CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

661 HIV IS ASSOCIATED WITH LUNG-FUNCTION IMPAIRMENT IN THE MULTICENTER AIDS COHORT STUDY

Ken M. Kunisaki 1 , Seyed M. Nouraie 2 , Robert Jensen 3 , Dong Chang 4 , Gypsyamber D’Souza 5 , Meghan E. Fitzpatrick 2 , Meredith C. McCormack 6 , Valentina Stosor 7 , Alison Morris 2 , for the MACS Pulmonary Substudy Group 1 Minneapolis VA Health Care System, Minneapolis, MN, USA, 2 University of Pittsburgh, Pittsburgh, PA, USA, 3 University of Utah, Salt Lake City, UT, USA, 4 Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance, CA, USA, 5 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 6 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 7 Northwestern University, Chicago, IL, USA Background: HIV is an independent risk factor for chronic obstructive pulmonary diease (COPD), a major cause of death and disability worldwide. Although studies have measured lung function in persons living with HIV (PLWH), major limitations have included small samples, lack of HIV-negative controls or limited lung function assessment. We addressed these weaknesses by collecting spirometry (both pre- and post-bronchodilation) and single- breath diffusing capacity for carbon monoxide (DLCO) in a multicenter cohort of men who have sex with men (MSM), both HIV-positive and HIV-negative. Methods: We included participants in the Multicenter AIDS Cohort Study seen between April 2017 - March 2018. Spirometry and DLCO were measured using standardized equipment, according to published standards, centrally reviewed for quality, and normalized (calculation of %predicted values) using published population-based equations. We tested the effect of HIV status on %predicted post-bronchodilator forced expiratory volume in 1s (FEV1) and DLCO, both as continuous outcomes and as categorical outcomes (<80% of predicted). Multivariable models were adjusted for cigarette smoking, illicit drug use, and co-infection with hepatitis B or C. Results: Among 1305 participants who attended research visits, 1176 (90.1%) completed lung function testing. Quality control standards were met for 1126 spirometry tests and 1094 DLCO tests. PLWH were younger, less likely to be Caucasian, reported more illicit drug use, and more commonly had hepatitis co-infection (each p<0.01). We observed no difference in FEV1 %predicted by HIV status (adjusted difference of 0.9% of predicted; 95%CI: -3.1% to +1.2%; p=0.40), but DLCO %predicted was significantly lower in PLWH (adjusted difference of -2.5% of predicted; 95%CI: -4.4 to -0.6%; p=0.009) (Table). PLWH were more likely to have DLCO <80% of predicted (OR 1.56; 95%CI: 1.17 to 2.09; p=0.003). Among the HIV-positive participants, lower DLCO values were correlated with lower nadir CD4+ T-cell count (adjusted β = 0.27; p=0.016) and borderline for increasing years of ART exposure (adjusted β = -1.2; p=0.063). Conclusion: Compared to HIV-negative MSM, HIV-positive MSM are at higher risk for impaired DLCO, but not airway obstruction. While mechanisms of DLCO impairment in PLWH are unclear, worse DLCO in PLWH has been linked to mortality and decreased functional status, suggesting it is an important health issue in this population.

660 EVIDENCE OF PRECLINICAL MYOCARDIAL FIBROSIS IN ART-TREATED PLWH IN SOUTH AFRICA Lye-Yeng Wong 1 , Tess Peterson 2 , Julian Wolfson 3 , Justin A. Lumbamba 4 , Stephen Jermy 4 , Hadil Saad 4 , Scott Shuldiner 5 , Muki Shey 4 , Graeme Meintjes 4 , Ntobeko Ntusi 4 , Mpiko Ntsekhe 4 , Jason V. Baker 2 1 Dartmouth–Hitchcock Medical Center, Lebanon, NH, USA, 2 Hennepin County Medical Center, Minneapolis, MN, USA, 3 University of Minnesota, Minneapolis, MN, USA, 4 University of Cape Town, Cape Town, South Africa, 5 Johns Hopkins University, Baltimore, MD, USA Background: Cardiovascular disease (CVD) risk is higher among persons living with HIV (PLWH), based on data from U.S. and Europe showing excess risk for atherosclerotic coronary heart disease. In sub-Saharan Africa, hypertension and heart failure are the predominant CVD manifestations, where the influence from ART-treated HIV disease remains less clear. Methods: Asymptomatic PWLH on ART and uninfected controls, both without known heart failure, were enrolled in Khayelitsha, Cape Town, South Africa. Roche immunoassays estimated biomarker levels for myocardial injury (high sensitivity troponin T [cTnT] via 5th Gen) and dysfunction (NT-pro brain natriuretic peptide [NTproBNP]). PLWH then had BNP levels measured by point of care (POC) Abbott iSTAT ELISA, and cardiac magnetic resonance (CMR) imaging was performed. Biomarker elevations were defined using thresholds of: >6.0ng/L for cTnT (i.e., a detectable level), and >100pg/mL for NT-proBNP (90% sensitive for dysfunction among those <70 years old) and POC BNP (manufacturer threshold). Linear and log binomial regression was used to assess associations between biomarkers, HIV status, and CMR measures. Results: Among 49 PLWH and 57 uninfected controls, respectively, median (IQR) age was 46 (43-53) and 50 (45-57), 61% and 63%were women, and 33% and 37%were hypertensive. Among PLWH, median (IQR) CD4+ count was 515 cells/μL (334-677), and 78% had HIV RNA <50 copies/mL. No participants had evidence of ischemic disease on ECG (Q-waves or LBBB). PLWH, versus uninfected controls, had a higher proportion with NT-proBNP levels >100pg/ mL (33% vs. 19%; p=0.04) but differences in detectable cTnT were not statistically significant (45% vs. 32%; p=0.15). The proportion of PLWH with POC BNP >100pg/mL was 14%, and NT-proBNP and POC BNP levels were highly correlated (r=0.89; p<0.0001). The data table reports associations for cardiac biomarkers and CMR measures among PLWH. Elevated NT-proBNP and POC BNP levels tended to be associated with parameters reflecting myocardial inflammation and fibrosis (i.e., ECV, LGE, native T1), some measures of diastolic dysfunction, (i.e., strain rates) but not systolic dysfunction (i.e., EF). Conclusion: These pilot data suggest that PLWH in South Africa may have ongoing myocardial inflammation and fibrosis and pre-clinical myocardial dysfunction. Future research should focus on understanding the mechanisms and clinical relevance of HIV-associated myocardial injury in sub-Saharan Africa.

Poster Abstracts

CROI 2019 251