PB1304 - Characterising Endothelial Colony-Forming Cells in The Context Of HIV: People Living with HIV Have Elevated Endothelial Colony-Forming Cell Frequency

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Akif A. Khawaja, PhD

Research Associate
Imperial College London
London, England, United Kingdom

Co-Author(s)

RM

Robert T. Maughan

Research Associate
National Heart and Lung Institute, Imperial College London
London, England, United Kingdom
Koralia Paschalaki, MD, PhD

Respiratory physician - Clinical Research Fellow
National Heart and Lung Institute, Imperial College London
London, England, United Kingdom
CP

Charis Pericleous

Research Fellow
National Heart and Lung Institute, Imperial College London
London, England, United Kingdom
JM

Justin C. Mason

Professor of Vascular Rheumatology
National Heart and Lung Institute, Imperial College London
London, England, United Kingdom
MN

Mark Nelson

Consultant Physician
Chelsea and Westminster Hospital NHS Foundation Trust
London, England, United Kingdom
GT

Graham P. Taylor

Professor of Human Retrovirology
Department of Infectious Disease, Imperial College London
London, England, United Kingdom
Anna M. Randi, MD,PhD

Professor of Cardiovascular Medicine
Imperial College London
London, England, United Kingdom
MB

Marta Boffito

Consultant Physician
Chelsea and Westminster Hospital NHS Foundation Trust
London, England, United Kingdom
ME

Michael Emerson

Reader in Platelet Pharmacology
National Heart and Lung Institute, Imperial College London
London, England, United Kingdom

Background: Improvements in HIV management have transformed a once fatal infection into a manageable chronic condition, resulting in an ageing population of people living with HIV (PLHIV). PLHIV are less likely to die from AIDS-related illness, but are twice as likely to develop cardiovascular disease (CVD). Patient-derived endothelial colony-forming cells (ECFCs) are being increasingly used to study endotheliopathy of specific diseases, but have not been exploited within the context of HIV where the pathophysiology of CVD remains unclear.

Aims: To assess whether ECFC can be successfully isolated from PLHIV.

Methods: Whole blood was obtained from PLHIV on effective antiretroviral therapy (ART) (n=10) or HIV-negative people accessing Pre-Exposure Prophylaxis (PrEP, n=10). Peripheral blood mononuclear cells (PBMCs) were isolated and monitored for ECFC growth. Day of colony emergence, time to first split (P0 split), and ECFC frequency were used to define isolation kinetics. A previously isolated HIV-negative, ART-naïve control group was used as a reference control group. Statistical significance was determined by one-way ANOVA with Tukey's multiple comparison test.

Results: ECFCs emerged in 10/10 PLHIV, 8/10 PrEP users and 12/13 controls. From the first colony emerging, PLHIV-ECFCs took 22.5±1.5 days (mean ±SEM) for colonies to establish for first split, which was significantly longer than both PrEP-ECFCs (15.4±2.1 days, p< 0.05) and reference ECFCs (14.9±1.1 days, p< 0.01). PLHIV had higher ECFC frequencies (0.52±0.15 colonies/1x10^6 PBCMs) compared to both the PrEP group (0.21±0.06 colonies/1x10^6 PBCMs, p< 0.05) and reference control group (0.13±0.03 colonies/1x10^6 PBCMs, p< 0.01).

Conclusion(s): ECFCs from PLHIV on effective therapy can be isolated and will be used to explore the molecular effects of ART and HIV infection upon endothelial thrombo-inflammatory properties. The significance of higher ECFC frequency and the longer time for colony establishment in PLHIV is currently unknown, but may provide a route to defining, preventing and treating endothelial dysfunction in this population.