Exercise—Potential impact on inflammation and mood

As mentioned previously in this issue of TreatmentUpdate, HIV infection is associated with activation of the immune system and inflammation. This inflammation is only partially suppressed with ART. Scientists are not sure why chronic inflammation occurs in HIV-positive people who use ART but suspect that it may be due to at least one of the following:

• continued production of low levels of HIV deep within the body, in places such as lymph nodes and lymphatic tissues
• changes to the immune system caused by HIV
• the presence of other germs or other unknown factors

Researchers at the University of Rome (Italy) and in Atlanta (U.S.) have proposed that one potential method for helping to reduce excess levels of inflammation and dampen immune activation in HIV-positive people is exercise.

Uncovered by fat

The impetus for exploring the effect of exercise comes from scientists at Harvard University who pointed out the following trends among HIV-negative people:

• more people are becoming obese
• obesity affects the immune system and likely promotes inflammation
• obesity and inflammation appear to increase the risk for developing unhealthy outcomes such as type 2 diabetes, stroke, heart attack, unfavourable levels of fatty substances in the blood (cholesterol and triglycerides), depression, dementia and cancers of the breast and colon

Even if a person is not obese, research on obesity-related inflammation underscores a previously underappreciated connection between the immune system and metabolism.

Exercise or no exercise

Much research has been done with HIV-negative people and exercise, and scientists have found that exercise can have many beneficial effects, including reducing the risk for type 2 diabetes and cardiovascular disease.

Studies with HIV-negative people who do not exercise have found that they are at increased risk for developing chronic low-grade inflammation. The problem of inflammation arises because many people who do not exercise tend to build up fat deep within their belly. This fat, called visceral fat, wraps itself around vital organs and produces hormones and chemical signals that favour inflammation. These hormones and signals produced by visceral fat also affect the immune system.

Exercise in HIV-positive people

Scientists at several centres around the world have recently studied the impact of exercise with HIV-positive people and we now summarize such studies.

Brazil

Researchers at the University of Bahia in Brazil conducted a six-month randomized, controlled study with 63 HIV-positive participants. They assigned participants to one of the following interventions:

• one hour of supervised gym activity (stretching, weight training and aerobics) three times weekly and monthly nutritional counselling
• once-monthly workshops to discuss the importance of physical activity and to receive nutritional counselling

At the end of the study, participants who engaged in regular exercise had decreases in the following assessments:

• body fat
• waist size
• blood sugar levels

They also had increases in the following assessments:

• muscle size
• CD4+ cell counts (very modest)
• improvements in mood

Australia

Scientists at the Alfred Hospital in Melbourne conducted a randomized, controlled study with 35 HIV-positive men for six months that involved the following interventions:

• two one-hour supervised fitness classes (including both aerobic and weight training) per week
• unsupervised walking twice per week and attending a monthly group meeting

As with some other studies, participants who received supervised fitness training had improved cardiovascular health, quality of life and cognitive function.

Italy—Even brisk walking is good

Some HIV-positive people experience a lack of energy and/or become tired very easily.  Perhaps, for such people, a program of brisk walking may be more suitable. Researchers in Milan, Italy, enrolled 59 HIV-positive people and assigned them to one of the following interventions for 12 weeks:

• three one-hour sessions per week of brisk walking outdoors
• three one-hour sessions per week of brisk walking and three 30-minute sessions per week of weight training

At the end of this study, all participants had statistically significant decreases in their total cholesterol and bad-cholesterol (LDL-C) and in their waist size.

There were also significant decreases in levels of proteins in the blood associated with immune activation, including the following:

• interleukin-6 (IL-6)
• D-dimer
• high-sensitivity C-reactive protein (hsCRP)
• activated CD8+ cells

Thus, even modest levels of exercise can have a beneficial effect on inflammation.

Pleasure

People who engage in regular exercise report feeling good or even high afterward. The Italian researchers suggest that this is likely for at least the following reasons:

• Exercise can cause cells to produce chemical signals called endorphins. These have a similar effect to the pain reliever morphine. People who exercise regularly can also experience greater tolerance of pain because of the release of endorphins. These chemical signals are also used by cells of the immune system to communicate.
• Exercise causes the brain and other parts of the body to produce and release another group of chemical signals called neurotransmitters. Initially, scientists thought that these chemical signals were used only by brain cells to communicate; however, other cells are sensitive to neurotransmitters. For instance, upon initiating exercise, the body produces neurotransmitters to help the heart cope with exertion from exercise. Also, together with endorphins, neurotransmitters can help people better deal with anxiety and stress. Exercise has an added benefit—it helps the brain to transition to a more relaxed state that makes falling asleep easier.
• Experiments with HIV-negative people suggest that regular exercise can improve cognitive functioning. The precise way that exercise does this is not clear. Some scientists think that exercise can increase the size of certain parts of the brain. Other scientists have found that exercise can increase the production of chemical signals such as BDNF (bone-derived neurotropic factor). These signals are associated with the development of new brain cells and memory formation.

Based on these and other studies, more scientists are in favour of exercise programs for HIV-positive people so that fitness, quality of life, overall sense of well-being and reduction of inflammation can occur.

Long-term clinical trials are needed to assess the effects of exercise and other interventions on the overall health of HIV-positive people as well as measures of inflammation.

—Sean R. Hosein

REFERENCES:

1. d’Ettorre G, Ceccarelli G, Giustini N, et al. Taming HIV-related inflammation with physical activity: a matter of timing. AIDS Research and Human Retroviruses. 2014 Oct;30(10):936-44.
2. Jaggers JR, Hand GA, Dudgeon WD, et al. Aerobic and resistance training improves mood state among adults living with HIV. International Journal of Sports Medicine. 2014; in press.
3. Trøseid M, Ditlevsen S, Hvid T, et al. Reduced trunk fat and triglycerides after strength training are associated with reduced LPS levels in HIV-infected individuals. Journal of Acquired Immune Deficiency Syndrome. 2014 Jun 1;66(2):e52-4.
4. Garcia A, Fraga GA, Vieira RC Jr, et al. Effects of combined exercise training on immunological, physical and biochemical parameters in individuals with HIV/AIDS. Journal of Sport Science. 2014;32(8):785-92.
5. Longo V, Bonato M, Bossolasco S, et al. Brisk walking improves inflammatory markers in cART-treated patients. In: Program and abstracts of the 21st Conference on Retroviruses and Opportunistic Infections, 3-6 March 2014. Abstract 763.