Moderate-to-Severe Impairment of DLCO and iso↓DLCO Are Associated with All-Cause Mortality in People with HIV.

Abstract

Rationale The most common lung function abnormality in people with HIV (PWH) is a low diffusing capacity 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. Objective: To investigate the relationship between abnormal DL_CO, including iso↓DL_CO, and mortality in PWH. Methods Adult PWH underwent pre- and post-bronchodilator spirometry and single-breath DL_CO measurements from April 2013-January 2023. DL_CO was categorized as normal (DL_CO≥lower limit of normal, LLN), mildly abnormal (60%predicted≤DL_COCO≤60%predicted). Iso↓DL_CO was defined as abnormal DL_CO with normal spirometry (FEV1/FVC≥LLN, FEV1≥LLN, FVC≥LLN). Participants' present vital status was assessed through electronic health records 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 1055 person-years. Among 178 participants with normal spirometry, 16 (9%) died over 770 person-years. Both moderate-to-severe DL_CO impairment (aHR 4.67; 95%CI 1.69-12.9; p=0.003) and moderate-to-severe iso↓DL_CO (aHR 11.0; 95% CI 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.