CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

1 Univ Coll Dublin, Dublin, Ireland, 2 Univ of California Los Angeles, Los Angeles, CA, USA, 3 Mater Misericordiae Univ Hosp, Dublin, Ireland Background: Dysfunction of monocytes (MNC) and HDL despite potent ART may be a major contributor to cardiovascular disease (CVD) risk in HIV infection. HIV+ patients have HDL with reduced antioxidant function (high HDL redox activity; HRA) and impairment in ABCA1-mediated MNC cholesterol efflux (MCE). Limited data exists on the effect of ART initiation on HDL and MNC function. We examined the effect of ART initiation on MCE and HRA. Methods: In a prospective cohort study we compared MCE and HRA in HIV+ subjects with low overall CVD risk pre and post ART initiation to HIV- controls matched for age, gender, ethnicity, smoking and viral hepatitis status. Subjects’ monocytes were isolated from fasting whole blood using anti-CD14+ conjugated magnetic beads and loaded in vitro with human LDL cholesterol from health donors (HD). MNC intracellular (MIC) and extracellular (EC) cholesterol were then measured by fluorescence at fixed time points over 24 hours in the presence and absence of apoA1 from HD (ABCA1-mediated efflux). Higher EC:MIC ratios indicate greater MCE. HDL function was assessed using a HRA assay normalized to HDL amount and a pooled control from HD (nHRA, no units). Data are median [IQR] and non-parametric analyses used. Results: One hundred subjects, 50 HIV+ (age 35 [29, 41] years, 80%male, 76%white, CD4+T cells 410 (268, 588) cells/mm3, log HIVRNA 4.01 (3.52, 4.78), Framingham 10yr CDV risk 1.8 [0.5, 6]%) and 50 HIV- controls (age 35 [30, 43] years, 78%male, 76%white, CVD risk 1.8 [0.9, 4.9]%) were recruited with repeat assessments on 20 HIV+ subjects 17 (13, 18) months post viral suppression with ART (CD4+T cells 627 (458, 836) cells/mm3). Although the untreated HIV+ group had unexpectedly higher MCE compared to controls (1.27 [1.06, 1.50] versus 1.13 [0.92, 1.35] p=0.05), ART was associated with further increased MCE compared to both untreated HIV+ (1.89 [1.55, 2.4], p<0.0001) and controls (p<0.0001). nHRA was higher in untreated HIV+ compared to controls (1.08 [0.86, 1.34] versus 0.84 [0.74, 0.96]; p<0.0001) and reduced with ART (0.84 [0.76, 0.99]; p<0.0001) to levels similar to controls (p=0.2) Conclusion: This is the first study to explore the impact of ART on both MNC and HDL function. Untreated HIV is associated with both increased MNC cholesterol efflux and dysfunctional HDL. While ART initiation was associated with improvements in antioxidant HDL function, MNC cholesterol efflux remained increased. The impact of these changes on CVD progression remains to be determined. 614 CHOLESTEROL EFFLUX RESPONDS TO THE IMMUNE STATUS IN PROGRESSION OF HIV INFECTION Olivia Tort 1 , Roque Pastor 1 , Felipe Garcia 2 , Esteban Martinez 2 , Montserrat Plana 2 , Tuixent Escribà 1 , Montserrat Cofán 1 , Emma Fernández 2 , Jose M. Gatell 2 , Mireia Arnedo 1 1 IDIBAPS, Barcelona, Spain, 2 Hosp Clinic of Barcelona, Barcelona, Spain Background: Cholesterol efflux capacity (CEC) is an emerging cell-based assay that successfully predicts cardiovascular events in the general population and could be used as a biomarker of atherosclerosis. Uncontrolled HIV infection is associated with impaired CEC, which can be everted with antiretroviral therapy. The potential influence of different immunological or virological HIV conditions on CEC may help to understand better the pathogenesis of atherosclerosis in HIV-infected patients. With this aim, we compared CEC, lipoprotein levels and immunological and inflammatory markers in HIV-infected patients at different stages of disease progression and HIV-exposed seronegative individuals. Methods: In this cross-sectional study we assessed a cholesterol efflux capacity (CEC) assay to evaluate high density lipoprotein (HDL) functionality of ApoB-depleted plasma. CEC, plasma lipids, cholesterol, lipoproteins, viral load, inflammatory biomarkers (high-sensitive C-reactive protein (hsCRP) and Lipoprotein(a)), CD4-T and CD8-T cell