Long-Term PPI Use Discouraged for HIV-1-Infected Patients

Long-term PPI use may up microbial translocation
Long-term PPI use may up microbial translocation

NEW ORLEANS, LA—Long-term use of proton pump inhibitors (PPIs) might increase microbial translocation and innate immune activation but not enterocyte turnover or T-cell activation among people infected with HIV-1, according to research findings reported at IDWeek 2016.

Understanding the clinical implications of these findings will require larger studies be conducted; in the meantime, “cautious use of long-term PPIs is advised in this patient population,” noted Jose Serpa, MD, of the Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, in Houston, TX, and colleagues.

Gut damage can cause the movement or translocation of microbes to other organs, and can trigger systemic immune activation among people with HIV infection, increasing mortality risk. Because PPIs can foster overgrowth of gut microbial communities, the authors sought to determine whether long-term PPI use increases microbial translocation and thereby triggers systemic inflammation among patients with chronic HIV infection.

The study enrolled 20 HIV-negative volunteers as controls and 77 HIV-positive study participants taking antiretroviral therapy (ART): 37 HIV-infected patients with long-term PPI use (defined as having filled 6 or more 30-day prescriptions for PPIs in the past year), and 40 HIV-positive study control participants.

“We determined the CD38+HLA-DR+ (activated) CD8+ T-cell frequency and plasma levels of lipopolysaccharide (LPS, a component of Gram-negative bacteria), LPS binding protein (LBP, induced by LPS), soluble CD14 (sCD14, reflecting LPS-induced monocyte activation), and intestinal fatty acid binding protein (I-FABP, reflecting enterocyte turnover),” they reported.

Control-group participants were younger on average (aged 55.4 vs. 60.5 years; P=0.03) and less likely to have hypertension (50% vs. 76%; P=0.02) or be taking statins (25% vs. 54%; P=0.01) than the HIV-positive study participants. However, at baseline, the nadir and CD4+ T-cell counts and time on ART was similar among study groups.

“Cases had higher concentrations of sCD14 (2.15 vs. 1.50mcg/mL; P<0.001) and LBP (21.78 vs. 18.28mcg/mL; P=0.013) than controls,” the researchers reported. “Higher sCD14 levels remained significantly associated with PPI use after adjustment for age, hypertension, and statin use in the multivariate model.”

The authors reported that “levels of activated CD8+ T-cells, LPS, and I-FABP were similar between cases and controls. HIV-infected cases and controls had higher levels of inflammation and microbial translocation markers than HIV-uninfected volunteers.”

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