HIV infection is associated with elevated biomarkers of immune activation in Ugandan adults with pneumonia.

INTRODUCTION: Pneumonia is an important cause of morbidity and mortality in persons living with human immunodeficiency virus (HIV) infection. How immune activation differs among HIV-infected and HIV-uninfected adults with pneumonia is unknown. METHODS: The Inflammation, Aging, Microbes, and Obstructive Lung Disease (I AM OLD) Cohort is a prospective cohort of adults with pneumonia in Uganda. In this cross-sectional analysis, plasma was collected at pneumonia presentation to measure the following 12 biomarkers: interleukin 6 (IL-6), soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2), high sensitivity C-reactive protein (hsCRP), fibrinogen, D-dimer, soluble CD27 (sCD27), interferon gamma-inducible protein 10 (IP-10), soluble CD14 (sCD14), soluble CD163 (sCD163), hyaluronan, and intestinal fatty acid binding protein. We asked whether biomarker levels differed between HIV-infected and HIV-uninfected participants, and whether higher levels of these biomarkers were associated with mortality. RESULTS: One hundred seventy-three participants were enrolled. Fifty-three percent were HIV-infected. Eight plasma biomarkers-sTNFR-1, sTNFR-2, hsCRP, D-dimer, sCD27, IP-10, sCD14, and hyaluronan-were higher among participants with HIV infection, after adjustment for pneumonia severity. Higher levels of 8 biomarkers-IL-6, sTNFR-1, sTNFR-2, hsCRP, IP-10, sCD14, sCD163, and hyaluronan-were associated with increased 2-month mortality. CONCLUSIONS: As in other clinical contexts, HIV infection is associated with a greater degree of immune activation among Ugandan adults with pneumonia. Some of these are also associated with short-term mortality. Further study is needed to explore whether these biomarkers might predict poor long-term outcomes-such as the development of obstructive lung disease-in patients with HIV who have recovered from pneumonia.

Pneumoproteins are associated with pulmonary function in HIV-infected persons.

BACKGROUND: COPD is a common HIV comorbidity, and HIV-infected individuals have a higher incidence and earlier onset of COPD compared to HIV-uninfected individuals. While the pathogenesis of HIV-associated COPD is largely unknown, chronic inflammation may contribute. Four pneumoproteins known to be markers of lung injury and inflammation have been associated with COPD in HIV-uninfected individuals: PARC/CCL-18, SP-D, CC-16, and sRAGE. OBJECTIVE: To determine whether these pneumoproteins are also associated with pulmonary function and COPD Assessment Test (CAT) scores in HIV-infected individuals. METHODS: Associations between plasma pneumoprotein levels and pulmonary function were determined in a cross-sectional study of otherwise healthy HIV-infected individuals enrolled between September 2016 and June 2017. Covariates included HIV-associated (antiretroviral therapy, CD4 count, and viral load) and COPD-associated (smoking and BMI) covariates. RESULTS: Among 65 participants, 78.5% were male, 50.8% had undetectable viral load, and 76.9% were ever-smokers. Mean post-bronchodilator FEV1/FVC was 0.71, and mean DLco%predicted was 61%. Higher PARC/CCL-18 was associated with lower DLco%predicted and higher CAT score. Higher CC-16 was associated with lower DLco%predicted and lower FVC%predicted. CONCLUSIONS: This exploratory analysis is the first to characterize associations between these four pneumoproteins and pulmonary function in an HIV-infected cohort. Our findings suggest the pathogenesis of HIV-associated COPD may differ from that of non-HIV-associated COPD due to HIV-specific inflammatory changes affecting DLco. PARC/CCL-18 is associated with structural and functional pulmonary abnormalities and may be an important COPD biomarker candidate in HIV infection. Our study is a preliminary step toward finding clinically relevant COPD biomarkers in high-risk populations.