Fat Gains Continue and Lean Mass Falls in Group on Long-Term HIV Therapy
People with HIV gained more lean body mass and fat in the first 96 weeks of antiretroviral therapy than did HIV-negative people over the same length of time.1 But after 96 weeks, through another 5 years of observation, the HIV group lost lean mass compared with the HIV-negative group and continued to gain more fat. U.S. researchers who conducted the study warned that long-term lean mass loss and fat gains could promote obesity-related diseases (like diabetes) and harm physical function in people with HIV.
Body composition, including fat and lean mass, has an important impact on overall health. People with long-term diseases like AIDS often lose both fat and lean mass (which includes muscle). When HIV-positive people first start antiretroviral therapy, they usually gain both fat and lean mass as their health improves. But few studies have explored changes in body composition for several years after people start antiretrovirals. And no studies have compared long-term body composition changes in people with and without HIV. Understanding how fat and lean mass change over time in people with HIV is important because such changes can have direct effects of health.
Researchers working with the U.S. AIDS Clinical Trials Group (ACTG) conducted this study to learn more about multi-year body composition changes in HIV-positive people taking antiretroviral therapy. They compared those changes with an HIV-negative group around the same age.
How the Study Worked
This analysis involved HIV-positive adults who participated in an ACTG trial that compared diverse first-line antiretroviral combinations.2 Some people in that trial agreed to have whole-body DXA scans, a simple imaging study that measures body composition, including fat and lean mass. These 269 people had a DXA scan when they entered the study and another scan 96 weeks later.3
For the new analysis,1 ACTG researchers attempted to contact all of these 269 people and invited them to have another DXA scan. This final DXA scan was done about 5 years after the 96-week scan. The ACTG team compared findings in the three scans -- the one done when people entered the original trial, the one done after 96 weeks of treatment in the original trial, and the one done about 5 years after that for the new analysis.
The researchers created an HIV-negative comparison group from two long-term studies of men and women who had whole-body DXA scans done over the course of several years. These HIV-negative men and women were in the same age range as HIV-positive people when the HIV group had their first DXA scan: 20 to 64 years for men and 23 to 55 years for women.
The ACTG team used standard statistical methods to compare rates of body composition change (lean mass, total fat, trunk fat, limb fat) in HIV-positive and HIV-negative people during the first 96 weeks of follow-up and in the multi-year period after the first 96 weeks. This type of analysis accounts for the impact of several factors on body composition: age, male versus female sex, physical activity level, cigarette smoking, and alcohol use. As a result, the analysis provides a good estimate of how treated HIV infection alone affects body composition over time. In people with HIV, the researchers conducted further analyses to identify factors that independently affect rates of body composition change.
What the Study Found
This analysis focused on 97 people with HIV and 614 HIV-negative people. Median (midpoint) age was younger in the HIV group than in the HIV-negative group (40 versus 46 years), and the HIV group had a longer time between their first and final DXA scan (7.6 versus 6.9 years). Most people in both groups, about 87%, were men. At the time of the final DXA scan, 86% of HIV-positive people had a viral load below 200 copies, and their median CD4 count stood at 598.
Compared with HIV-negative people, those with HIV had a lower body mass index (a measure of weight) at the time for the first DXA scan (24 versus 28 kilograms per height in meters squared) and at the time of the final DXA scan (27 versus 29 kg/m2).
During the first 96 weeks of observation (between the first and second DXA scans), people with HIV gained significantly more lean mass than people without HIV (average 0.53 versus 0.06 kilogram per year) (Figure 1). In this comparison and the following comparisons, "significant" means statistical tests show that the difference between groups does not result from chance. During this 96-week period, the HIV group also gained significantly more total fat than the HIV-negative group (1.43 versus 0.15 kilogram per year), more trunk fat (0.69 versus 0.07 kilogram per year), and more limb fat (0.70 versus 0.08 kilogram per year).
About 5 years passed between the second the third DXA scans in the two study groups. During this period, the HIV group lost lean mass while the HIV-negative group continued to gain lean mass (average -0.28 versus +0.06 kilogram per year) (Figure 2). This difference and the following differences in fat changes were significant, meaning statistical analysis shows they did not result from chance.
