Potential Atherogenic Biomarkers among HIV+ Women Initiating ART
Christina Parrinello*1, A Landay2, H Hodis3, P Norris4, K Anastos1, P Tien4,5, X Xue1, L Benning6, R Tracy7, and R Kaplan1
1Albert Einstein Coll of Med, Bronx, NY, US; 2Rush Univ Med Ctr, Chicago, IL, US; 3Univ of Southern California, Los Angeles, US; 4Univ of California, San Francisco, US; 5San Francisco VAMC, CA, US; 6Johns Hopkins Univ Bloomberg Sch of Publ Hlth, Baltimore, MD, US; and 7Univ of Vermont Coll of Med, Burlington, US
Background: Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV+ adults before and after beginning HAART.
Methods: In the Women’s Interagency HIV Study (WIHS), 127 HIV+ women studied pre- and post-HAART were propensity score-matched to HIV– controls. We obtained 6 semi-annual measurements of soluble CD14, tumor necrosis factor (TNF)-a, soluble interleukin (IL)-2 receptor, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, D-dimer, and fibrinogen. Carotid artery intima-media thickness (cIMT) was measured by B-mode ultrasound.
Results: Relative to HIV– controls, HAART-naïve HIV+ women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank p <0.0001), TNF-a (6.3 vs 3.4 pg/mL, p <0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, p <0.0001), IL-10 (3.3 vs 1.9 pg/mL, p <0.0001), MCP-1 (190 vs 163 pg/mL, p <0.0001), and D-dimer (0.43 vs 0.31 µg/mL, p <0.01). Elevated biomarker levels declined after HAART. While most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-a levels remained elevated compared to HIV– women (+0.8 pg/mL, p = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (p = 0.02), IL-6 (p = 0.05), and D-dimer (p = 0.03) were associated with increased cIMT.
Conclusions: Untreated HIV infection is associated with abnormal hemostasis (e.g., D-dimer), and pro-atherogenic (e.g., TNF-a) and anti-atherogenic (e.g., IL-10) inflammatory markers. HAART reduces most inflammatory mediators to levels found in HIV– women. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV+ patients, even with effective therapy.