A primer on the harms of HIV-related chronic
inflammation, what treatments are being researched and what you can do
to reduce inflammation and improve your long-term health
April 5, 2016
•
By
Benjamin Ryan
Antiretrovirals (ARVs) have added decades to the life spans of people
living with HIV who have access to treatment. Nevertheless, when
compared with HIV-negative people, those taking treatment for the virus
still have a higher risk of various health problems typically associated
with aging. The reasons behind these increased health risks still
aren’t very well understood, but the scientific community is eagerly
looking for answers. Researchers are inclined to point the finger at a
phenomenon known as chronic inflammation as a main culprit.
When
you get a cut or infection, your immune system jump-starts a cascading
process that sends to the site a diverse army of cells that promote
healing and infection control and give rise to inflammation. Included in
this complex, interconnected battalion are CD4 and CD8 cells (known as
“helper” and “killer” T-cells), antibodies, clotting factors and
pro-inflammatory cytokines, among many others.
Normally,
certain cells will turn off this healthy inflammatory process when the
healing or infection-fighting process is complete. But sometimes,
inflammation persists over the long term and can become
counterproductive, causing damage to healthy cells and tissues. In
HIV-negative people, chronic inflammation is tied to a host of diseases,
including cardiovascular, autoimmune, liver and kidney diseases and
cancer.
HIV itself appears to give rise to chronic
inflammation. The virus also leads to dysregulation of the immune
system, which can further fuel inflammation. Many scientists believe
that HIV-related chronic inflammation contributes to HIV-positive
individuals’ increased risk of cardiovascular disease, neurocognitive
disease, osteoporosis (bone loss), liver disease, kidney disease,
frailty and some non-AIDS-defining cancers. These are all conditions
associated with getting older. People with HIV tend to get them at
younger ages than their HIV-negative counterparts.
Within weeks of infection,
HIV begins a massive assault on the gut, which has a high concentration of CD4 cells. Even very early treatment of the virus
may not totally reverse this damage,
which appears to cause chronic inflammation by allowing harmful
microbes to seep into the body (in a process called microbial
translocation), thus spurring more immune activation and chronic
inflammation.
While HIV treatment does help fight the
immune dysfunction and chronic inflammation caused by the virus, ARVs
don’t necessarily wipe out these effects. For one thing, having an
undetectable viral load doesn’t mean the virus is totally silent.
Low-level viral replication may still persist—and at a high enough level
to prompt a constant state of alert from the immune system, a chronic
inflammatory state. Consequently, over-activated immune cells may be
driven to a state of exhaustion, similar to what is seen in older
people. HIV may also disrupt the cells that turn inflammation on or off,
possibly compromising the body’s ability to properly regulate
inflammation.
People with HIV tend to have higher
rates of other viral infections, such as hepatitis B or C viruses (HBV,
HCV) and cytomegalovirus (CMV, which is in the herpes family), which may
also contribute to chronic inflammation and immune activation.
Additionally,
HIV may cause scarring in both the thymus and the lymph nodes, leading
to interference in the body’s ability to fight infections. The thymus is
an organ in the chest that is responsible for manufacturing T-cells,
while the lymph nodes are responsible for coordinating immune responses
to infections.
The numerous serious health problems to
which chronic inflammation could give rise may sound alarming. But
Steven Deeks, MD, a professor of medicine at the University of
California, San Francisco (UCSF), who is an expert in HIV-related
chronic inflammation, says, “It’s important to emphasize that the effect
that we’re talking about is not dramatic.” Such an effect, he says,
“will likely not have much of an impact on people’s quality of
life—their overall health, really—until people are in their sixth,
seventh decades of life, at which point in time it could very well be
much more apparent.”
Research into treatments for chronic inflammation:
“I
think the jury is still out whether the best approach is to target the
inflammatory response or rather to target the root drivers of the
inflammatory response: HIV itself, coinfections, microbial
translocation,” says Peter Hunt, MD, an associate professor of medicine
at UCSF who also studies HIV-related chronic inflammation. “One of the
problems is that we don’t really have successful interventions to block
those root causes; we don’t have any interventions that turn off HIV
expression.”
Several research studies
have suggested
that the cholesterol-lowering medications known as statins may lower
chronic inflammation among people with HIV and protect them against its
harmful effects. But results from a study that provides gold-standard
scientific evidence of such benefits from statins are still lacking.
Researchers are currently enrolling a planned 6,500 participants into
such a trial, called REPRIEVE. The study includes people with HIV who
are taking ARVs and who wouldn’t normally be in a position to take a
statin; they will be randomized to either receive a statin or a placebo.
The study will hopefully answer whether statins’ anti-inflammatory
effects will translate into a lowered risk of disease, such as heart
attack or cancer, among people with HIV. Unfortunately, results aren’t
expected until 2021.
Other on-the-market medications
currently under investigation as anti-inflammatory agents for people
with HIV include Micardis (telmisartan), a blood-pressure medication,
and the diabetes medication Vildagliptin (galvus). Research has already
shown that aspirin does not apparently help HIV-related inflammation.
Scientists
are also investigating to see whether probiotics, which promote
desirable bacteria in the digestive system, may affect the body’s
so-called microbiome in a way that helps lower gut-related inflammation.
Seeking
to directly affect inflammatory pathways, researchers are looking at
drugs used for inflammatory diseases, like the autoimmune disease
rheumatoid arthritis, and are even looking at some cancer treatments.
Other research is examining drugs that inhibit major indicators of
inflammation, called biomarkers, such as the cytokines interleuken-1 or
-6 (IL-1, IL-6).
Experts generally agree that a cure for HIV, if it is ever developed, remains decades away (contrary to
recent erroneous news reports).
In the meantime, as researchers strive to develop ways to shrink the
size of the viral reservoir and, in turn, likely reduce low-level viral
replication, they may wind up with treatments that, even if they don’t
cure someone, end up dampening chronic inflammation.
Things you can do to fight chronic inflammation and its potentially harmful effects:
According
to Deeks, the long-term damage caused by HIV-related chronic
inflammation may be easier to prevent when people are younger, as
opposed to reversing the damage once people are elderly.
Ways to prevent such damage include:
- Early treatment. Research has shown
that starting ARVs as soon after infection as possible reduces the
likelihood of health problems linked to inflammation, such as heart
attack and certain cancers.
- Take your ARVs every single day. Recent research found that anything less than 100 percent adherence was tied to higher inflammation.
- Don’t smoke.
Smoking is especially harmful among people living with HIV (not to
mention highly common) and can exacerbate inflammation in the arteries.
- Eat a healthy diet. Research has shown that the so-called Mediterranean diet reduces the risk of heart attack or stroke.
- Get moving. Regular exercise reduces your risk of numerous health problems.
- Shed body fat. Fat tissue may be a source of inflammation.
- Treat coinfections. Hep C is now curable through as little as eight weeks of treatment, and hep B is treatable. Both infections can cause severe damage to the liver; even well-treated HIV can accelerate such damage.
