CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: sCD163, IL-6 and hsCRP are associated with lower lung function in older age PLWH in rural Uganda. Further work is necessary to understand the mechanisms underlying differences in systemic inflammatory profiles among PLWH in sub-Saharan Africa and other non-African HIV cohorts.

Background: The reported prevalence of Chronic Obstructive Pulmonary Disease(COPD) in people living with HIV(PLWH) varies widely(7-60%) depending on the study population and methods used, underscoring the uncertainty of the estimates. Our objective was to estimate the prevalence of COPD in unselected PLWH and identify characteristics that increase the risk of non-reversible airflow obstruction using spirometry-the gold standard-in order to guide screening strategies for COPD. Methods: This study was conducted at the Chronic Viral Illness Service at the McGill University Health Centre in Montreal, Canada(population≈2000 PLWH). All persons ≥18 years of age with HIV were invited to participate, regardless of smoking status or history of known COPD/asthma. Individuals with acute respiratory infection were excluded. Individuals underwent standard spirometric testing both pre and post salbutamol bronchodilator and completed the MRC dyspnea scale, which rates the severity of dyspnea on a scale of 1-5. The presence of COPD(FEV1/FEV<0.7 post-bronchodilator) was determined and multivariate logistic regression was used to evaluate risk factors associated with COPD, reported as adjusted odds ratios(aOR). Results: There were 369 participants of whom 39(11%) had COPD on spirometry. Median age (Q1;Q3) was 51(44;58), and 30%were female. Most were Caucasian(57%), followed by Black African (22%). Participants had a median duration of HIV of 15 years(9; 22) and 94%were on antiretrovirals for a median duration of 10(6;16) years with 92% virally suppressed. Median CD4 count was 594(440;786) and nadir CD4 count was 234 (128;376) cells/uL. Median MRC dyspnea score was 1(1;2), implying a low burden of dyspnea. Results of spirometry testing are depicted in Table 1 and demonstrate a high proportion of patients with reversible airflow obstruction. The following risk factors for COPD were assessed: smoking history(aOR: 2.96, 95% CI: [1.36; 7.03]), age(2.02 [1.41; 2.97]), female sex(0.72 [0.23; 1.9]), and higher nadir CD4 count(0.85 [0.69; 1.03] per 100 cells). Conclusion: Both smoking status and older age independently predicted the presence of non-reversible airflow obstruction in PLWH. Low nadir CD4 appeared to be associated with the presence of COPD. These findings suggest that PLWH who are ≥50 years, smokers and those with nadir CD4 counts ≤200 cells/µL should undergo spirometry screening for COPD. The high rate of reversible airflow obstruction is a novel finding and merits further exploration.

