HIV Experts Discuss Inflammation and HIV

Some experts call it inflammation, others call it immune activation. What they all agree on is that it's chronic and it must be reduced. Three healthcare providers sound off on the mounting evidence of interactions between inflammation and HIV.

Paul MacPherson

Specialist in Infectious Diseases
The Ottawa Hospital

With effective antiretroviral therapy (ART), many people with HIV can now anticipate a near-normal lifespan. Looking back over the past 20 years, where we are today can only be considered a triumph of modern medicine. However, as people with HIV live longer, new challenges in treatment and care are coming to light. Chronic inflammation is likely central to many of these challenges.

Whether this is inflammation in the classic sense (think of the redness and swelling associated with an infected cut) or better described as chronic (long-term) activation of the immune system is a matter of debate among immunologists. Regardless, it is clear that even with effective ART the immune systems of people with HIV show signs of persistent activation.

What drives this immune activation remains unclear. One possibility is ongoing, low-level HIV replication in various places in the body that ART drugs cannot reach. Different parts of the body can have different levels of HIV suppression based on the virus' ability to replicate, how well drugs can get to that part of the body and the body's ability to fight HIV there. There is now clear evidence that an undetectable viral load in the blood does not ensure that HIV is not replicating to some degree in other tissues.

While persistent low-level HIV replication could drive ongoing immune activation, it is also possible that this immune activation drives HIV replication, setting up a vicious cycle. Another potential explanation for chronic inflammation in people with HIV is the fact that bacteria and associated proteins can "leak" into the blood from the gut and activate the immune system. Other explanations include co-infection with CMV (cytomegalovirus) and problems in the regulation of some cytokines, chemical messengers in the body.

Regardless of the underlying cause or causes, the effects of chronic immune activation are only now starting to be recognized. Evidence suggests a strong link between chronic inflammation and the development of heart disease. Other possible outcomes may include brain and cognition problems, premature aging and even kidney dysfunction.

Much research still needs to be done to better understand the long-term effects of chronic inflammation, what is driving it and how to reverse it. If the past 20 years are any indication, these challenges will not be insurmountable.

Inflammation 101

Inflammation is part of your body's response to injury or infection. Under the right circumstances it is beneficial to the body, as we could not heal without it. There are two types of inflammation: acute, which tends to be time-limited, and chronic, which is more of an ongoing process. Chronic inflammation causes damage to tissue, as well as ongoing pain, scarring and an accumulation of white blood cells. Fighting a long-term chronic infection like HIV throws the immune system into an ongoing state of activation, or chronic inflammation.

Marianne Harris

Clinical Research Advisor
HIV/AIDS Research Program, St. Paul's Hospital
Vancouver

Any type of chronic infection, such as HIV or hepatitis B or C, will activate the immune system and cause chronic inflammation. Over the long term, inflammation damages the blood vessels and organs, increasing your risk of conditions like heart, kidney and lung disease.

Treating HIV infection with antiretroviral therapy greatly reduces inflammation but does not get rid of it completely, so people living with HIV are at increased risk of these other conditions.

If you have HIV, the best way to reduce inflammation and decrease your risk of these conditions is to take antiretroviral therapy consistently and continuously. You should also receive treatment for hepatitis B or C, or any other chronic infections you may have.

Another important way to reduce inflammation is to quit smoking. Smoking tobacco increases inflammation throughout the body, increasing your risk of heart, kidney and lung disease as well as osteoporosis (weakened bones) and many cancers.

What else can you do to reduce inflammation? Obesity and stress can increase inflammation, so it's important to maintain an ideal weight by eating a healthy diet and getting regular exercise. Coping with stress and getting enough sleep are likewise important for reducing inflammation and maintaining overall good health.

Should you be taking antioxidant supplements or enriching your diet with foods that are high in antioxidants? My advice to patients is no. With the exception of vitamin D, there is no evidence that taking antioxidants will decrease your levels of HIV-related inflammation, improve your health or increase your lifespan. In fact, high levels of some antioxidants (beta carotene, vitamin E and possibly vitamin A) may be associated with an increased risk of death.

There is some evidence that adequate levels of vitamin D are associated with a lower likelihood of several inflammatory conditions, including heart disease, diabetes, bone disease and certain cancers. The ideal amount of vitamin D for people with HIV is unknown, but a daily intake of 1,000 to 2,000 international units (IU) of vitamin D3 is probably enough and certainly safe. Vitamin D supplements are inexpensive and can safely be taken with antiretroviral drugs.

Tasleem Kassam

Naturopathic Doctor
Effective Health Solutions
Calgary

Several studies suggest that chronic HIV infection creates a state of premature aging and inflammation that can lead to other chronic diseases. Here is the advice I give to my patients for reducing inflammation:

Eat well. Aim for a diet rich in colourful vegetables and lean protein, with moderate amounts of grains, legumes, nuts, seeds and fruit. Protein, the building block of antibodies, is important for a healthy immune system. Supplement with protein powders if needed. Avoid trans fats, refined carbohydrates and processed foods as much as possible.

Both the cause of HIV-related inflammation and the best way to treat it remain uncertain. A Canadian study, called the MAINTAIN study, is expected to reveal more about the role that antioxidants and other supplements play in helping the immune system of people living with HIV. To learn more about this study, go to www.hivnet.ubc.ca.

Manage stress. Stress and inflammation both play a role in cardiovascular disease. To keep your stress to a minimum, do deep-breathing exercises, yoga or Tai Chi and journal regularly.

Exercise. While exercise is good, extreme workouts can cause muscle damage and actually increase inflammation. Moderation is the key.

Mix up the antioxidants. Any antioxidant is going to help repair the damage caused by free radicals, molecules that are produced within cells. I suggest that people get a mix of fat- and water-soluble antioxidants, such as curcumin, astaxanthin with mixed carotinoids, and vitamins C and E (mixed tocopherols).

Take probiotics. The right mix of friendly bacteria in your gut helps to keep your digestive tract healthy and benefits many other organ systems too.

Sleep. Most of us are sleep deprived without realizing it. To prevent a surge of inflammatory hormones, make healthy and regular sleep habits a priority. Aim for a minimum of eight hours nightly.