Biomarkers of inflammation and coagulation predict non-AIDS-defining events in a prospective cohort of virologically suppressed people living with HIV.

Abstract

Objective: To assess the association between biomarkers of inflammation, coagulation and immune activation and the incidence of non-AIDS-defining events in a contemporary, antiretroviral therapy (ART)-experienced and virologically suppressed cohort of people living with HIV (PLWH).

Methods: Prospective, observational cohort study. PLWH aged 30-70 years, with undetectable HIV viral load and no history of cardiovascular disease, randomly selected from outpatients were included. At baseline, plasma biomarkers (high-sensitivity C-reactive protein [hs-CRP], sCD163, sCD14, D-dimer, interleukin-6, soluble vascular cell adhesion molecule [s-VCAM] and lipoprotein-associated phospholipase A2 [Lp-PLA2] activity) were measured. Non-AIDS-defining events (non-AIDS cancer and cardiovascular events) and non-AIDS death were recorded until November 2022. Cumulative incidence was analysed for each endpoint and adjusted Cox regression used to assess associations.

Results: A total of 438 participants were included: 81.1% men, mean age 50.4 (SD 10.1) years. The median time on treatment was 15.5 (interquartile range [IQR] 8.69; 19.7) years and with undetectable viral load 7.05 (IQR 4.03; 11.6) years. A total of 77 non-AIDS-defining events were recorded in 70 patients (38 non-AIDS cancers, 21 cardiovascular events, 37 non-AIDS deaths) in a median follow-up of 6.72 (IQR 6.02; 7.36) years. The cumulative incidence for non-AIDS cancer, cardiovascular event and non-AIDS death was 8.7% (95% CI 6.2-11.7), 4.79% (95% CI 2.99-7.24) and 8.47% (95% CI 6-11.5), respectively. In adjusted models, sCD163 was associated with incident non-AIDS cancer (hazard ratio [HR] 1.23, 95% CI 1.08-1.39), hs-CRP with incident cardiovascular events (HR 1.61, 95% CI 1.05-2.47), sCD163 (HR 1.28, 95% CI 1.11-1.46) and D-dimer (HR 1.75, 95% CI 1.08-2.86) with non-AIDS death.

Conclusions: Biomarkers of inflammation, monocyte activation and coagulation were associated with non-AIDS-defining events in a contemporary and long-term suppressed cohort of PLWH.