CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

759 Unique Circulating MicroRNA Profiles and Endothelial Function in HIV Infection Venkata A. Narla 1 ; Nirav Bhakta 2 ; Jane E. Freedman 3 ; KahramanTanriverdi 3 ; Kristinalisa Maka 1 ; Steven Deeks 2 ; Peter Ganz 1 ; Priscilla Hsue 1 1 San Francisco General Hospital, University of California San Francisco, San Francisco, CA, US; 2 University of California San Francisco, San Francisco, CA, US; 3 University of Massachusetts Medical School, Worcester, MA, US Background: MicroRNAs (miRs) are non-coding RNAs that regulate gene expression and can serve as biomarkers given their stability in blood and characteristic expression in various diseases. The role of extracellular miRs as potential biomarkers in HIV infection and HIV-associated cardiovascular disease (CVD) has not been described. Methods: We analyzed the expression of 192 plasma-derived miRs from 69 HIV-infected individuals and 24 uninfected controls using Taqman miR Expression Assays and a high throughput RT-PCR instrument (Fluidigm). We also examined the association between 68 circulating miRs and flow-mediated dilatation of the brachial artery (FMD), a physiologic measure of endothelial function and a strong predictor of future CVD events, using Firefly Bioworks hydrogel particles-based miR assays. Comparisons were made using Student’s t-test, Wilcoxon rank-sum test, ANOVA, and Kruskal-Wallis test where appropriate, and false discovery rate was applied. Results: HIV–infected individuals and controls were matched in age, gender, and traditional risk factors. The median age was 46 years (IQR 40 to 54) and 91%were men. Among the HIV patients, 72.5%were on antiretroviral therapy and 64% had an undetectable viral load. Twenty-nine miRs were differentially expressed in the plasma of HIV-infected individuals compared to controls (p<0.05 and FDR <0.15). In particular, miRs-29c, 146b, 223, and 382 have reported intracellular roles in HIV latency, and miRs-126, 145, and let-7 have been shown to be differentially expressed in coronary artery disease (CAD) among individuals without HIV. Levels of miRs-34a, 27b, and 1183 varied with different FMD quartiles (p<0.05). Thirty-eight miRs were differentially expressed in the serum of HIV-infected individuals from the low FMD quartile compared with the top FMD quartile (p<0.05; thirty miRs had FDR<0.05 and eight miRs had FDR< 0.07). In this profile, in particular, miRs-1, 133a, 133b, 208a, 208b, 499, 145, and 155 have been shown to be differentially expressed in CAD patients without HIV. Conclusions: We demonstrate a unique miR expression profile of 29 miRs in HIV-infected individuals, as well as a unique profile of 38 miRs in HIV-infected individuals with high CVD risk and impaired endothelial function. These miR profiles may be useful in identifying HIV-infected individuals who are at increased risk for CVD, may help elucidate the underlying mechanism of HIV-associated CAD, and may be therapeutic targets for new anti-HIV drugs and CVD drugs. 760 Cerebral Vasoreactivity Is Impaired in Virally Suppressed HIV-Infected Individuals Background: Rates of vascular outcomes, including stroke, are higher in HIV-infected individuals than in age-matched uninfected controls. Endothelial dysfunction and accelerated atherosclerosis related to chronic inflammation and immune activation may contribute to HIV-associated cardiovascular risk. The mechanisms underlying increased cerebrovascular risk in HIV infection have not been investigated. We compared cerebral vasoreactivity (VR), a measure of intracranial endothelial function associated with cerebrovascular injury, by HIV status. We also evaluated the effect of HIV-specific factors on cerebral VR. Methods: Cross-sectional study of bilateral cerebral VR, assessed using the transcranial Doppler carbon dioxide (CO 2 ) challenge test, in HIV-infected participants and uninfected controls recruited from SCOPE (Study of the Consequences of the Protease Inhibitor Era). All HIV-infected participants were on a stable antiretroviral therapy (ART) regimen for at least 24 weeks with undetectable plasma HIV RNA level. Cerebral VR was defined as the percentage change in mean flow velocity per unit change in end-tidal CO2. We used mixed effects multivariate linear regression models adjusted for age, race and clinically relevant variables chosen by forward stepwise regression to determine the association between HIV and cerebral VR and between HIV-specific factors and cerebral VR. We included a random person effect to account for within-person correlation of bilateral measurements. Results: 65 HIV-infected and 28 uninfected control participants matched by age and sex were studied. Median age was 57 years, 96%were men and 28%were non-white race. Mean duration of HIV infection was 20 years. Diabetes mellitus (12 vs. 0%, p=0.052), aspirin (49 vs. 21%, p=0.012), statin (48 vs. 11%, p=0.001) and marijuana use (48 vs. 21%, p=0.018) were more prevalent among HIV-infected participants than uninfected controls. In a multivariate model, HIV infection, non-white race and select traditional vascular risk factors were associated with worsened cerebral VR (Table). Among HIV-infected individuals, we did not find a statistically significant effect of recent or nadir CD4 count, duration of HIV infection or ART class on cerebral VR. Felicia C. Chow 1 ; Claire Mills 1 ; Nerissa Ko 1 ; Courtney Carroll 1 ; Richard Price 1 ; Steven Deeks 1 ; Farzaneh A. Sorond 2 ; PriscillaY. Hsue 1 1 University of California San Francisco, San Francisco, CA, US; 2 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, US

Poster Abstracts

Conclusions: Treated and virally suppressed HIV infection is an independent risk factor for impaired cerebral VR, a marker of subclinical cerebrovascular dysfunction. Further investigation into the etiology of cerebrovascular injury in chronic, well-controlled HIV infection is merited.

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CROI 2015