Fat Gains After Starting HIV Treatment Associated With High Viral Loads
March 17, 2015
Lean Body Mass
There were significant increases in lean body mass as well, of 1.2% to 2%, with a trend toward greater gains in lean mass on atazanavir/ritonavir. BMI increased in all the arms by about 3%, but there was no significant difference between arms. There was also no change in VAT to total adipose tissue ratio in either arm or between the arms.
The changes in central fat correlated well with changes in peripheral fat, and all these fat changes correlated well with the lean body mass changes, as well.
Baseline Associations With Changes in Body Composition
People who started in the high viral load strata gained two or three times the amount of fat than people who started in the lower viral load strata.
The researchers also looked into the association of parameters at baseline with the changes in body composition. Most strikingly, for both SAT and VAT, they found that the people who started in the high viral load strata gained two or three times the amount of fat than people who started in the lower viral load strata, regardless of the treatment regimen. It was notable though that both lower baseline leptin and higher adiponectin were also associated with greater gains in fat.
Demographics, baseline BMI, CD4 or inflammatory markers were not associated with increases in VAT, though higher IL-6 levels at baseline were associated with greater SAT gains in the study.
In contrast, increases in lean body mass were associated with higher IL-6 and D-dimer as well as lower CD4 count and higher HIV viral load at baseline.
"A 30% gain in fat after two years -- that's really bad. It is a short duration of treatment!" McComsey said, regarding the association of fat gain with high baseline viral loads. She stressed the need for more research to determine the cause of lipohypertrophy in people living with HIV.
Other studies presented at CROI 2015, in a thematic discussion titled "Fat Without Borders," also addressed the topic. The SECOND-LINE RCT DXA sub-study found that limb fat gain isn't limited to first-line regimens -- it was observed in both boosted-protease-inhibitor-based and raltegravir-based regimens. Again, there was no significant difference in regimens (including no difference between the regimens that spared or contained nucleoside analogues). This trial, which was conducted in Argentina, India, Malaysia, South Africa and Thailand, did find more demographic differences -- with more limb fat loss in African participants than among Asian participants, and with women being more likely to gain limb fat.
A second study by Kristine M. Erlandson et al, which looked at fat gain after treatment initiation in various countries, found that incremental increases in BMI to the point of being overweight or obese were associated with increases in markers of inflammation over time. Erlandson suggested that unhealthy weight gain could cause inflammation.
HIV replication does alter metabolism; it is possible that high viral replication makes the body think that it is starving.
Other factors may also lead to both the increase in inflammation and the increase in weight. One possibility is that the cause is similar to what appears to be causing cardiovascular disease -- chronic inflammation caused by both ongoing viral replication and by the microbial translocation (the leaking of gut flora into systemic circulation). Damage to the gut mucosa is a consequence of HIV infection, and having had a higher viral load could lead to more gut damage and more inflammation.
Another possibility is suggested by McComsey's other finding -- that both lower baseline leptin and higher adiponectin were also associated with greater gains in fat. Low leptin and high adiponectin levels are often found among stressed, starving individuals -- and alter the metabolism in ways that tell the body to store calories as fat. HIV replication does alter metabolism; it is quite possible that high viral replication makes the body think that it is starving -- and when antiretroviral therapy removes most of the HIV, it may be very difficult to reset that programming.
Theo Smart is an HIV activist and medical writer with more than 20 years of experience. You can follow him on Twitter @theosmart.
Copyright © 2015 Remedy Health Media, LLC. All rights reserved.
This article was provided by TheBodyPRO. It is a part of the publication The 22nd Conference on Retroviruses and Opportunistic Infections (CROI 2015).
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