Weight Gain Exacerbates Inflammation in People Living with HIV
Two studies are revealing the impact that weight gain and abdominal obesity may have on the health of people with HIV. Weight gain or mid-section obesity—even for people successfully treating HIV with antiretrovirals and with controlled viral loads—appears to not only heighten inflammation but is also linked to neurocognitive impairment.
Kristine Erlandson, MD, assistant professor at the University Colorado, Denver, presented data at the February 2015 Conference on Retroviruses and Opportunistic Infections from the Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS) trial. Her team documented changes in body mass index and inflammatory markers among 246 PEARLS participants that occurred during the 48-week study.
Over time, people in the study gained weight. The proportion of participants classified as either overweight or obese increased from 27% to 37%, while the proportion of “normal” weight participants decreased from 65% to 60% and “underweight” from 8% to 3%.
The researchers demonstrated that along with this weight gain came an increase in soluble CD14. Elevated soluble CD14 is a marker of immune activation and is associated with increased risk of mortality during HIV treatment. Incremental gains in body mass index were associated with increases in soluble CD14.
“The ‘return to health’ weight gain may be beneficial in the sickest individuals. Further weight gain among those that are overweight or obese may have detrimental effects,” Erlandson explained.
And this heightened inflammation and immune activation seen with weight gain appeared to happen even when viral loads were controlled—since the association held true even as the participants were treated with antiretroviral therapy and the researchers adjusted for baseline HIV viral load.
A second study by Fred Sattler, MD, and colleagues published in JAIDS in March, reports that the inflammation and immune activation tied to weight gain and abdominal obesity may cause further problems in the form of neurocognitive impairment.
This team of researchers hypothesized that when fat cells begin to store excess fat, white blood cells enter the fat tissue and secrete inflammatory proteins. These proteins, such as IL-6, then enter the body’s circulation and increase inflammation and immune activation—on top of the inflammation caused by HIV that already exists even when HIV is well-controlled.
In a sample of 152 participants participating in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study, the researchers assessed neurocognitive function and measured waist circumference as a measure of abdominal obesity. Participants had been on ART for an average of 15 years with 82% achieving undetectable viral loads.
Participants with abdominal obesity had significantly greater neuropsychological impairment than participants who weren’t abdominally obese—a finding that these researchers have previously reported. Interestingly, this association was tied to levels of IL-6, a marker of systemic inflammation. High levels of IL-6 led to a tighter association between waist circumference and neurocognitive impairment. In people with lower levels of the biomarker, this association wasn’t as strong.
In addition, waist circumference and IL-6 were most strongly associated with neurocognitive impairment in people with the highest levels of cerebrospinal fluid soluble CD40L, another marker of inflammation. The researchers speculate that being able to determine the source of soluble CD40L “will be important in unraveling the mechanism linking obesity and NCI [neurocognitive impairment] in HIV+ and possibly HIV- populations.”
The researchers present the idea that reducing abdominal obesity may be vital to reducing inflammation and neurocognitive impairment sometimes seen in people living with HIV. They suggested lifestyle changes such as healthier diet and exercise, but said there might be inflammation and neurocognition benefits in other options such as hormone-releasing agents that reduce abdominal fat and other anti-inflammatory drugs.
Erlandson, K. M. and others. Obesity and inflammation in resource-diverse settings of ART initiation. Abstract 778. CROI 2015.
Sattler, F. R. and others. Abdominal obesity contributes to neurocognitive impairment in HIV-infected patients with increased inflammation and immune activation. JAIDS. 2015.