Old drug, new hope: doxycycline tested for HIV-Related emphysema

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Male or female age 30 years and older at screening visit. * HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to the enrollment visit, and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. * Current or former smoker with at least a 3 pack-year history of cigarette smoking at screening visit. * Evidence of emphysema on high resolution CT (HRCT) of the chest done at pre-entry visit (Visit 2). Emphysema is defined as either: 1. Mild, moderate, or severe emphysema assessed by central reader(s) at the CT Imaging Core; or 2. Quantification of ≥ 5% of voxels with density \< -950 Hounsfield Units (HU) as quantified by the CT Imaging Core. All participants with emphysema by either or both criteria must have ≤ 35% of voxels with density \< -950 HU. * Screening and Entry DLCO measurements must be within 15% of each other. The PFT quality at both visits must be acceptable based on ATS Quality Criteria. 1. Screening (Visit 1) Pulmonary Function Test meets ATS quality criteria as determined by a central reviewer at the PFT Reading Core (UCLA) 2. Baseline (Visit 2) Pulmonary Function Test meets ATS quality criteria as determined by the central reviewer at the PFT Reading Core (UCLA), Site Investigator, or DEPTH Trial Leadership. * HIV-1 RNA level \< 200 copies/ml within 90 days prior to the Entry/Baseline visit by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent. * CD4 cell count \> 100 cells/mm3 within 90 days prior to the Entry/Baseline visit.by any US laboratory that has a CLIA certification or its equivalent. * Stable antiretroviral therapy for greater than or equal to 8 weeks prior to the Entry/Baseline visit. Substitutions of one formulation of a drug for another are not considered changes in antiretroviral therapy for the purpose of defining stable therapy.. * Serum ALT and AST \< 3 x upper limit of normal within 60 days prior to the Entry/Baseline visit. * Participants on therapy for COPD must be on stable therapy for at least 4 weeks prior to the Entry/Baseline visit. * Documentation of serum alpha-1-antitrypsin level above the lower limit of normal from a test done at any time prior to the Entry/Baseline visit. * Provision of signed and dated written informed consent. * Stated willingness to adhere to all study procedures and anticipated availability for the duration of the study. * Life expectancy \> 2 years in the opinion of the site investigator. * Ability to take oral medication and willingness to adhere to the study drug. * For individuals of reproductive potential, negative serum or urine pregnancy test with a sensitivity of less than or equal to 25 mIU/mL at the screening visit. This will be repeated at the Entry/Baseline visit. Exclusion Criteria: * Pulmonary infection, acute COPD exacerbation, acute opportunistic infection within 30 days prior to the Screening Visit 1 or Entry/Baseline Visit 2. * Any acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to the Entry/Baseline visit. * Decompensated cirrhosis defined as an acute deterioration in liver function in a patient with cirrhosis and is characterized by jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome or variceal hemorrhage. * History of, or planned, wedge resection, lobectomy, pneumonectomy, or lung volume reduction surgery. * History of, or planned, endobronchial valve placement for lung volume reduction. * Significant parenchymal lung disease other than emphysema or chronic bronchitis (e.g. sarcoidosis, MAI infection, pulmonary fibrosis, lung cancer, bullae/cysts from prior Pneumocystis pneumonia) that would preclude accurate quantification of emphysema. * Previous allergy or intolerance to doxycycline or other drugs in the tetracycline class (e.g. minocycline, tetracycline). * Breastfeeding individuals. * Receipt of any investigational\* drug within 30 days prior to the Entry/Baseline visit. Note: for the purpose of this protocol, investigational drug refers to a drug that is not FDA approved for any indication. COVID vaccines available under emergency use authorization are allowed. * Need for concomitant use of barbiturates; carbamazepine; phenytoin * Use of systemic retinoids (eg. Isotretinoin \[Accutane\]) or Vitamin A within 30 days prior to the Entry/Baseline visit. Note: Multivitamin containing Vitamin A use is permitted. * Use of any systemic antibiotic (e.g., doxycycline or other tetracycline, azithromycin) within 7 days prior to the Entry/Baseline visit. * Any condition including active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. * History of recurrent C. difficile infection or C. difficile infection within 30 days prior to the Entry/Baseline visit. * Inability to stop supplemental oxygen for 15 minutes to perform a DLCO maneuver. * Has changes to the chest that preclude adequate HRCT imaging (e.g. Metallic objects in the chest such as shrapnel or pacemaker leads) * Current receipt of, or anticipated need to initiate, hemodialysis or peritoneal dialysis.