Moderate to Severe Impairment of D l CO and Iso↓D l CO Are Associated with All-Cause Mortality in People with Human Immunodeficiency Virus

Rationale The most common lung function abnormality in people with human immunodeficiency virus (HIV) (PWH) is a low diffusing capacity of the lung for carbon monoxide (Dl CO), which is associated with distinct plasma biomarker patterns, increased symptom burden, and increased mortality. In PWH undergoing spirometry and Dl CO measurement, the most common abnormality is an abnormal Dl CO with normal spirometry (iso↓Dl CO), which is associated with distinct biomarkers and increased symptom burden but whose association with mortality is unknown. Objectives To investigate the relationship between abnormal Dl CO, including iso↓Dl CO, and mortality in PWH. Methods Adult PWH underwent pre and postbronchodilator spirometry and single-breath Dl CO measurements from April 2013 to January 2023. Dl CO was categorized as normal (Dl CO greater than or equal to the lower limit of normal [LLN]), mildly abnormal (60% predicted < Dl CO < LLN), or moderately to severely abnormal (Dl CO ≤60% predicted). Iso↓Dl CO was defined as abnormal Dl CO with normal spirometry (forced expiratory volume in 1 second/forced vital capacity ≥ LLN, forced expiratory volume in 1 second ≥ LLN, forced vital capacity ≥ LLN). Participants’ present vital status was assessed through electronic health record review and the National Death Index. Multivariable Cox proportional hazards models adjusted for age, smoking status, history of bacterial pneumonia, and CD4 count were used to estimate associations between Dl CO and all-cause mortality. Results Among 241 participants, 205 (85%) were male and 26 (11%) died during follow-up of 1,055 person-years. Among 178 participants with normal spirometry, 16 (9%) died over 770 person-years. Both moderate to severe Dl CO impairment (adjusted hazard ratio, 4.67; 95% confidence interval, 1.69–12.9; P = 0.003) and moderate to severe iso↓Dl CO (adjusted hazard ratio, 11.0; 95% confidence interval, 2.20–55.1; P = 0.004) were significantly associated with increased mortality. Conclusions Moderate to severe impairment of Dl CO and iso↓Dl CO are associated with all-cause mortality in PWH. Further studies evaluating mechanistic pathways and cause-specific mortality are warranted.