Pulmonary Function Trajectories in People with HIV: Analysis of the Pittsburgh HIV Lung Cohort

Rationale: Human immunodeficiency virus (HIV) infection is associated with chronic lung disease and impaired pulmonary function; however, longitudinal pulmonary function phenotypes in HIV are undefined. Objectives: To identify pulmonary function trajectories, their determinants, and outcomes. Methods: We used data from participants with HIV in the Pittsburgh HIV Lung Cohort with three or more pulmonary function tests between 2007 and 2020. We analyzed post-bronchodilator forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and FEV₁/FVC, and diffusing capacity of the lung for carbon monoxide (Dl_CO) using group-based trajectory modeling to identify subgroups of individuals whose measurements followed a similar pattern over time. We examined the association between participant characteristics and trajectories using multivariable logistic regression. In exploratory adjusted analyses restricted to individuals with available plasma cytokine data, we investigated the association between 18 individual standardized cytokine concentrations and trajectories. We compared mortality, dyspnea prevalence, respiratory health status, and 6-minute-walk distance between phenotypes. Results: A total of 265 participants contributed 1,606 pulmonary function measurements over a median follow-up of 8.1 years. We identified two trajectories each for FEV₁ and FVC: "low baseline, slow decline" and "high baseline, rapid decline." There were three trajectory groups for FEV₁/FVC: "rapid decline," "moderate decline," and "slow decline." Finally, we identified two trajectories for Dl_CO: "baseline low" and "baseline high." The low baseline, slow decline FEV₁ and FVC, rapid decline, and moderate decline FEV₁/FVC, and baseline low Dl_CO phenotypes were associated with increased dyspnea prevalence, worse respiratory health status, and decreased 6-minute-walk distance. The baseline low Dl_CO phenotype was also associated with worse mortality. Current smoking and pack-years of smoking were associated with the adverse FEV₁, FEV₁/FVC, and Dl_CO phenotypes. Detectable viremia was the only HIV marker associated with the adverse Dl_CO phenotype. C-reactive protein and endothelin-1 were associated with the adverse FEV₁ and FVC phenotypes, and endothelin-1 trended toward an association with the adverse Dl_CO phenotype. Conclusions: We identified novel, distinct longitudinal pulmonary function phenotypes with significant differences in characteristics and outcomes. These findings highlight the importance of lung dysfunction over time in people with HIV and should be validated in additional cohorts.