749 DIFFERENCES IN THE ADENOSINE SIGNALING PATHWAY AMONG HIV+ INDIVIDUALS WITH COPD Kiran Bandi , Seyed M. Nouraie, Edwin Jackson, Peter Nam, Delbert Gillespie, Cynthia Klamar-Blain, Cathy Kessinger, Sharon Riddler, Alison Morris, Bernard J. Macatangay University of Pittsburgh, Pittsburgh, PA, USA Background: Aberrant purinergic signaling is believed to play a role in COPD pathogenesis. CD39 has ATPase activity and is hypothesized to be protective in cigarette smoke-induced lung damage. CD73 is the rate-limiting enzyme that breaks down AMP to adenosine (ADO), which in turn has anti-inflammatory effects. CD26 binds ADO deaminase which metabolizes ADO and can influence extracellular ADO levels. Methods: Using flow cytometry, we evaluated differences in the expression of CD39, CD73, and CD26 on peripheral CD4+/CD8+ T cells among ART-treated HIV(+) and HIV(-) individuals with and without COPD [HIV(+)COPD(+) n=16; HIV(+)COPD(-) n=14; HIV(-)COPD(+) n=11; HIV(-COPD(-) n=12], and determined whether expression is associated with plasma levels of inosine (surrogate for ADO; INO) obtained by mass spectrometry and with pulmonary function testing (PFT; forced expiratory volume, FEV1; forced vital capacity; diffusing capacity). Results: With CD39 expression, HIV(-)COPD(+) had a trend for increased %CD4+CD39+ T cells compared to HIV(-)COPD(-) [12.7% vs 8.7, p=0.07; Kruskal- Wallis with Dunn’s post-test]. However, HIV(+)COPD(+) did not have higher %CD4+CD39+ T cells compared to HIV(+)COPD(-). There were no associations between CD39 expression and PFTs. With CD73 expression, HIV(+) participants with or without COPD, had lower %CD4+CD73+ [p values=0.004-0.006] and %CD8+CD73+ [p values=0.001-0.015] compared to all HIV(-) participants. In all participants with COPD, %CD8+CD73+ T cells significantly correlated with FEV1 (Spearman r=0.45, p=0.01). This correlation was not observed among all COPD(-) participants. Expression of CD39 or CD73 did not correlate with plasma INO levels. With CD26 expression, HIV(+)COPD(+) had lower %CD4+CD26+ than HIV(+)COPD(-) [p=0.035], HIV(-)COPD(+) [p=0.0005], and HIV(-)COPD(-) [p=0.02]. Similarly, %CD8+CD73+ was lower in the HIV(+)COPD(+) group compared to the HIV(-) groups, but similar to the HIV(+)COPD(-) group. In all participants, %CD4+CD26+ T cells modestly correlated with INO levels (r=0.25, p=0.09); among all COPD(+) participants, INO levels in turn, modestly correlated with FEV1 (r=0.35, p=0.06). Conclusion: Compared to HIV(-)COPD(+) individuals, HIV(+)COPD(+) individuals do not have increased CD39 expression relative to HIV(+)COPD(-) individuals and have lower frequencies of CD4+ and CD8+ T cells expressing CD73 or CD26. Given these differences, COPD therapeutic strategies targeting the ADO signaling pathway may result in different outcomes for the HIV(+) population. 750 PREDICTORS OF AIRFLOW OBSTRUCTION IN AN HIV TERTIARY CARE CLINIC Cecilia Costiniuk 1 , Roy Nitulescu 1 , Christina de Castro 1 , Natale Wasef 1 , Syim Salahuddin 1 , Jean-Pierre Routy 1 , Bertrand Lebouché 1 , Joseph Cox 1 , Benjamin M. Smith 1 , Jason Szabo 1 , Alexandra de Pokomandy 1 , Chris Tsoukas 2 , Mohammad-Ali Jenabian 3 , Jean Bourbeau 1 , Marina Klein 1 1 McGill University Health Centre, Glen site, Montreal, QC, Canada, 2 McGill University, Montreal, QC, Canada, 3 Université du Québec à Montréal, Montreal, QC, Canada

Poster Abstracts

751 HIV IS INDEPENDENTLY ASSOCIATED WITH HIGHER ALPHA-1 ANTITRYPSIN

Rebekka F. Thudium 1 , Jens D. Lundgren 1 , Børge Nordestgaard 2 , Jan Gerstoft 1 , Susanne D. Nielsen 1 , Andreas Ronit 1 1 Rigshospitalet, Copenhagen, Denmark, 2 University of Copenhagen, Copenhagen, Denmark Background: Alpha-1 Antitrypsin (AAT) is the most abundant circulating serine protease inhibitor and its main function is to protect the lung against proteolytic damage. Little is known about AAT in people living with HIV (PLWH), but in theory: i) AAT may be associated with lower pulmonary function, ii) as an inducer of HIV inhibition in vitro, AAT may be associated with immune status, iii) as an acute phase reactant, AAT may be a novel biomarker for non-AIDS events. We measured AAT in PLWH and in uninfected controls and studied associations with pulmonary function and CD4 T-cell counts. Methods: Using data from the Copenhagen comorbidity in HIV infection (COCOMO) study we assessed AAT levels in PLWH and age and sex matched uninfected controls. Low AAT was defined as below 1.0 g/L. Pulmonary function was measured by spirometry and airflow obstruction was defined by the lower limit of normal (LLN) of FEV1/FVC and by FEV1/FVC<70% plus FEV1-predicted <80% (fixed). We assessed whether AAT to a greater extend contribute to low FEV1-predicted in PLWH than in uninfected controls by studying the interaction

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