Associations Between Baseline Biomarkers and Lung Function in HIV-positive Individuals

Objective: The aim of this study was to analyse the association of baseline biomarker data with cross-sectional lung function and subsequent decline in lung function in HIV-positive persons.

Design: Lung function was modelled in all START pulmonary substudy participants who had baseline biomarker data and good-quality spirometry. In longitudinal analyses, we restricted to those participants with at least one good-quality follow-up spirometry test.

Methods: We performed linear regression of baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC and their longitudinal slopes on log2-transformed baseline biomarkers with adjustment for age, sex, race, region, smoking status, baseline CD4+ T-cell counts and baseline HIV-RNA. Biomarkers included D-dimer, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-27, serum amyloid A, soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1, albumin and total bilirubin.

Results: Among 903 included participants, baseline median age was 36 years, CD4+ cell count was 647 cells/μl, and 28.5% were current smokers. In adjusted analyses, elevated markers of systemic inflammation (hsCRP, IL-6 and serum amyloid A) were associated with lower baseline FEV1 and FVC. Elevated D-dimer and IL-6 were associated with worse airflow obstruction (lower FEV1/FVC). Despite these cross-sectional associations at baseline, no associations were found between baseline biomarkers and subsequent longitudinal lung function decline over a median follow-up time of 3.9 years (3293 spirometry-years of follow-up).

Conclusion: Commonly available biomarkers, in particular markers of systemic inflammation, are associated with worse cross-sectional lung function, but do not associate with subsequent lung function decline among HIV-positive persons with early HIV infection and baseline CD4 T-cell counts more than 500 cells/μl.