Abacavir antiretroviral therapy and indices of subclinical vascular disease in persons with HIV.

Claudia A Martinez,Alex Gonzalez,Meela Parker,Mollie S Pester,Barry E Hurwitz,Ivonne H Schulman,Jeffrey K Raines,Armando Mendez,Rishi Rikhi,Maria L Alcaide,Michael A Kolber,Michaela Larson,Jennifer Chavez,Huimin Yan

doi:10.1371/journal.pone.0264445

Claudia A Martinez, Alex Gonzalez + Show 12 more

Open Access

https://doi.org/10.1371/journal.pone.0264445

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Journal: PloS one	Publication Date: Mar 10, 2022
Citations: 2	License type: CC BY 4.0

Affiliation: University of Miami, Wake Forest University

Abstract

Indices of cardiovascular disease (CVD) risk, vascular endothelial dilation, arterial stiffness and endothelial repair were examined in persons with HIV (PWH) on an antiretroviral therapy (ART) that included abacavir (ABC+) in comparison with PWH on ART without abacavir (ABC-), and with HIV seronegative (HIV-) individuals. The 115 participants (63% men), aged 30-50 years, did not have CVD, metabolic, endocrine, or chronic renal conditions. PWH were on stable ART for six-months or more. Vascular assessments included flow-mediated dilation (FMD), aortic, radial and femoral arterial stiffness (cAIx, crPWV, cfPWV), and thigh and calf arterial compliance (Vmax50). Endothelial repair was indexed by endothelial progenitor cell colony forming units (EPC-CFU). Traditional CVD risk measures included blood pressure, central adiposity, lipids, insulin resistance (HOMA-IR), CRP and ASCVD score. Analyses controlled for demographics (age, sex, education), medications (antihypertensive, statin/fibrate, antipsychotic), and substance abuse (ASSIST). No group differences were observed in central adiposity, HOMA-IR, CRP, or ASCVD risk score. However, the ABC- group displayed greater dyslipidemia. The ABC+ group displayed no difference on FMD, cAIx, cfPWV or calf Vmax50 compared with other groups. When CD4 count and viral load were controlled, no additional differences between the ABC+ and ABC- groups emerged. Analyses of crPWV and thigh Vmax50 suggested supported by a trend toward lower EPC-CFU in the HIV+ groups than the HIV- group. Findings indicate that ABC treatment of 30-50 year-old PWH on stable ART is not likely to contribute in a robust way to higher CVD risk.

Highlights

Persons living with HIV (PWH) have elevated subclinical cardiometabolic complications and have a 1.5-2-fold higher incidence of cardiovascular disease (CVD) compared with seronegative counterparts [1, 2]
No group differences were observed in central adiposity, HOMA-IR, Creactive protein (CRP), or atherosclerotic cardiovascular disease risk (ASCVD) risk score
The ABC+ group displayed no difference on flow-mediated dilation (FMD), central augmentation index (cAIx), cfPWV or calf Vmax50 compared with other groups

Summary

Introduction

Persons living with HIV (PWH) have elevated subclinical cardiometabolic complications and have a 1.5-2-fold higher incidence of cardiovascular disease (CVD) compared with seronegative counterparts [1, 2]. HIV infection promotes immune activation and increases oxidative stress causing vascular endothelial dysfunction and decreased endothelium repair leading to premature vascular dysfunction and subclinical CVD pathophysiology [6–8]. Subclinical vascular pathogenesis may be detected using measures of vascular endothelial dysfunction, indexed by impaired flow-mediated dilation (FMD) measured by ultrasound imaging of the brachial artery [9]. Elevated arterial stiffness (i.e., reduced arterial compliance), estimated using peripheral artery tonometry and other cuff-based oscillometric methods, are predictively associated with increased CVD pathophysiology and events [10–13]. The presence of vascular disease, as indexed by lower numbers of endothelial progenitor cells colony forming units (EPC-CFU), is a marker of impaired endothelial repair and CVD morbidity and mortality [14, 15]

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