CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

(ΔTBR), we observed a small but non-significant decrease in TBR in the LDMTX group ((ΔTBR: -0.126 [-0.41, 0.258]) relative to placebo (0.026 [-0.176, 0.438], p=0.47, Fig 1A). Higher than anticipated variability in TBR and lower than planned enrollment limited our ability to detect group differences in TBR. For the secondary endpoint (ΔSUV), we observed a significant between-group difference in the LDMTX group relative to placebo (ΔSUV: -0.034 [-0.311, 0.095] vs. 0.096 [-0.081, 0.313], LDMTX vs placebo, p=0.05, Fig 1B). This represented an approx. 2% decrease in SUV (from baseline 2.01) in the LDMTX, and a 5% increase in SUV (from baseline of 1.82) in the placebo group. Conclusion: LDMTX may reduce arterial inflammation in HIV-infected adults with or at risk for ASCVD, at least as measured by ΔSUV. This finding may explain the apparent beneficial impact of LDMTX on ASCVD risk in chronic inflammatory diseases. The potential effect of LDMTX on arterial inflammation in HIV should be studied in a larger cohort.

between SAT and LpPLA2(ρ=-0.24, P=.05), as well as VAT and LpPLA2(ρ=0.37, P=.002), oxLDL(ρ=0.28, P=.05), and hsCRP (ρ=0.29, P=.002). In separate models simultaneously controlling for VAT, SAT, age, CD4+ count, and viral load among PLWH, reduced SAT was an independent predictor of LpPLA2(P=.006) and increased VAT was an independent predictor of LpPLA2(P=.007) and oxLDL(P=.004). Conclusion: Highly inflamed adipose tissue, in the context of SAT loss and/ or VAT accumulation, may be linked to arterial inflammation. Strategies to reduce lipodystrophy and restore normal adipose biology may have therapeutic benefit to dampen arterial inflammation in the HIV population among whom traditional risk factor modification does not completely mitigate CVD risk. Kathleen V. Fitch 1 , Meghan Feldpausch 1 , Patrick Maehler 1 , Martin Torriani 1 , Gail K. Adler 2 , Steven K. Grinspoon 1 , Suman Srinivasa 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 Brigham and Women’s Hospital, Boston, MA, USA Background: Well-treated persons living with HIV(PLWH) at risk for fat dysfunction demonstrate renin-angiotensin-aldosterone system(RAAS) dysregulation. Natriuretic peptides(NP) are key cardiac hormones which serve as negative regulators on the RAAS and play a role in preserving cardiac structure and metabolic homeostasis. In generalized obesity, relative NP deficiency contributes to advanced metabolic risk. We investigated BNP in relation to aldosterone and body composition for the first time in HIV. Methods: Serum brain natriuretic peptide(BNP) was prospectively assessed during acute activation of the RAAS using a 7-day low sodium diet and controlled posture techniques among 20 PLWH and 10 persons living without HIV(PLWOH) well-phenotyped for body composition. Non-normally distributed variables were log transformed for the analyses(Pearson’s correlation, Student’s t-test, ANOVA); these data are shown as median[IQR] only for clinical interpretation. Results: PLWH(mean age 49±2yrs, duration HIV 18±1yrs, duration ART 11±1yrs, CD4+ count 571±73cells/μL, log VL 1.77±0.19copies/mL) were of similar age, sex, and body composition vs. PLWOH. Log BNP was significantly and inversely related to body composition [waist circumference(r=- 0.46,P=.04), BMI(r=-0.55,P=.01), body adiposity index (r=-0.49,P=.03)], metabolic indices [total cholesterol(r=-0.44,P=.05), HOMA-IR(r=-0.44,P=.05)], and aldosterone(r=-0.49,P=.03) among the HIV group. No significant correlations were demonstrated to BNP among PLWOH. BNP(60[44,152] vs. 196[91,251],P=.04) was significantly lower and aldosterone(13.8[9.7,30.9] vs. 9.2[7.6,13.6]ng/dL,P=.03) higher among PLWH vs. PLWOH. In a four-group comparison stratifying by HIV serostatus and above/below BMI 25(overweight category), BNP decreased significantly across groups, being highest in PLWOH with BMI<25 and lowest in PLWH with BMI≥25(238[77,935], 193[77,206], 125[49,157], 52[31,215]ng/dL in PLWOH/BMI<25, PLWOH/BMI≥25, PLWH/ BMI<25, PLWH/BMI≥25, respectively (overall=.01)). Further stratification among the HIV group into 3 standardized BMI categories, under/normal weight(BMI<25), overweight(25≤BMI<30), and obese(BMI≥30), was also significant for a reduction in BNP across increasing BMI(P=.01). Conclusion: Relative BNP deficiency among PLWH with excess adiposity may contribute to RAAS dysregulation and potentially drive metabolic disease, such as insulin resistance. Novel strategies which block aldosterone and augment BNP may be potentially useful to reduce cardiometabolic risk in HIV.

686 CARDIAC BNP DEFICIENCY RELATES TO EXCESS ADIPOSITY AND METABOLIC PERTURBATIONS IN HIV

Poster Abstracts

685 LIPODYSTROPHY IS AN IMPORTANT DETERMINANT OF MARKERS OF ARTERIAL INFLAMMATION IN HIV Suman Srinivasa , Kathleen V. Fitch, Martin Torriani, Markella V. Zanni, Patrick Maehler, Sara E. Looby, Janet Lo, Steven K. Grinspoon Massachusetts General Hospital, Boston, MA, USA Background: Persons living with HIV(PLWH) well-treated on antiretroviral therapies remain at risk for ensuing arterial inflammation. The exact mechanism for inflammatory-mediated cardiovascular disease (CVD) in HIV remains unclear. HIV lipodystrophy has been associated with advanced metabolic disease. In this regard, visceral adipose tissue (VAT) accumulation and subcutaneous adipose tissue (SAT) loss contribute to a unique and highly inflamed adipose depot. Therefore, we sought to investigate the relationship between adipose depots and specific markers of arterial inflammation to gain insight into the potential link between lipodystrophy and CVD risk. Methods: 155 PLWH and 71 individuals without HIV(PLWOH) and no known CVD were previously recruited and well-phenotyped for body composition. VAT and SAT were assessed via single slice CT abdomen imaging. Circulating markers of arterial inflammation [lipoprotein-associated phospholipase A2(LpPLA2), oxidized LDL(oxLDL), high sensitivity troponin T(hsTnT), high sensitivity C reactive protein(hsCRP)] were evaluated. Relationships were assessed by Spearman’s correlation. Results: PLWH(mean age 47±1yrs, duration HIV 14±1yrs, duration ART 8±0yrs, CD4+ count 552±24cells/μL, logVL 1.82±0.04copies/mL) were of similar age and sex vs. PLWOH. Despite similar BMI and VAT, PLWH(199[126,288] vs. 239[148,358]cm2,P=.04) had significantly lower SAT compared to PLWOH. Reduced SAT was inversely correlated with LpPLA2(ρ=-0.19, P=.02) and hsTNT(ρ=-0.24, P=.004) among PLWH. Furthermore, increased VAT was significantly and positively related to LpPLA2(ρ=0.25, P=.003), oxLDL(ρ=0.28, P=.0005), hsTNT(ρ=0.28, P=.0007), and hsCRP (ρ=0.32, P=<.0001) among the HIV group. Similar analyses among PLWOH revealed significant relationships

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