Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment.

Abstract

BACKGROUND:

Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART).

METHODS:

In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound.

RESULTS:

Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-α (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), monocyte chemoattractant protein 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. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-α levels remained elevated compared with HIV-uninfected 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 carotid artery intima-media thickness.

CONCLUSIONS:

Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-α), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. 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-infected patients, even with effective therapy.

• Authors: Robert C Kaplan, Alan L Landay, Howard N Hodis, Stephen J Gange, Philip J Norris, Mary Young, Kathryn Anastos, Phyllis C Tien, Xiaonan Xue, Jason Lazar, Christina M Parrinello, Lorie Benning, Russell P Tracy
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 60 Issue 4 Pg. 359-68 (Aug 01 2012) ISSN: 1944-7884 [Electronic] United States
• PMID: 22592585 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Retroviral Agents
• Biomarkers
• Cytokines
• Fibrin Fibrinogen Degradation Products
• fibrin fragment D
• Fibrinogen

Topics

• Adult
• Anti-Retroviral Agents (administration & dosage)
• Atherosclerosis (diagnosis, epidemiology)
• Biomarkers (blood)
• Carotid Arteries (diagnostic imaging, pathology)
• Cytokines (blood)
• Female
• Fibrin Fibrinogen Degradation Products (analysis)
• Fibrinogen (analysis)
• HIV Infections (complications, drug therapy)
• Humans
• Prevalence
• Tunica Intima (diagnostic imaging, pathology)
• Ultrasonography