CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

and the binding of fibrinogen to the activated αIIbβ3 integrin upon ex vivo stimulation of whole blood with three different platelet agonists (ADP, collagen-related-peptide and thrombin receptor activator peptide). Plasma markers of platelet activation (platelet factor-4, beta-thromboglobulin and P-selectin) and inflammation (high-sensitive C-reactive protein (hs-CRP) were also measured. Analysis was based on intention-to-treat using an unpaired t-test or Mann-Whitney test. Clinicaltrials.gov identifier: NCT02383355. Results: The groups were well matched. Overall, 95% of participants were male with a median age of 48yrs, and a median CD4 count of 660 cells/µL. No Grade III-IV adverse events were recorded. At 3 months, the Δ platelet reactivity, to all three platelet agonists, were similar between the two groups. Neither PMA formation nor plasma levels of platelet factor-4, beta-thromboglobulin and soluble P-selectin were different between groups. In addition, plasma hsCRP did not differ between treatments at 3 months. Conclusion: A switch to a raltegravir-based regimen in virally suppressed HIV-infected individuals reduces neither platelet reactivity nor platelet-monocyte aggregation. 611 Background: Atherosclerotic cardiovascular disease (ACVD) is among the leading causes of non-AIDS-related comorbidity and mortality in HIV+ individuals on potent antiretroviral therapy (ART). High-density lipoprotein (HDL), an acceptor of lipid exported frommonocytes/macrophage, is functionally altered in HIV+ individuals, possibly due to increased oxidation, which may lead to impaired cholesterol accepting abilities. However, the effect of HIV-1-related altered HDL function on the generation of lipid-laden macrophage associated with atherosclerotic disease progression known as foam cells is unclear. Methods: The function of HDLs isolated from the plasma of HIV- (n=5) or HIV+ (n=10) individuals (HIV-HDL) was measured by two established independent cell free assays: assay A (measured lipid peroxidation and antioxidant function) and assay B (measured rate of apoA-I exchange). The foam cell forming ability of native HDL, HIV-HDL or commercial HDL oxidized in vitro (Cu2+ or 13(3)-HPODE; HDLox) was measured using an established in vitro model of monocyte transendothelial migration and foam cell formation where monocytes exposed to HDLs migrate across a TNF-activated endothelial monolayer into a collagen matrix. Following migration and culture, monocyte-derived foam cells were counted by microscopy. Results: HIV+ individuals had a median age of 42 (range 35-46 years), median CD4 count 550 cells/mm3, viral load <50 copies/ml and were all on efavirenz/emtricitabine/ tenofovir DF. All participants had low risk for CVD and no history of dyslipidemia or statin use. HIV-HDL had reduced antioxidant function and rate of apoA-I exchange, indicative of dysfunction, than native HDL from HIV- individuals (P<0.05 for both assays). Dysfunctional HIV-HDL promoted monocyte-derived foam cell formation more than HDLs isolated frommatched HIV- individuals (33.0% vs 26.2% foam cells, respectively; P<0.01). In vitro HDLox gave similar results compared to unoxidised HDL (P<0.05 for both). Conclusion: Dysfunctional HDLs isolated from HIV+ individuals on potent ART promote monocyte-derived foam cell formation in an in vitro model of atherosclerosis. Foam cell formation was enhanced when monocytes were exposed to artificially oxidised HDL, implicating a role for oxidised HDL in enhanced foam cell formation in HIV+ individuals. These data provide important mechanistic insight into the role of dysfunctional HDLs as possible drivers of increased atherosclerotic risk in this population. DYSFUNCTIONAL HDL FROM HIV+ INDIVIDUALS PROMOTES FOAM-CELL FORMATION IN VITRO Thomas A. Angelovich 1 , Anna Hearps 1 , Margaret D. Shi 1 , Theodoros Kelesidis 2 , Anthony Jaworowski 1 1 Burnet Inst, Melbourne, Australia, 2 Univ of California Los Angeles, Los Angeles, CA, USA

Poster and Themed Discussion Abstracts

612 HDL CHOLESTEROL EFFLUX CAPACITY IS INVERSELY RELATED TO CLASSICAL MONOCYTE NUMBER Santhosh R. Mannem 1 , Dominic Chow 1 , Martin Playford Playford 2 , Beau K. Nakamoto 1 , Kalpana J. Kallianpur 1 , Mary Margaret Byron 1 , Brooks I. Mitchell 1 , Cecilia Shikuma 1 , Nehal N. Mehta 2 1 Univ of Hawaii, Honolulu, HI, USA, 2 Natl Heart, Lung and Blood Inst, Bethesda, MD, USA Background: HIV represents a chronic inflammatory state with increased incidence of cardiovascular disease (CVD). Circulating monocytes are thought to play a role in CVD. High- density lipoprotein (HDL) cholesterol efflux capacity provides dynamic function of HDL and several studies showed that HDL cholesterol efflux capacity is correlated strongly with cardiovascular risk. Reverse HDL cholesterol transport frommacrophages/monocytes may be inhibited by HIV which may contribute to increased CVD. Our current study evaluates the relationship between HDL cholesterol efflux capacity and monocyte subsets. Methods: Longitudinal analysis performed on HIV participants on stable antiretroviral therapy > 3 months enrolled in the Hawaii Aging with HIV Cardiovascular Study. Baseline HDL cholesterol efflux capacity and monocyte subsets were measured and defined by differential expression of CD14 and CD16 determined monocyte subsets: classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+/low CD16++) respectively. Simple and multivariable analyses to evaluate the relationship between HDL cholesterol efflux capacity and monocyte subsets were performed. Results: Our study included 116 patients with median age of 50 years of which 86% are male with median CD4 count of 490 cells/mm3, and a majority with undetectable viral load (86%). The HDL cholesterol efflux capacity was negatively associated with classical monocyte number (beta -0.21, P=0.02) even after adjusting for traditional cardiovascular risk factors, demographics, HIV viral load and body mass index. There were no significant associations between HDL cholesterol efflux capacity and other monocyte subsets. Conclusion: HDL cholesterol efflux capacity is inversely associated with classical monocyte number and may suggest an involvement in pro-inflammation and cardiovascular disease in HIV patients. Our findings might suggest that increasing or restoring HDL cholesterol functionality could be an attractive means to modulate monocyte subset distribution and influence monocyte subset counts in CVD. 613 EFFECT OF ART INITIATION ON MONOCYTE AND HDL FUNCTION Jane A. O’Halloran 1 , Theodoros Kelesidis 2 , Luke O’Brien 1 , Therese Herlihy 3 , Louise Rainford 3 , John Lambert 4 , Gerard Sheehan 4 , Niall Mahon 4 , Leo Lawler 4 , Patrick W. Mallon 3

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