counts were evaluated in four groups of patients: untreated HIV infected patients (UHIV; n=44), elite controllers (EC; n=8), HIV-exposed seronegative individuals (HESN; n=32) and healthy control individuals (HC; n=14). Results: Among UHIV, those with CD4<450 presented the significant lowest CEC, HDL-C and ApoAI levels. EC showed similar HDL-C, ApoAI and CEC compared to HC. Among HIV-infected individuals (UHIV and EC), CEC positively correlated with current CD4+ T cell counts (Pearson r=0.58, p<0.0001) and inversely with current plasma HIV-1 RNA levels (Pearson r=-0.58, p<0.0001). However, HESN presented significantly higher CEC (0.78±0.14) than UHIV (0.65±0.17; p=0.0005), but lower than HC (0.90±0.13; p=0.009). hsCRP levels were higher in the groups of HIV-infected patients (UHIV and EC) compared to uninfected (HESN and HC; p=0.01). hsCRP partially and negatively correlated with CEC (Spearman r=-0.27; p=0.007). Lipoprotein(a) showed no significant differences between groups (p=0.47). Conclusion: We found low CEC in HIV-infected patients associated with lower CD4, higher plasma HIV-1 RNA, and higher hsCRP. CEC was also lower in HESN as compared with HC. Our results suggest that inflammation or immune status secondary to HIV infection or exposition to HIV may influence HDL functionality. 615 LOWER RATES OF CVD PROCEDURES IN HIV-INFECTED PATIENTS WITH ACUTE CORONARY SYNDROME Meredith Clement 1 , Li Lin 2 , Ann M. Navar 1 , Nwora L. Okeke 1 , Susanna Naggie 1 , Pamela Douglas 1 1 Duke Univ, Durham, NC, USA, 2 Duke Clinical Rsr Inst, Durham, NC, USA Background: Cardiovascular disease (CVD) is an increasing cause of morbidity and mortality in adults with HIV infection. HIV-infected patients have been shown to be less likely to receive treatment with procedures and surgery in the setting malignancy and orthopaedic disease. The degree to which disparities exist for CVD interventions is unknown. Methods: We compared rates of cardiac catheterization and revascularization (including percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery) among HIV-infected and uninfected adults hospitalized with acute coronary syndrome (ACS) from 2009-2012. We used the National Inpatient Sample (NIS), a dataset that includes information on 8 million hospital discharges per year, for our analysis. ICD-9 codes were used to determine HIV diagnoses and to identify hospitalizations and procedures for ACS. Multivariable analysis adjusting for age, sex, race, income, hospitalization year, tobacco, alcohol, and substance use and comorbidities was used to compare procedure rates by HIV status, with appropriate weighting to account for the sampling design including stratification and hospital clustering in the NIS. Results: Overall, the dataset included 1,091,759 ACS hospitalizations, 0.35% of which (n=3783) were in HIV-infected patients. HIV-infected patients were more often male (76.6% vs 57.9%), Black (44.4% vs 10.9%), and of lower income status (45.3% vs 30.2% in first quartile of income by zip code) compared to uninfected patients. Overall rates of cardiac catheterization and revascularization (PCI or CABG) were 53.3% and 37.4%, respectively. In multivariable regression, we found that HIV-infected patients were 1) less likely to undergo catheterization (OR 0.68, CI 0.62-0.73), 2) less likely to undergo revascularization with PCI or CABG (OR 0.80, CI 0.73-0.89), and 3) less likely to receive a drug eluting stent (OR 0.74, 0.63-0.86) when PCI was performed. There was no difference in time to catheterization between the two groups. Conclusion: HIV-infected patients are less likely to receive standard catheterization and revascularization procedures after ACS presentation, suggesting disparities in access to care for these patients. In addition, the lower rates of CABG and PCI with DES may impact long-term outcomes for these patients, as these procedures are associated with less frequent need for repeat revascularization. Reasons for lower utilization of CVD procedures in HIV-infected patients warrants further investigation.

Poster and Themed Discussion Abstracts

CROI 2017 261