Abdominal Body Fat Gains on ART and Viral Load: It Matters Where You Start
New research presented at CROI 2015 last week gave new insight about a puzzling aspect of antiretroviral therapy (ART): lipodystrophy, or changes in body fat distribution. New findings show that people with higher viral loads when starting ART for the first time are more likely to undergo substantial body composition changes, such as an increased amount of fat in the abdominal area (called “central adiposity”), than those who start treatment with a lower viral load (abstract 140). This finding presents another reason why it’s important to start HIV treatment early.
Though it’s unclear why people on ART get lipodystrophy, protease inhibitors have, in the past, been suspected of causing body fat changes. Grace McComsey, MD, from Case Western Reserve University, presented new evidence that HIV, viral load and inflammation may also play a role in body composition changes above and beyond that which may be caused by any specific drug regimen.
In her study, treatment-naïve people with HIV who had viral loads in the highest range (over 100,000 copies/mL) before starting treatment had greater gains in abdominal fat and peripheral fat (e.g., fat on arms and legs) than people starting treatment with lower viral loads. People with higher IL-6 (a marker of immune activation) before starting treatment also had greater gains in peripheral fat.
A total of 328 people with no prior ART experience took part in the randomized controlled study, and were followed for a total of 96 weeks. Most (90%) of the participants were men, and the median age of study participants was 36. They were assigned to take tenofovir/emtricitabine (Truvada) plus one of the following combinations: 1) the protease inhibitor atazanavir and ritonavir (Reyataz and Norvir); 2) the protease inhibitor darunavir and ritonavir (Prezista and Norvir); or 3) the integrase inhibitor raltegravir (Isentress).
The researchers hypothesized that different medications would have different effects on fat gain. That’s not what they saw, however.
Using a body composition X-ray scan called DEXA, the research team found that men across all three study groups gained limb fat over the course of the study—with no differences based on the medication participants in each group were taking. Average increases per group ranged between 11% and 20%. Men also increased their abdominal fat by an average of 16% to 29% during the study—again, with no significant differences between medication groups.
Body mass increased during the study, with gains in all three study groups ranging from 3% to 3.5%.
In a question and answer session after her talk, McComsey showed concern about their findings, saying, “A 30% gain in fat after two years—that’s really bad. That’s a relatively short duration of treatment.”
Because there were no differences that seemed to be associated with the type of ART regimen, the researchers looked back to see if any of the factors they measured at baseline might be related to their findings. That’s when they realized, according to to McComsey, that viral loads prior to starting ART had an effect on later fat gain.
“Regardless of the treatment regimen, people who started at the high viral load strata gained double or triple the amount of fat than people who started at the lower viral load strata,” explained McComsey. Their findings provide another reason why it’s important to start HIV medications soon after diagnosis, and not wait until viral loads are elevated or CD4 counts are low.
The fat gains seen in the study may not necessarily be a negative consequence for people with high viral loads when they begin ART. McComsey said that the people in their study with higher viral loads prior to initiating ART, “may be sicker, in a way,” than people with lower viral loads, and that a greater gain in fat seen during ART may mark a “return to health.”