Coagulation and inflammatory biomarkers in children and adolescents with HIV

The Strategies for the Management of AntiRetroviral Therapy (SMART) trial has transformed HIV research by unambiguously demonstrating the link between viral replication, inflammation and clinical outcomes. A detailed sub-study in SMART found that, in adults, particular coagulation and inflammatory biomarkers (specifically D-dimer and IL-6) were very strongly associated with mortality risk, and levels of these biomarkers increased in association with HIV viral load when study participants interrupted ART. [1]

In the new issue of the journal AIDS, a group of Italian researchers describe results of a study designed to provide insight into whether the findings of SMART are relevant to children and adolescents with HIV. [2]

The researchers divided a cohort of 88 individuals (mean age 13.5 years) into high and low HIV viral load groups using a cut-off of 1,000 copies of HIV RNA/mL. Higher viral load levels were associated with significantly lower levels of protein S, a substance involved in blood coagulation; low levels of protein S are known to be associated with an increased risk of excessive blood clotting (thrombophilia). Levels of D-dimer were also significantly elevated in the high viral load group and showed a statistically significant correlation with HIV RNA levels (R2 0.37, P<0.001). D-dimer is a small protein fragment that is produced when blood clots are degraded in the body. Levels of C-reactive protein (CRP), which increased in SMART participants after ART interruption, showed no differences between the high and low viral load groups. IL-6 levels were not measured in this study.

In discussing their findings, the researchers state: The study, given the low mean age of the cohort, highlights the direct role of HIV replication on coagulation disorders excluding the possible confounding role of major known risk factors for thrombosis and CVD, like hypertension, diabetes, and history of clinical thrombotic event. Furthermore, our analysis took into account the putative confounding action of other factors associated with an increased risk of thrombosis and CVD disease both in the general population (smoke, age, dyslipidaemia), and HIV-infected population (cumulative use of cART and protease inhibitor, actual use of ABC and ddI, dyslipidaemia). Nevertheless the study has some limitations since it is a cross-sectional study and the power for analysis of all variables considered has been limited by the relative small amount of observations. Prospective studies are needed to confirm and investigate the clinical implications of our observations.

2. Pontrelli G et al. HIV is associated with thrombophilia and high D-dimer in children and adolescents. AIDS. 24(8):1145-1151, May 15, 2010. doi: 10.1097/QAD.0b013e328337b9a0.