Compared with the HIV-negative group, people with HIV gained significantly more total fat in the 5 years between the second and third DXA scans (average 0.70 versus 0.15 kilogram per year). In this 5-year period, people with HIV also gained significantly more trunk fat than the HIV-negative group (average 0.38 versus 0.07 kilogram per year) and more limb fat (0.28 versus 0.08 kilogram per year).
Statistical analysis identified a single factor linked to greater gains in lean mass, total fat, trunk fat, and limb fat in the 96 weeks between the first and second DXA scans in people with HIV: A lower pretreatment CD4 count meant a greater gain in lean mass and the three fat measures -- regardless of whatever other factors might be affecting lean mass and fat gains. A similar analysis showed that older age and black race favored loss of lean mass in the 5 years between the second and third DXA scans. During that same period, older age and female sex favored smaller gains in total fat, trunk fat, and limb fat.
What the Results Mean for You
This long study comparing antiretroviral-treated HIV-positive people with HIV-negative people made several important findings: First, it confirmed earlier research showing that HIV-positive people gain both lean mass and fat in the first 2 years of antiretroviral therapy -- and they gain more lean mass and fat than HIV-negative people. For people low in fat and lean mass because of HIV infection, those gains are a sign of returning health with antiretroviral therapy.
But the second major finding of this study raises concerns: Compared with HIV-negative people, HIV-positive people continued to gain fat over the next 5 years of follow-up, while they lost lean mass. High fat and low lean mass can threaten good health. For example, the researchers suggest that those fat and lean mass changes could explain higher rates of frailty in people with HIV versus without HIV.4,5 High weight is a well-known risk (Figure 2). From week 96 of antiretroviral therapy through the following 5 or more years, people with HIV lost lean mass and gained more fat (in kilograms per year) than HIV-negative people not taking antiretrovirals. factor for diabetes, as shown in the next study reviewed in this issue of HIV Treatment Alerts.6
This study does not explain why HIV-positive people taking antiretrovirals for many years lose lean mass and gain fat. The analysis showed that these changes could not be explained by the type of antiretrovirals people were taking or by smoking, alcohol use, or lack of physical activity. The statistical analysis did link older age and black race to lean mass loss. This does not mean older age and black race cause lean mass to decrease, but it does suggest older people and blacks run a higher risk of this drop.
The findings underline the importance of maintaining lean mass (including muscle) and avoiding too much weight gain during the many years people can expect to take antiretroviral therapy. The HIV group in this study started antiretroviral therapy with a normal median body mass index of 24. Seven years later, the group had a median body mass index of 27, which is in the overweight range. (Normal body mass index runs from 18.5 to 24.9, overweight from 25 to 29.9, and obesity from 30 on up. You can find a body mass index calculator at reference 7 below.)
If you are losing muscle or gaining too much weight, talk to your HIV provider. Your provider can refer you to a nutritionist for dietary advice or to an exercise planner to help you gain or maintain lean mass.
- Grant PM, Kitch D, McComsey GA, et al. Long-term body composition changes in antiretroviral-treated HIV-infected individuals. AIDS. 2016;30:2805-2813.
- Sax PE, Tierney C, Collier AC, et al. Abacavir/lamivudine versus tenofovir DF/emtricitabine as part of combination regimens for initial treatment of HIV: final results. J Infect Dis. 2011;204:1191-1201.
- McComsey GA, Kitch D, Sax PE, et al. Peripheral and central fat changes in subjects randomized to abacavir-lamivudine or tenofovir-emtricitabine with atazanavir-ritonavir or efavirenz: ACTG Study A5224s. Clin Infect Dis. 2011;53:185-196.
- Kooij KW, Wit FW, Schouten J, et al. HIV infection is independently associated with frailty in middle-aged HIV type 1-infected individuals compared with similar but uninfected controls. AIDS. 2016;30:241-250.
- Desquilbet L, Jacobson LP, Fried LP, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci. 2007;62:1279-1286.
- Herrin M, Tate JP, Akgün KM, et al. Weight gain and incident diabetes among HIV-infected veterans initiating antiretroviral therapy compared with uninfected individuals. J Acquir Immune Defic Syndr. 2016;73:228-236.
- National Heart, Lung, and Blood Institute. Calculate your body mass index.