Thromboinflammatory biomarkers and thrombotic risk in virologic failure and drug-resistant HIV: Emerging roles of d-dimer, fibrinogen, and coagulation dysregulation.

HIV infection that is highly resistant is marked by ongoing viral replication, long-lasting immune activation, endothelial activation, and a prothrombotic condition with heightened risk of thromboembolic complications. Elevated D-dimer and fibrinogen remain important indicators of fibrin formation, degradation, inflammation, and coagulation activation in this group. However, contemporary interpretation of these markers should also consider von Willebrand factor (VWF), tissue factor activity, and thrombin generation as mechanistic links between endothelial perturbation and intravascular clot formation. The molecular mechanisms behind these increases entail prolonged endothelial damage, release of VWF from Weibel-Palade bodies, heightened levels of pro-inflammatory cytokines such as IL-6, augmented tissue factor expression on monocytes and endothelial cells, and downstream thrombin generation that converts fibrinogen to fibrin. Simultaneously, fibrinolysis produces D-dimer fragments, acting as sensitive indicators of ongoing thrombogenesis. In individuals with drug-resistant HIV or virologic failure, these mechanisms are heightened, associating biomarker increases with greater risks of venous thromboembolism, cardiovascular events, stroke, and death. Assessing D-dimer and fibrinogen concentrations alongside endothelial and thrombin-generation biomarkers may provide valuable diagnostic and prognostic insight, facilitating early detection of patients with heightened thrombotic risk and guiding prompt clinical actions. Nevertheless, standardized guidelines for biomarker application in HIV-resistant populations remain limited, emphasizing the necessity for additional studies to confirm thresholds, elucidate mechanisms, and enhance management strategies to minimize morbidity and mortality linked to thrombotic complications.