“HIV greatly affects the gut, even early after infection, causing the gut to lose a large portion of its CD4 cells and its normal barrier function,” explains Allison Ross Eckard, MD. “These changes increase microbial translocation, which then cause systemic inflammation and immune system activation. This increases the risk of HIV-related comorbidities, like cardiovascular disease and diabetes. Thus, it’s important to study how to measure gut inflammation levels in patients with HIV at a given time, as well as how it may contribute to development of comorbidities and other HIV complications.”

Studies focused on Crohn’s disease indicate that levels of the biomarker fecal calprotectin are a good indicator of one’s gut inflammation at a given moment, with stool measurements correlating well with degree of disease seen on endoscopy or colonoscopy. With data lacking on the utility of the biomarker in patients with HIV, Dr. Eckard and colleagues conducted a cross-sectional study to determine if fecal calprotectin levels were elevated in patients with HIV and if ART affects those levels. Findings were published in the Journal of Acquired Immune Deficiency Syndrome.

Fecal Calprotectin & Gut Inflammation by HIV Status

For the study, patients with HIV—some treated with ART and some ART-naïve—and without HIV underwent a comprehensive clinical and laboratory assessment, including collection of stool samples. Fecal calprotectin was measured by enzyme-linked immunosorbent assay ELISA. The researchers also measured plasma biomarkers of inflammation.

“We determined that fecal calprotectin levels were significantly higher in individuals with HIV compared with people without HIV,” Dr. Eckard says. “Fecal calprotectin levels were the highest among individuals with HIV who had not yet started ART (median, 144 µg/g). Once virologically suppressed with antiretrovirals, fecal calprotectin levels decreased, albeit not significantly (median, 78 µg/g). And both HIV groups had significantly higher levels than individuals without HIV (median, 41 µg/g). In addition, more than one-half of the ART-naïve individuals had very high fecal calprotectin levels (>100 µg/g), demonstrating how HIV causes a significant amount of gut inflammation, especially when untreated.”

The study team also showed that fecal calprotectin levels were correlated with systemic markers of inflammation and immune activation (Table), suggesting that fecal calprotectin—which can be reliably and easily measured—may be a useful marker to measure gut inflammation in patients with HIV over time and may be helpful in determining how gut inflammation contributes to systemic inflammation and immune activation in patients with HIV, according to Dr. Eckard. Indeed, among those with HIV, fecal calprotectin concentrations were positively associated with high-sensitivity C-reactive protein, soluble tumor necrosis factor receptor (sTNFR)-II, and soluble vascular cellular adhesion molecule, while being inversely associated with CD4 cell counts. When compared with uninfected controls, ART-treated patients with HIV had significantly higher levels of all inflammatory markers, and ART-naïve patients with HIV had significantly higher levels of all but D-dimer and sTNFR-I—but with a trend toward significance for sTNFR-I.

HIV’s Impact on the Gut

“Our study highlights the degree to which HIV affects the gut,” notes Dr. Eckard. “Many individuals in our study had fecal calprotectin levels in the Crohn’s disease range. Our findings also suggest that fecal calprotectin may be a useful biomarker for measuring gut inflammation in HIV, similar to its utility in Crohn’s disease.”

With the knowledge that HIV’s dramatic effects on the gut, in turn, affect many other organ systems and have implications for comorbidity development, Dr. Eckard notes the need for future studies to determine how to improve HIV-related gut inflammation and gut integrity issues, “which could have profound effects in other aspects of HIV-related immune dysfunction, comorbidity development, and mortality.”