Gut Barrier Dysfunction Markers Predict Abdominal Fat Increases in ART-Naive Individuals

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Abdominal fat gains due to antiretroviral therapy may be predicted by gut barrier dysfunction markers in ART-naive individuals.
Abdominal fat gains due to antiretroviral therapy may be predicted by gut barrier dysfunction markers in ART-naive individuals.

It is unclear to what extent antiretroviral therapy affects gut barrier function, according to a study recently published in Clinical Infectious Diseases. However, abdominal fat gains due to antiretroviral therapy may be predicted by gut barrier dysfunction markers in individuals who have never undergone therapy.

This study included 231 participants with HIV who had never undergone antiretroviral therapy, 90% of whom were male and 48% of whom were white non-Hispanic. These individuals were randomly assigned to receive darunavir/ritonavir, atazanavir/ritonavir plus tenofovir disoproxil fumarate/emtricitabine, or raltegravir during a 96-week treatment period.

Intestinal fatty acid binding proteins increased by a factor of 1.7 during the 96-week period and showed no significant difference between arms (P <.2). Raltegravir was associated with increased levels of the gut integrity marker zonulin relative to regimens based on protease-inhibitors (P =.02), whereas changes in lipopolysaccharide-binding protein and ileal bile acid-binding proteins were not significant. Zonulin levels showed a 1.06-fold gain by week 4, and changes were sustained at weeks 24 and 96.

Individuals with higher levels of intestinal fatty acid binding proteins at baseline showed increased body mass index (2.5%) and visceral (16%) and total (9%) adipose tissue (P <.04) by the end of the 96-week period.

Participants in this study had a median age of 36 years, CD4 counts of 338 cells/µL, and HIV-1 RNA 4.56 log10 copies/mL. The study researchers investigated changes between groups using Wilcoxon rank-sum tests and evaluated correlations between gut markers, body mass index, adipose tissues, and insulin resistance using linear regression models.

To analyze non-normal biomarkers, figures were transformed to the log10 scale. Each treatment group's gut integrity markers were analyzed throughout the 96-week study period, with mean fold-changes calculated by converting to log scale and then transforming again to linear scale.

The study researchers concluded, "[while antiretroviral therapy] induces changes in soluble markers of gut barrier dysfunction (with subtle differences between regimens), the extent to which they improve or worsen gut barrier function remains unclear. Nevertheless, markers of gut barrier dysfunction in [antiretroviral therapy]-naive individuals predict increases in total and visceral abdominal fat with treatment initiation."

Reference

El Kamari V, Moser C, Hileman CO, et al. Lower pretreatment gut integrity is independently associated with fat gain on antiretroviral therapy [published online August 23, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy716

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