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HomeHIV/AIDSPeople with HIV must use PPIs cautiously

People with HIV must use PPIs cautiously

Proton pump inhibitors should be used with caution in people with HIV, researchers from the Baylor College of Medicine and the University of Texas Medical Branch at Galveston say, after finding that people who received long-term treatment for gastric reflux with the drugs failed to gain CD4 cells and experienced more immune activation.

Proton pump inhibitors (PPIs) such as lansoprazole, pantoprazole and omeprazole are frequently prescribed to manage gastric reflux by suppressing stomach acid production. Gastric reflux is a common condition that is caused by hiatus hernia or by stress, smoking, coffee, alcohol, fatty or acidic foods, eating too close to bedtime, and by obesity or pregnancy. Gastric reflux is also a side-effect of some HIV medications, as well as drugs used to treat hypertension.

Although PPIs are considered safe for long-term use, there is some evidence that the drugs promote bacterial overgrowth in the large intestine. PPI treatment is associated with an increased risk of gastrointestinal infections such as salmonella and campylobacter, two of the most frequent causes of food poisoning.

Gut bacterial overgrowth may be a particular problem in people living with HIV because bacteria from the gut can cross an intestinal wall that is damaged as a result of HIV infection, and cause immune activation.

The strength of immune activation predicts the progression of HIV disease in untreated people. In people on antiretroviral treatment, immune activation is still detectable and is associated with lower CD4 cell counts. There is some evidence that immune activation also contributes to the development of cardiovascular disease in people living with HIV.

To study the impact of PPIs on immune activation and CD4 cell counts, researchers from the University of Texas recruited 77 people living with HIV who had been receiving antiretroviral treatment for at least 18 months and who had an undetectable viral load for at least 12 months before joining the study.

The study population consisted of 37 people who had taken PPIs for at least six months out of the previous 12 and 40 people who did not use PPIs. The study excluded people who had received antibiotic treatment in the previous month.

All participants were male, recruited through the Veterans Affairs Medical Centre. PPI users were older (59 years vs 54 years) and more likely to be taking statins or hypertension medication but were otherwise well matched. The study population was 48% African-American, 35% men who have sex with men, 32% heterosexual and 19% had hepatitis C. The median CD4 cell count at study enrolment was 626 cells/mm3 (609 cells/mm3 in the PPI group and 641 cells/mm3 in the non-PPI group). Just under half were taking protease inhibitor-based treatment (44%), while 55% were taking a non-nucleoside reverse transcriptase inhibitor. Participants had been on treatment for a median of 12 years.

PPI users had been taking the drugs for a median of 3.7 years prior to enrolment.

The researchers measured two markers of immune activation – soluble CD14 and activated CD8+-CD38+HLA-DR T-cells – and found that sCD14 was significantly higher in people taking PPIs (P < 0.01). One marker of microbial translocation, LBP, was elevated in this group, while another marker of intestinal repair was reduced in the PPI group.

After controlling for age, hypertension and statin use, a multivariate analysis showed that PPI use was significantly associated with higher levels of sCD14 as a marker of immune activation.

People taking PPIs also experienced a median CD4 cell decline of 18 cells in the year preceding enrolment in the study, whereas people not taking PPIs gained a median of 54 cells/mm3, and this difference was statistically significant (p = 0.03). The study authors say that immune activation is the most likely cause, and that “cautious use of PPIs is advised in this population” until more studies can be done to look at long-term effects in larger populations.

In particular, studies are needed in women as well as men, and must examine whether long-term PPI use results in poorer CD4 cell recovery after starting treatment and if higher immune activation in PPI users has any harmful clinical consequences.

Abstract
Background: Translocation of microbial products from the damaged gut causes increased immune activation in 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 <0.01), and LBP (21.78 vs. 18.28 mcg/mL, P=0.02), but lower I-FABP levels (608.5 vs. 2281.7 pg/mL, P=0.05) 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 = 0.03). 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.

Authors
JA Serpa, AM Rueda, A Somasunderam, NS Utay, D Lewis, JP Couturier, KG Breaux, M Rodriguez-Barradas

[link url="http://www.aidsmap.com/Proton-pump-inhibitors-may-blunt-CD4-cell-gains-cause-immune-activation-in-people-with-HIV/page/3155517"]Aidsmap material[/link]
[link url="https://academic.oup.com/cid/article-abstract/doi/10.1093/cid/cix609/3933542/Long-term-use-of-proton-pump-inhibitors-is"]Clinical Infectious Diseases abstract[/link]

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