CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Conclusions: HIV-infected women with reduced ovarian reserve have increased subclinical coronary plaque compared with premenopausal women in whom AMH is measurable. This relationship holds when controlling for CVD risk factors (including age) and immune activation. Our findings demonstrate that reduced ovarian reserve may contribute to CVD burden in HIV-infected women and support a comprehensive assessment of CVD risk prior to completion of menopause in this population. Future work applying our reproductive aging classification paradigmwill explore mechanisms through which reproductive aging influences immune activation, plaque, and overall CVD risk among women aging with HIV.

Figure 1. Reproductive Aging Classification Scheme

PREMENOPAUSAL

POSTMENOPAUSAL

MENSTRUAL HISTORY

Menses within the past 12 months

No menses within the past 12 months

ANTIMULLERIAN HORMONE LEVELS (AMH)

Detectable AMH; variable by age Group 1: Premenopausal with measurable AMH

Undetectable AMH

Undetectable AMH

Group 3: Postmenopausal

Group 2: Premenopausal with reduced ovarian reserve

651 Correlates and Longitudinal Implications of FGF23 Levels in HIV-Positive Individuals

Mohamed G. Atta 1 ; Michelle Estrella 2 ; Derek M. Fine 1 ; Katie Zook 1 ; Jose Manuel MonroyTrujillo 2 ; James H. Stein 3 ; Gregory M. Lucas 1 1 Johns Hopkins Univ, Baltimore, MD, USA; 2 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA; 3 Univ of Wisconsin-Madison, Madison, WI, USA

Background: High plasma concentrations of fibroblast growth factor-23 (FGF23), which is crucial in phosphorus homeostasis, is an early marker of kidney dysfunction and has been associated with increased cardiovascular disease mortality. HIV-positive persons are at increased risk for cardiovascular and kidney disease, but there are few data assessing the role of FGF23 in these conditions in HIV-positive individuals. Methods: We measured intact plasma FGF23 in a cohort of 100 HIV-negative and 191 HIV-positive, non-diabetic adults with normal estimated kidney function. We measured glomerular filtration rate by iohexol disappearance from plasma (iGFR) annually, albumin-creatinine ratio (ACR) every 6 months, and assessed for carotid plaque and measured carotid intima-media thickness (IMT) at baseline and at 2 years. Progressive albuminuria was defined as a follow-up ACR that was ≥2-fold higher than baseline and ≥30 mg/g. We log-transformed FGF23 levels in simple and hierarchical regression models to assess associations with baseline factors and with longitudinal changes in disease markers. Results: The cohort was 29% female, 93% black, with a median age of 49 years, and 46%were infected with hepatitis C virus (HCV). FGF23 levels were similar in HIV-negative and HIV-positive subjects (median 8.9 vs. 8.4 pg/mL, P=0.53). Among HIV-positive subjects, factors independently associated with higher FGF23 levels at baseline included being female (adjusted ratio of geometric means [95% CI], 1.38 [1.13, 1.69]), serum phosphorus (1.21 [1.03, 1.42], HCV coinfection (1.26 [1.04, 1.53]), and non-suppressed HIV RNA (1.33 [1.00, 1.76]). In cross-sectional baseline analysis of HIV-positive subjects (adjusted for demographic and cardiovascular risk factors including smoking, hypertension, and hyperlipidemia) FGF23 was not significantly associated with iGFR, albuminuria, presence of carotid plaque, or carotid IMT. However, adjusted for the same factors, higher baseline FGF23 was associated with a more rapid increase in internal carotid artery IMT (13 µm/year, 95% CI, 3, 24) and risk of progressive albuminuria (odds ratio 1.95 [95% CI]: 1.33, 2.87). Conclusions: FGF23 levels in HIV-positive subjects were significantly higher in women, HCV-coinfected persons and in those with unsuppressed HIV RNA levels. Higher FGF23 levels at baseline were associated with more rapid carotid IMT progression and with progressive albuminuria. Together, these factors suggest a role for FGF23 in cardiovascular and kidney disease in HIV-positive populations. 652 Nonclassical Monocyte, MCP-1 Predict Subclinical Atherosclerosis Progression in HIV Dominic C. Chow 1 ; Lishomwa C. Ndhlovu 1 ; Lindsay M. Kohorn 1 ; Guangxiang Zhang 1 ; Howard N. Hodis 2 ; Matthew Budoff 3 ;Yanjie Li 2 ; Sheila M. Keating 4 ; Philip J. Norris 4 ; Cecilia M. Shikuma 1 1 Univ of Hawaii, Honolulu, HI, USA; 2 Univ of Southern California, Los Angeles, CA, USA; 3 Harbor-Univ of California Los Angeles Med Cntr, Torrance, CA, USA; 4 Blood Systems Rsr Inst, San Francisco, CA, USA Background: Persistent inflammation and immune dysregulation can contribute to cardiovascular disease (CVD) risk in patients with chronic HIV infection. Methods: We conducted a longitudinal analysis utilizing HIV-infected subjects on stable antiretroviral therapy (ART) in the Hawaii Aging with HIV-Cardiovascular (HAHC-CVD) study to determine the correlation of peripheral monocyte subsets and biomarkers of inflammation to progression of atherosclerosis using 2 year change in carotid artery intima-

Poster Abstracts

media thickness (CIMT) and coronary artery calcium (CAC). Peripheral blood mononuclear cells (PBMC) were immunophenotyped by multiparametric flow cytometry to quantify classical (CD14 ++ CD16 - ), intermediate (CD14 ++ CD16 + ), non-classical (CD14 low/+ CD16 ++ ) and transitional (CD14 + CD16 - ) monocyte subsets. Biomarkers (sE-selectin, sVCAM-1, sICAM-1, MMP-9, tPA-1, hsCRP, IL-6, IL-8, IL-10, TNF-α, MCP-1, IFN-α) were assessed by multiplex Luminex assay. The primary outcome variables were change in CIMT (right common carotid artery (CCA) and bifurcation (BIF)) and CAC over 2 years. Results: 105 subjects: 91%male, median age 51 (Q1, Q3; 47, 57) years, median CD4 count 491 (352, 660) cells/mm 3 , and 87%with HIV RNA<50 copies/mL. The rate of change in CCA, BIF, and CAC was 0.010 mm/year, 0.0097 mm/year, and 16.2 Agatston units/year, respectively. Change in CCA correlated with TNFα (r= - 0.28, p=0.026) but not with any monocyte subset. Change in BIF correlated with non-classical monocytes (r=0.29, p=0.038) and MCP-1 (r=0.34, p=0.005). Change in CAC correlated with non-classical monocytes (r=0.27, p=0.015) and MCP-1 (r=0.46, p<0.001). Non-classical monocyte and MCP-1

remained significantly associated with CAC and BIF progression after adjustment for age, hypertension, diabetes mellitus, total/HDL cholesterol ratio, and smoking history. Conclusions: Non-classical monocytes and MCP-1 were associated with progression of atherosclerosis. The role of monocyte subsets in atherosclerosis warrants further investigation.

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