Study finds fat goes up, muscle goes down over time

As all people age, they gradually lose muscle mass and probably gain some fat. Over decades, the loss of muscle mass can contribute to weakness and even frailty. Among HIV-negative people, this loss of muscle mass is initially small and tends to occur after the age of 50.

Studies of changes in body composition (usually such studies focus on the amount of fat and/or muscle in the body) in HIV-positive people have usually been short, rarely exceeding a monitoring period of 96 weeks. However, the restorative effects of HIV treatment (ART) on the immune system are so profound, that scientists increasingly expect many HIV-positive people to have near-normal life expectancy. Therefore, it is important that studies with HIV-positive people get the necessary funding so that they can continue for many years.

A team of scientists at the University of Modena in Italy has collaborated with other scientists in Canada, the U.S. and Portugal to analyse changes in body composition among ART users over the course of a decade. The scientists examined data from nearly 2,600 HIV-positive Italian people and found that muscle mass in the arms and legs “steadily declined.” Unlike what has been reported for HIV-negative people, the loss of muscle mass occurred even in HIV-positive people who were younger than 50 years old. Muscle loss occurred in both men and women.

The scientists also found that both men and women gained fat in their chest, abdomen and limbs during the same period.

The increase in fat in the body can contribute to a heightened risk for cardiovascular disease, diabetes and other problems.

The Italian study sounds an alarm that unfavourable trends are occurring among some HIV-positive people and interventions are needed so that the impressive gains in the survival brought about by ART are not lost to conditions affected by excess weight and fat.

Study details

Scientists began collecting data from ART users in Modena in 2004. As part of the study, technicians performed low-dose X-ray scans called DEXA (dual-energy X-ray absorptiometry) once or twice yearly for up to 10 years.

The average profile of participants upon entering the study was as follows:

• age – 44 years (90% of participants were younger than 50 years old)
• 1,759 men and 839 women
• 76% had an undetectable viral load as a result of taking ART
• current CD4+ count – 530 cells/mm³
• ever had a CD4+ count less than 200 cell/mm³ – 50% of participants
• history of AIDS-related weight loss – 5% men, 13% women
• duration of ART usage – 9 years
• all participants were white
• body mass index (BMI) – 23 kg/m²
• current smoker – 42%
• minimal exercise – 61%

The study collected data for up to 10 years, but most people were in the study for five years.

Results

Here are the key findings:

Muscle mass

Over the course of the study the amount of muscle tissue in participants consistently declined. This decline occurred in both men and women. Although the loss of muscle mass was more significant in people over the age of 50, it also occurred in people who were younger than 50 years old and, in some cases, people younger than 35 years of age. Loss of muscle tissue in relatively young HIV-negative people is unusual and the scientists found it striking that it occurred in young otherwise healthy HIV-positive people in their study.

On average men lost 322 grams and women 231 grams of muscle each year.

Factors associated with the loss of muscle mass included the following:

• among women – smoking and use of the older form of tenofovir (TDF, tenofovir disoproxil fumarate)
• among men – being older than 45 years, a history of AIDS-related weight loss and a CD4+ count that fell below the 200 cell/mm³ mark at some point in the past

Fat mass

Overall, scientists found that many participants gained fat over the course of the study. Furthermore, they noted: “These increases in fat mass were over and beyond those associated with ART initiation, and occurred in all age groups and across all ART classes and both sexes.”

The use of testosterone replacement therapy among some men did not appear to have an impact on the increase in fat mass.

The steady increase in fat mass is consistent with reports from other studies.

Factors associated with increased fat mass included the following:

• women – being female increased the chances of gaining fat mass
• men and women – use of TDF and integrase inhibitors, little or no exercise, and having a CD4+ count that fell below the 200 cell/mm³ mark at some point in the past

Bear in mind

1. The Italian study was observational in design. Such studies can find associations between the use of a certain drug or classes of drugs and, in this case, changes in body composition. However, due to built-in limitations, observational studies can never prove what scientists call “cause and effect.” In this case, an observational study cannot prove that exposure to TDF and/or integrase inhibitors caused an increase in fat mass.

2. The reasons underpinning the use of TDF and/or integrase inhibitors were not clear. As these reasons are unknown, the choice of which people used which regimen was not random. Thus, there could have been unmeasured factors that caused some people to use certain drugs or classes of drugs. These unmeasured factors could have introduced inadvertent bias when scientists drew their conclusions about TDF and integrase inhibitors. Therefore, we urge readers to treat the conclusions drawn about those drugs in this study with much caution. Other reports in this issue of TreatmentUpdate will deal with the issue of anti-HIV drugs and weight gain.

3. Many medicines unrelated to HIV treatment can cause weight gain (usually fat). None of these were taken into account when analysing the data. This omission is another potential confounding issue. More about such medicines will be reported later in this issue of TreatmentUpdate.

4. The Italian study did have strengths—it monitored people over time and it included large numbers of women. Another strength is that it used objective measures of body composition: DEXA scans done at one clinical centre. Also, the Italian study monitored participants longer than is usually done in studies of body composition and HIV infection. Therefore, the overall findings from the Italian study—sustained decrease in muscle and increase in fat—are likely occurring to some degree in other populations of HIV-positive people.

5. The importance of the present study is that it sounds an alarm. Similar to HIV-negative people who are aging, a large (2,600-person) group of HIV-positive people is showing troubling trends of muscle loss and fat gain, but these seem to be occurring at a younger-than-expected age range. If these changes in body composition are sustained, there may be problems ahead.

Addressing aging

If the full life-extending benefits of ART are to be realized, attention needs to be paid to what are commonly thought of as conditions of aging. This means that patients under the guidance of their healthcare providers have to engage in the hard work of maintaining a healthy life. This hard work will likely result in better quality of life as the onset of aging-related conditions (cardiovascular disease, pre-diabetes, diabetes, frailty, etc.) are delayed and their consequences minimized. Although some factors associated with trends in the present study were ones that participants likely had little control over, such as a history of low CD4+ cell counts, some issues they could control. For instance, about 40% of participants smoked and about 60% did not exercise regularly. These two issues can have a tremendous impact on overall health, mood, quality of life, and risk for stroke, heart attack and cancer, and so on. The results of the present study are a call to action.

—Sean R. Hosein

REFERENCES:

1. Debroy P, Sim M, Erlandson KM, et al. Progressive increases in fat mass occur in adults living with HIV on antiretroviral therapy, but patterns differ by sex and anatomic depot. Journal of Antimicrobial Chemotherapy. 2019 Apr 1;74(4):1028-1034.
2. Debroy P, Lake JE, Sim M, et al. Lean mass declines consistently over 10 years in people living with HIV on antiretroviral therapy, with patterns differing by sex. Antiviral Therapy. 2019;24(5):383-387.