In people with HIV, over-the-counter heartburn drugs may cause immune activation and inflammation
Long-term, regular use of proton pump inhibitor (PPI) acid blocking medications, like Prilosec, Prevacid, Nexium, Protonix and others, may increase immune activation and inflammation in people living with HIV, new research suggests. Immune activation, or inflammation, is important to monitor in people living with HIV because it is associated with things like cancer, heart disease and increased risk of mortality. The study’s primary researcher says there is not enough evidence from this study to recommend stopping the use of proton pump inhibitors, especially if used to treat ulcer diseases.
What is inflammation, and why does it affect people living with HIV? Read an explanation from Dr. Joanna Eveland
The study, published in Clinical Infectious Diseases, found that people living with HIV on long-term proton pump inhibitor therapy had higher levels of microbial translocation (i.e., bacterial products from the gut leaking into the blood stream), increased immune activation and lower gains in CD4 counts over time.
“This is concerning,” said lead author Jose Serpa-Alvarez, MD, MS. “We need more studies to confirm the findings, but if this effect is real, people with HIV on long-term use of proton pump inhibitors are gaining fewer CD4 cells and perhaps could have an increased risk of mortality.”
The study included a total of 37 adults living with HIV who were on long-term PPI use, 40 people living with HIV who were not taking PPIs, and 20 HIV-negative individuals who were not taking PPIs. All people living with HIV in the study had suppressed viral loads.
The researchers drew blood from participants and looked for the presence of proteins that indicate inflammation and microbial translocation. The researchers also compared changes in CD4 counts over time.
People living with HIV on long-term PPIs had significantly higher levels of immune activation markers compared to people living with HIV who were not taking acid reducers. People living with HIV on PPIs had an average sCD14 (a marker of inflammation) of 2.15 mcg/mL compared to 1.5 mcg/mL in people living with HIV not taking PPIs.
People with HIV on long-term PPIs also had significantly higher levels of LBP (21.78 mcg/mL) compared to people not taking PPIs (18.28 mcg/mL). LBP is a protein that is used to measure microbial translocation: People with higher levels of LBP have more bacterial products leaking from their gut into their blood stream than people with lower levels of LBP.
Microbial translocation is a normal process, explained Serpa-Alvarez. Normally, small amounts of bacteria in the gut travel through the mucosa of the gut and get into the bloodstream. But PPI medications, probably due to a reduction in the amount of acid produced in the stomach, lead to higher levels of microbial translocation in the gut.
“If you inhibit or reduce the proportion of acid, you’re probably going to have more bacteria,” said Serpa-Alvarez.
The theory, said Serpa-Alvarez, is that the increased amounts of bacterial products from the gut getting into the bloodstream leads to increased inflammation in people living with HIV.
“This is the result of the body trying to control these microbial products from the gut,” he said.
An unexpected finding from the study was that people living with HIV on long-term PPIs had lower average CD4 gains over a year than people living with HIV who were not taking PPIs. On average, the number of CD4 cells decreased in people living with HIV taking PPIs by 18 cells/mm3 over a year. In contrast, the average number of CD4 cells increased by 54 cells/mm3 in people living with HIV not taking PPIs.
This finding on CD4 counts, said Serpa-Alvarez, was an observation that needs to be confirmed with further testing.
What does this study mean for people living with HIV?
“There is not enough evidence from this study to recommend stopping these drugs [proton pump inhibitors],” said Serpa-Alvarez. “PPIs do a good job of treating peptic ulcer disease and other gastric ulcer diseases.”
“At the same time, I would recommend patients discuss this with their physicians if they are concerned. The most important thing is, re-evaluate the need for these medications. In other words, do you have an approved indication that requires you to be taking a proton pump inhibitor? Or not? Or maybe you did in the past, but you don’t anymore,” said Serpa-Alvarez.
Serpa, J.A. and colleagues. 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. Clinical Infectious Diseases, July 2017.