CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

655 ENDOTHELIAL DYSFUNCTION IS COMMON IN EARLY HIV INFECTION AND IS REVERSIBLE WITH ART Kelvin Bush, Julie Teel, James Watts, Gadiel Alvarado, Rosco Gore, Jason Okulicz San Antonio Military Medical Center, San Antonio, TX, USA Background: Endothelial dysfunction is an important mechanism for cardiovascular diseases (CVD); however, the prevalence of endothelial dysfunction during early HIV infection and its reversibility with early antiretroviral therapy (ART) is unknown. Endothelial dysfunction can be reliably assessed by noninvasive measurement of peripheral arterial tonometry using the reactive hyperemia index (RHI). We evaluated RHI in ART-naïve early HIV seroconverters and after early ART. Methods: RHI determinations (using EndoPAT 2000) were made in US Air Force members diagnosed with HIV infection between September 1, 2015 and September 30, 2017 (n=61); ART was initiated immediately after RHI testing. Log-transformed RHI values of <0.51 and ≥0.51 were defined as abnormal or normal, respectively. A subgroup of patients (n=41) had repeat RHI assessments 6.44 (IQR, 5.98-7.82) months after diagnosis. Results: Patients were mostly younger males (males, 95.1%; African American, 57.4%; median age at diagnosis 27 years) enrolled on average within 12 months of the estimated date of seroconversion; they had fewer CVD risk factors and relatively preserved CD4+ counts (approximately 500 cells/mm3) (Table). At HIV diagnosis, 14 (23.0%) had an abnormal RHI. Age (per 10 year increase) was associated with an abnormal RHI (odds ratio=2.15; P=0.089) while other demographic features, CVD profiles, or HIV disease characteristics were not significant. Forty patients received integrase inhibitor-based regimens; one patient declined ART. Early ART was associated with a significant increase in RHI (n=40; mean (±SD) increase of 0.13 (±0.33; P=0.021); the mean (±SD) increase in RHI was greater in those with an abnormal compared with normal RHI at HIV diagnosis (0.33 [±0.34] vs 0.05 [±0.30]; P=0.03). Of the 11 persons with an abnormal RHI at diagnosis and a follow-up RHI assessment, 8 (72.7%) had normalized RHI. The patient who declined ART converted from a normal (0.60) to abnormal (0.11) RHI after 8.3 months of follow-up. Conclusion: In young, recent HIV seroconverters with low CVD risk, nearly 25% had endothelial dysfunction by RHI assessment. Endothelial dysfunction could not be attributed to HIV disease characteristics (i.e., low CD4, high viral load). Endothelial dysfunction was reversible with early ART in the majority of patients. Conceivably, persistent endothelial dysfunction and associated CVD complications during HIV infection may relate to delayed ART.

Methods: This is a cross-sectional study involving 90 individuals (68 HIV+ and 22 healthy controls matched by age and sex). AGEs levels were assessed using three different modalities: five different AGEs were measured in the serum; skin AGEs were determined with a non-invasive reader; dietary AGEs were estimated using 24-hour dietary recalls. Markers of inflammation, immune activation, and endothelial dysfunction (by pulse wave velocity and peripheral arterial tonometry) were also measured. Classical t-test and chi-square tests were used to compare AGEs between groups. Spearman correlations were used to explore relationships between variables and were then assessed while adjusting for demographics, BMI, CD4, and viral load. Results: Overall, 71%were male, 68%were African American, with a mean age of 53 years. Among HIV-infected individuals, all participants were on ART by design and most participants (78%) had an undetectable HIV-1 RNA level (≤20 copies/ml). Skin and serum AGEs were significantly higher in HIV-infected participants compared to uninfected controls (p<0.01), while no differences in dietary AGEs were found between groups(p=0.2). In the HIV-infected group, but not in controls, skin and circulating AGEs were significantly associated with inflammatory and oxidative markers, and with endothelial dyfunction (table). These associations remained significant after adjusting for clinically relevant factors. Conclusion: For the first time, we found higher levels of serum and skin AGE despite similar dietary AGE, in HIV infected individuals, suggesting intrinsic producton of AGE. The relationship between serum/skin AGE and inflammatory, oxidative and cardiovascular markers highlight the potential implications of AGEs in chronic inflammation, oxidative stress, and endothelial dysfunction in HIV, suggesting a new potential target for HIV-associated heightened inflammation and cardiovascular risk.

Poster Abstracts

657 CUMULATIVE ART EXPOSURE IS ASSOCIATED WITH ENDOTHELIAL AND IMMUNE ACTIVATION IN HIV Jose R. Castillo-Mancilla 1 , Samantha MaWhinney 2 , Ryan P. Coyle 1 , James Morrison 1 , Eric Poeschla 1 , Rick Rapaport 1 , Thomas Campbell 1 , Lucas Ellison 1 , Jia-Hua Zheng 1 , Lane R. Bushman 1 , Jennifer J. Kiser 1 , Peter L. Anderson 1 , Jonathan Z. Li 3 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 Colorado School of Public Health, Aurora, CO, USA, 3 Brigham and Women’s Hospital, Boston, MA, USA Background: Immune activation and inflammation persist in people living with HIV (PLWH) despite ART-mediated HIV suppression. Whether ART exposure is associated with residual inflammation remains unclear. We aimed to assess the association of cumulative ART exposure, quantified using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), with biomarkers of inflammation and immune activation in chronically-treated PLWH with viral suppression. Methods: DBS and plasma were collected at two time points (6 months apart) in PLWH taking a tenofovir disoproxil fumarate (TDF)-based regimen

656 ADVANCED GLYCATION END PRODUCTS, INFLAMMATION, AND ENDOTHELIAL DYSFUNCTION IN HIV Vanessa El Kamari 1 , Alicia Thomas 2 , Abdus Sattar 1 , Grace A. McComsey 2 1 Case Western Reserve University, Cleveland, OH, USA, 2 University Hospitals Cleveland Medical Center, Cleveland, OH, USA Background: HIV-infected individuals are at an increased risk of premature aging and comorbidities. The mechanisms underlying these complications remain poorly understood. Advanced glycation end products (AGEs) are produced with aging and are increased in inflammatory and oxidative stress conditions. Elevated AGEs are associated with the progression of different pathological conditions such as diabetes and renal diseases. Their role in HIV remains unknown.

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