Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death

David R. Boulware, Katherine Huppler Hullsiek, Camille E. Puronen, Adam Rupert, Jason V. Baker, Martyn A. French, Paul R. Bohjanen, Richard M. Novak, James D. Neaton, Irini Sereti

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200 Scopus citations

Abstract

Background. Substantial morbidity occurs during the first year of antiretroviral therapy (ART) in persons with advanced human immunodeficiency virus (HIV) disease despite HIV suppression. Biomarkers may identify high-risk groups. Methods. Pre-ART and 1-month samples from an initial ART trial were evaluated for biomarkers associated with AIDS events or death within 1-12 months. Case patients (n = 63) and control patients (n = 126) were 1:2 matched on baseline CD4 cell count, hepatitis status, and randomization date. All had ≥1 log10 HIV RNA level decrease at 1 month. Results. Case patients had more frequent prior AIDS events, compared with control patients (P = .004), but similar HIV RNA levels at baseline. Pre-ART and 1-month C-reactive protein (CRP), D-dimer, and interleukin 6 (IL-6) levels and pre-ART hyaluronic acid (HA) levels were associated with new AIDS events or death (P ≤ .01). Patients who experienced immune reconstitution inflammatory syndrome (IRIS) events had higher pre-ART tumor necrosis factor α (TNF-α) and HIV RNA levels and significant 1-month increases in CRP, D-dimer, IL-6, interleukin 8, CXCL10, TNF-α, and interferon-c levels, compared with patients who experienced non-IRIS events (P ≤ .03). Individuals with baseline CRP and HA levels above the cohortmedian (>2.1 mg/L and >50.0 ng/mL, respectively) had increased risk of AIDS or death (OR, 4.6 [95% CI, 2.0-10.3]; P < .001) and IRIS (OR, 8.7 [95% CI, 2.2-34.8] P = .002). Conclusions. Biomarkers of Inflammation (CRP, IL-6), coagulation (D-dimer), and tissue fibrosis (HA) measured pre-ART and at 1 month are associated with higher risk of AIDS events, IRIS, or death, warranting additional study as risk stratification strategies.

Original languageEnglish (US)
Pages (from-to)1637-1646
Number of pages10
JournalJournal of Infectious Diseases
Volume203
Issue number11
DOIs
StatePublished - Jun 1 2011

Bibliographical note

Funding Information:
This work was supported in part through the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health through grants U01AI042170, U01AI046362, and U01AI068641 for the FIRST Study (CPCRA 058) and INSIGHT, as well as through the Intramural Research Program of NIAID. In addition, this project has been supported in part by federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. D. R. B. is supported by NIAID grant K23AI073192-02, and J. V. B. by grant K12RR023247-05.

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