Effort on to Tackle Emphysema in People Living With HIV

The National Heart, Lung, and Blood Institute awarded a five-year, $7.8 million grant to Weill Cornell Medicine to study whether the antibiotic doxycycline may slow progression of emphysema in HIV-positive patients.

Emphysema is a type of chronic obstructive pulmonary disease that damages the walls of the air sacs in lungs and reduces the available surface area for gas, thus making it harder to breathe. With smoking the biggest risk factor for the disease, nearly 30 percent of HIV-positive people develop the disease in their lifetime.

“Smoking rates are at least double among people living with HIV, about 30 to 40 percent compared to 13 percent for individuals who are HIV-negative,” said co-principal investigator Dr. Marshall Glesby in a statement on Weill Cornell Medicine.

The grant was awarded due to findings from Dr. Robert Kaner and colleagues from nearly 15 years ago. They discovered lung fluid from HIV-positive patients and early emphysema had increased enzymes called matrix metalloproteinases (MMPs), known for breaking down healthy tissue. The research also showed HIV could bind to airway cells and reprogram them to release MMP.

Doxycycline, an approved, oral antibiotic typically used for conditions like gum disease and severe acne, can also act as an MMP inhibitor. In the phase 1 trial, Drs. Kaner and Glesby observed 27 individuals with HIV, COPD, and a history of smoking as they took doxycycline twice daily over 24 weeks. The results showed the antibiotic to be safe and well-tolerated, with a trend toward reduced MMP-9 levels in comparison to other treatments.

The upcoming phase 2 clinical trial aims to recruit 250 participants at 18 collaborating sites across the US for the 72-week study to determine doxycycline’s effectiveness at slowing emphysema progression.

“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,” said Dr. Kaner. “Deciding what to do next will be an excellent problem to have.”