RATIONALE: Emphysema is prevalent in smoke-exposed people living with HIV. Matrix metalloproteinases are increased in bronchoalveolar lavage (BAL) fluid in People Living with HIV (PLWH) with emphysema. Doxycycline is an FDA-approved MMP-9 inhibitor, in addition to its antimicrobial properties.

OBJECTIVES: To test the safety and tolerability of doxycycline in PLWH.

METHODS: Single center double blind randomized placebo-controlled (2:1) pilot study of doxycycline 100 mg po twice daily in 27 PLWH who have COPD and/or emphysema (NCT01744093).

MEASUREMENTS AND MAIN RESULTS: Doxycycline was safe and well-tolerated. There were robust serum and BAL fluid levels of doxycycline in individuals assigned to the doxycycline arm. Preliminary evidence of potential biologic effects of doxycycline in the lung included a reduction in BAL lung lymphocytes and a trend toward decreased MMP-9 activity.

CONCLUSION: These data provide a rationale for a Phase II 72-week randomized placebo-controlled trial of doxycycline to slow the progression of emphysema in PLWH (NCT05382208).