We evaluated the changes in the levels of soluble biomarkers of inflammation and coagulation and T-cell activation among participants of AIDS Clinical Trials Group Study A5217 who were started on antiretroviral therapy (ART) within the first 6 months of HIV infection.
Cryopreserved specimens were obtained pre-ART (week 0), at the time of virologic suppression (week 36), and at 36 weeks after treatment interruption (week 72). Levels of D-dimer, C-reactive protein (CRP), and soluble CD14 (sCD14) were measured in plasma, whereas T-cell activation levels, defined as the frequencies of CD4+ and CD8+ T cells coexpressing HLA-DR and CD38, were measured in peripheral blood mononuclear cells.
D-dimer levels were significantly lower at viral suppression (P = 0.031), whereas CRP and sCD14 levels remained similar to pre-ART levels. At viral suppression, levels of the soluble markers did not correlate with each other. CD4+ T-cell counts pre-ART tended to modestly correlate with levels of D-dimer (r = 0.35; P = 0.058) and CRP (r = 0.33; P = 0.078). At 36 weeks after treatment interruption (week 72), D-dimer levels returned back to pre-ART levels. However, CD8+ T-cell activation was significantly lower than pre-ART levels (35.8% at week 0 vs 28.9% at week 72; P = 0.004).
Among the A5217 participants who started ART within the first 6 months of HIV infection, high levels of sCD14 and CRP remain similar to pre-ART levels, suggesting that immune damage occurring in the initial stages of infection persists despite short-term virologic suppression.
*Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA;
†Statistical and Data Analysis Center, Harvard T.H. Chan School of Public Health, Boston, MA;
‡Department of Medicine, University of California San Diego, San Diego, CA;
§Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; and
‖Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
Correspondence to: Bernard J. C. Macatangay, MD, University of Pittsburgh School of Medicine, S827 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261 (e-mail: firstname.lastname@example.org).
Supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI68636, and UM1 AI106701. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. This study was also supported by the National Institutes of Health grants AI43638 and AI69432.
The authors have no conflicts of interest to disclose.
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Received October 25, 2016
Accepted February 06, 2017