CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: The rate of pulmonary function abnormalities is similar in both PHIV and PHEU youth. The lower rate of reversibility in PHIV compared to PHEU raises the possibility that respiratory symptoms in PHIV are misclassified as asthma. Further study is warranted to determine the nature and pathogenesis of the observed pulmonary function abnormalities. 802 Distinct Airway Methylation and Gene Expression Profiles in HIV-Associated COPD Janice M. Leung 1 ; EmilyVucic 2 ; Joseph C. Liu 1 ; David Ngan 1 ;Tawimas Shaipanich 3 ; Julio Montaner 4 ; Stephen Lam 2 ; Don Sin 1 ;Wan Lam 2 ; S. F. Paul Man 1 1 Centre for Heart Lung Innovation, Vancouver, Canada; 2 BC Cancer Research Center, Vancouver, Canada; 3 St. Paul’s Hospital, Vancouver, Canada; 4 BC Centre for Excellence in HIV/AIDS, Vancouver, Canada Background: Recent studies have identified an increased prevalence of chronic obstructive pulmonary disease (COPD) in HIV. Clinical manifestations of COPD in the HIV population appear to be more severe and develop earlier than in HIV-uninfected individuals. The underlying mechanism behind accelerated COPD in HIV is unknown. We hypothesize that airway epithelial DNA methylation and gene expression profiles in HIV-infected individuals can identify key molecular differences increasing the susceptibility to COPD. Methods: Airway epithelial cells were collected from HIV-infected smokers via bronchoscopic brushings. DNA methylation profiles of these cells were obtained using the Illumina Infinium 450K Human Methylation array. Gene expression profiles were obtained using the Affymetrix GeneChip ® Human Gene 2.0 ST array. Profiles were compared to HIV- uninfected smokers with and without COPD who were matched for age, sex, and smoking pack-years. DNA methylation and gene expression profiles were integrated whereby genes both hypomethylated and overexpressed or both hypermethylated and underexpressed were identified. Results: Airway epithelial cell profiles from 10 HIV-infected smokers (average age 63 years, 7 males), all with computed tomographic evidence of emphysema, were compared to those from 15 HIV-uninfected COPD patients and 22 HIV-uninfected non-COPD controls. Principal component analysis of the top 100 methylated genes demonstrated a distinct airway epithelial profile distinguishing HIV-infected patients from both uninfected COPD patients and uninfected normal controls (Figure 1). Integration of DNA methylation and gene expression profiles demonstrated upregulation of genes involved in oxidative stress pathways in HIV-infected patients ( DNAKA4 and DNAJC18 in the Nrf2 antioxidant stress response pathway), in contrast to HIV-uninfected COPD patients in whom proinflammatory pathways signaling through IL-17A predominated ( IL17RC and CSF2 ).

Poster Abstracts

Conclusions: DNA methylation and gene expression profiling of airway epithelial cells from HIV-infected patients reveal that increased oxidative stress may contribute to the heightened susceptibility to COPD. Targeting persistent oxidative stress may be a therapeutic option in future for mitigating age-related comorbidities such as COPD.

THURSDAY, FEBRUARY 26, 2015 Session P-Q11 Poster Session

Poster Hall

2:30 pm– 4:00 pm Body Composition and Risk Factors for Abnormalities 803 Altered Body Composition and Inflammation in HIV InfectionWith Type 2 Diabetes Malene Hove ; Julie Abildgaard; Julie C. Gaardbo; AllanVaag; Jan Gerstoft; Bente Klarlund Pedersen; Birgitte Lindegaard; Susanne D. Poulsen Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark

Background: Chronic inflammation is a constant finding in HIV infection. Likewise, inflammation plays a role in the pathogenesis of type 2 diabetes (T2D). Furthermore, T2D is linked with obesity, insulin resistance, and decreased levels of anti-inflammatory adipokines. Little is known about the combined effect of HIV infection and T2D on body composition and inflammation. We hypothesized that HIV-infected persons with T2D have altered fat distribution and higher level of inflammation compared to HIV-infected persons without T2D. Methods: Cross-sectional study including 36 HIV-infected persons on cART and with HIV RNA < 200 copies/mL (n=18 with T2D (HIV+T2D+), n=18 without T2D (HIV+T2D-)), and 44 HIV-negative persons (n=19 with T2D (HIV-T2D+) and n=25 without T2D (HIV-T2D-). Groups were matched on age and sex, and groups of HIV-infected persons on CD4 cell count (698 cells/mL vs. 656 cells/mL). DXA–scans were performed to evaluate fat distribution. Pro-inflammatory interleukin (IL)-6 and anti- inflammatory adiponectin were measured on snap-frozen plasma using Human IL-6 Kit V-PLEX and Human Adiponectin Assay. Differences between groups were analyzed using one-way ANOVA and t test. Data are given as mean (95%CI).

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CROI 2015