NIH Awards $7.8 Million for Antibiotic Study of Patients With Emphysema, HIV

The National Institutes of Health’s National Heart, Lung, and Blood Institute has awarded Weill Cornell Medicine in New York, New York, a 5-year $7.8 million grant to study whether antibiotic doxycycline slows the progression of emphysema with well-controlled HIV.

“There are no available treatments for addressing emphysema progression. Inhalers commonly prescribed to patients with the disease only alleviate airway symptoms,” said Robert Kaner, MD, an associate professor of genetic and clinical medicine at Weill Cornell Medicine, in a statement. “If doxycycline can slow the lung damage caused by emphysema, it would be a landmark finding.”

The institute awarded the grant based on the results of a previous study by Kaner approximately 15 years ago, which showed that lung fluid samples from individuals with HIV and early emphysema had increased levels of enzymes called matrix metalloproteinases (MMPs), which are known for breaking down healthy tissue. Investigators demonstrated that HIV could bind its airway cells and reprogram them to release MMP.

Doxycycline is approved as an oral antibiotic used to treat bacterial infection and prevent tissue breakdown for conditions that include severe acne and gum disease. For gum disease, doxycycline acts as an MMP inhibitor. Investigators conducted a pilot study among 27 individuals with HIV and chronic obstructive pulmonary disease (COPD) or emphysema, with a history of smoking. They aimed to confirm that doxycycline, given twice daily, over 24 weeks was safe and well-tolerated. They found that there was a trend toward reduced MMP-9 levels in lung fluid compared with treatment with a placebo.

“Smoking rates are at least double among people living with HIV, about 30[%] to 40[%] compared to 13[%] for individuals who are HIV-negative,” Marshall Glesby, PhD, MD, associate chief of the Division of Infectious Diseases at Weill Cornell Medicine, said in the statement. “However, even after adjusting for smoking status, emphysema is more severe and progresses faster in individuals with HIV than in those who are HIV-negative.”

The grant will fund a phase 2 clinical trial of doxycycline in a large group of individuals with emphysema and HIV who smoke or used to smoke. Investigators aimed to recruit 250 individuals at 18 collaborating sites across the United States. Individuals in the study will receive either doxycycline or a placebo twice daily for 72 weeks.

Investigators will study whether doxycycline can effectively slow emphysema progression. They will analyze test results that show the surface area of the lung, which will be available for gas exchange, high-resolution computed tomography scans, and patient-reported outcomes on breathing ability, as well as quality of life. Clinical trial sites will be selected for their expertise in pulmonology and infectious diseases, Glesby explained.

“If doxycycline can successfully slow emphysema progression in patients with HIV, future research could also explore whether it or other MMP inhibitors would work well in patients without HIV,” Kaner said in the statement. “Deciding what to do next will be an excellent problem to have.”

Reference

NIH grant funds antibiotic trial for patients with HIV and emphysema. EurekAlert. News release. December 15, 2022. Accessed December 21, 2022. https://www.eurekalert.org/news-releases/974584