Long-term Use of Proton Pump Inhibitors Is Associated With Increased Microbial Product Translocation, Innate Immune Activation, and Reduced Immunologic Recovery in Patients With Chronic Human Immunodeficiency Virus-1 Infection.

BACKGROUND: Translocation of microbial products from the damaged gut causes increased immune activation in human immunodeficiency virus (HIV). Proton pump inhibitors (PPIs) predispose to bacterial overgrowth in the gut. We hypothesized that long-term use of PPIs is associated with greater microbial translocation and immune activation in HIV. METHODS: HIV-infected persons on suppressive antiretroviral therapy (ART), including those receiving long-term PPIs (PPI+ group) or not (PPI- group), were enrolled. We determined CD38+HLA-DR+CD8+ (activated) T-cell frequency, and plasma levels of lipopolysaccharide (LPS), LPS binding protein (LBP), soluble CD14 (sCD14), and intestinal fatty acid binding protein (I-FABP). RESULTS: We recruited 77 HIV-infected participants (37 PPI+ and 40 PPI-) and 20 HIV-uninfected volunteers. PPI+ subjects were older and more likely to have hypertension and receive statins than PPI-. Nadir and enrollment CD4 counts, activated T-cells, and time on ART were similar in both groups. PPI+ group had higher sCD14 (2.15 vs. 1.50 mcg/mL, P < .01), and LBP (21.78 vs. 18.28 mcg/mL, P = .02) but lower I-FABP levels (608.5 vs. 2281.7 pg/mL, P = .05) than PPI-. In multivariate analysis, sCD14 levels remained associated with PPIs. In the year prior to enrollment, PPI+ group lost more CD4 cells than PPI- (-18 vs. 54 cells/mm3, P = .03). HIV-infected subjects had higher immune activation and microbial translocation biomarkers than uninfected volunteers. CONCLUSION: In HIV, long-term use of PPIs was associated with increased microbial translocation, innate immune activation, and reduced immune reconstitution. Further studies are needed to evaluate the clinical implications of our findings. In the meantime, cautious use of PPIs is advised.

Neglected infections of poverty in Texas and the rest of the United States: management and treatment options.

In the poorest regions of the United States, especially along the Gulf Coast and in South Texas, are a group of endemic parasitic and related infections known as the neglected infections of poverty. Such infections are characterized by their chronicity, disabling features, and disproportionate impact on the estimated 46 million people who live below the U.S. poverty line. Today more Americans live in poverty than ever before in the half-century that the Census Bureau has been recording poverty rates. In association with that poverty, a group of major neglected infections of poverty have emerged in the United States. Here we describe the major neglected infections of poverty in the United States, with a brief overview of their significant epidemiological features, their links with poverty, and our approaches to their diagnosis, management, and treatment.