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

TLDR

Advanced HIV infection leads to substantial morbidity during the first year of ART even after viral suppression. The study evaluated pre‑ART and 1‑month biomarker levels to identify patients at high risk of AIDS events or death within 12 months of initiating ART. A matched case‑control design (63 cases, 126 controls) was used, matching on baseline CD4 count, hepatitis status, and randomization date, to assess these biomarkers. Higher pre‑ART and 1‑month levels of CRP, D‑dimer, IL‑6, and hyaluronic acid were associated with increased risk of AIDS events, death, or IRIS, with baseline CRP and HA above the cohort median conferring a 4.6‑fold higher odds of AIDS or death and an 8.7‑fold higher odds of IRIS.

Abstract

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.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 log(10) HIV RNA level decrease at 1 month.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-γ levels, compared with patients who experienced non-IRIS events (P ≤ .03). Individuals with baseline CRP and HA levels above the cohort median (>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).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.