Systemic Inflammation, Immune Activation and Impaired Lung Function among People Living with HIV in Rural Uganda

Abstract

Background—Although both chronic lung disease and HIV are inflammatory diseases common in sub-Saharan Africa, the relationship between systemic inflammation and lung function among people living with HIV (PLWH) in sub-Saharan Africa is not well described. Methods—We measured lung function (using spirometry) and serum high sensitivity C-reactive protein, IL-6, sCD14 and sCD163 in 125 PLWH on stable antiretroviral therapy and 109 age and sex-similar HIV-uninfected controls in rural Uganda. We modeled the relationship between lung function and systemic inflammation using linear regression, stratified by HIV serostatus, controlled for age, sex, height, tobacco and biomass exposure. Results—Half of subjects (46%, [107/234]) were women and the median age was 52 years (IQR 48–55). Most PLWH (92%, [115/125]) were virologically suppressed on first-line antiretroviral therapy. Median CD4 count was 472 cells/mm3. In multivariable linear regression models stratified by HIV serostatus, an interquartile range increase in IL-6 and sCD163 were each inversely associated with lung function (mL, 95% confidence interval) among PLWH (IL-6: FEV1 −18.1 (−29.1, −7.1), FVC −17.1 (−28.2, −5.9); sCD163: FVC −14.3 (−26.9, −1.7)). hsCRP (>3mg/L vs. <1mg/L) was inversely associated with lung function among both PLWH and HIV-uninfected controls (PLWH: FEV1 −39.3 (−61.7, −16.9), FVC −44.0 (−48.4, −6.4); HIV-uninfected: FEV1 −37.9 (−63.2, −12.6), FVC −58.0 (−88.4, −27.5)). sCD14 was not associated with lung function, and all interaction terms were insignificant. Conclusions—Macrophage activation and systemic inflammation are associated with lower lung function among PLWH on stable antiretroviral therapy in rural Uganda. Future work should focus on underlying mechanisms and public health implications.