved in the study.

Another study, done with human tissue and published earlier this year in the journal AIDS, also found that adipose tissue may act both as a viral reservoir and as a source of inflammation.

The researchers “were able to pull out T cells from adipose tissue and detect HIV in them,” said Koethe, who was not involved in either study. However, he added, the study “really gets much more into how the types of immune cells in adipose tissue are changing in HIV patients. And that’s probably at the root of a lot of the diabetes and lipid problems that we’re seeing.”

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Fat Tissue May Harbor HIV

Even with current treatments, HIV can remain hidden inside the body, invisible to the immune system and out of the reach of antiretroviral drugs.

These viral reservoirs are located in the brain, lymph tissue, bone marrow, and other areas of the body, but fat tissue has been largely overlooked until recently.

Some earlier research did find HIV proteins in adipose tissue. And a few lab studies showed that adipocytes — fat storage cells — could be infected by HIV. But that fell short of knowing what goes on inside HIV patients.

“While [other researchers] were able to infect adipocytes with HIV in the lab,” said Koethe, “they haven’t really been able to show that this happens in actual humans.”

In the new study, French researchers were able to detect SIV in the adipose tissue of monkeys and HIV in the adipose tissue of people, including in the immune cells located there. And it turned out that the virus was not completely dormant.

If you were to stop HIV medicines in the individual, then the viruses in the fat are actually capable of restarting the infection.
Dr. Peter Hunt, University of California, San Francisco

“Not only do they see that there’s virus in the tissue,” said Hunt, “they’re able to confirm that the virus is actually capable of causing a new infection.”

Long-term, this type of viral reservoir is a potential source of new infection.

“If you were to stop HIV medicines in the individual,” said Hunt, “then the viruses in the fat are actually capable of restarting the infection.”

In terms of finding a cure for HIV — in which the virus is eliminated completely — adipose tissue may come into play.

For people whose HIV infection is well-controlled by antiretroviral therapy — and can expect to live a long life — this is less of a concern.

“A bigger issue for somebody who is on treatment is that those cells are probably playing a role in the adipose tissue inflammation,” said Koethe. “The consequences of that would be that those cells in the adipose tissue are likely contributing to metabolic disease in HIV.”

While future studies may confirm adipose tissue as a source of inflammation in HIV patients, more research will be needed to develop a treatment that targets this tissue.