Factors associated with pulmonary impairment in HIV-infected South African adults

Abstract

BackgroundHIV-infected individuals have increased risk of developing obstructive lung disease (OLD). Studies from developed countries report high viral load, low CD4 counts, and anti-retroviral therapy (ART) to be associated with OLD; but these findings may not be generalizable to populations in resource-limited settings.MethodsWe conducted a prospective cohort study of lung function in 730 HIV-infected black South African adults. Pre-bronchodilator spirometry was performed at enrollment and repeated annually for three years. Logistic regression models were used to identify factors associated with OLD, defined as FEV1/FVC<0.70, at enrollment. Excess annual declines in FEV1 and FVC were modelled as the product-term of follow-up time and exposures using random effects regression.ResultsMedian (IQR) age at enrollment was 36 (32–41) years, 85% were female and 30% ever-smoked with a median (IQR) exposure of 3 (1–6) pack-years. Median (IQR) CD4 count and viral load at enrollment were 372 (261–518) cells/mm3 and 2655 (91–13,548) copies/mL respectively. Overall, 25% were receiving ART at enrollment, 16% of whom reported at least 6 months of ART receipt. OLD was found in 35 (5%) at enrollment. Increasing age (aOR = 2.08 per 10-years [95%CI 1.22–3.57], p = 0.007), current smoking (aOR = 3.55 [95%CI 1.20–10.53], p = 0.02), and CRP (aOR = 1.01 per unit-increase [95%CI 1.00–1.03], p = 0.04) were significantly associated with OLD at enrollment; while increasing CD4 count (aOR = 1.02 per-100 cells/mm3 [95%CI 0.85–1.22], p = 0.82), viral load (aOR = 0.67 per log-increase [95%CI 0.43–1.10], p = 0.12) and receipt of ART (aOR = 0.57 [95%CI 0.18–1.75], p = 0.32) were not. The median (IQR) follow-up time was 18 (12–24) months. Participants with a history of tuberculosis (TB) had a 35 mL (95%CI 2–68, p = 0.03) and 57 mL (95%CI 19–96, p = 0.003) per year excess loss of FEV1 and FVC respectively.ConclusionPrevalent OLD was associated with older age, current smoking and higher CRP levels, but not CD4 counts and ART, in HIV-infected South African adults. Better understanding of the long-term effects of TB, smoking and inflammation on lung function in HIV-infected populations is urgently needed.

Associations between baseline biomarkers and lung function in HIV-positive individuals

“…Other biomarkers were not analyzed in that study. [32] Although markers of systemic inflammation have been associated with a multitude of COPD and HIV-related outcomes, our finding that there was not association with longitudinal lung function decline has precedent. In an analysis of 1793 participants in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study several biomarkers, including CRP and fibrinogen (a marker of coagulation) were associated with baseline FEV 1 however only Club Cell 16 (CC16), a pulmonary specific biomarker, was associated with longitudinal FEV 1 decline.…”

Non-communicable respiratory disease and air pollution exposure in Malawi: a prospective cohort study

“…The lung function trajectories of adults from sub-Saharan Africa (sSA) are largely undescribed; limited published data relate to cohorts from South Africa with HIV-infection and occupational silica dust exposure 8 9. There are no data from population-representative cohorts in sSA; it is not known whether adults exposed to biomass-related air pollution would experience accelerated age-related decline in lung function and therefore an increased risk of developing obstructive airways diseases as occurs in those exposed to tobacco smoke 10 11…”

The Immune Mechanisms of Lung Parenchymal Damage in Tuberculosis and the Role of Host-Directed Therapy

“…Globally, 13 percent of people with active TB who know their HIV status are co-infected with HIV-1 ( World Health Organization, 2017 ). Although TB is also a risk factor for airflow obstruction in patients with HIV ( Samperiz et al, 2014 ; Pefura-Yone et al, 2015 ; Gupte et al, 2017 ), in HIV positive patients with a low CD4 count (CD4 < 200/mm 3 ) TB often presents with atypical CXR findings or even normal CXRs, while cavitation is 4-fold less common ( Kwan and Ernst, 2011 ). These findings suggest that TB-related pulmonary damage might be reduced in HIV co-infected patients and the host immune response, necessary for protection against TB, is required for the development of cavities.…”